4

Blood Transfusions, Blood Alternatives

and Transfusion Reactions
A Guide to Transfusion Medicine
Fourth Edition

JL Callum, PH Pinkerton, A Lima, Y Lin

Sunnybrook Health Sciences Centre
K Karkouti, L Lieberman, JM Pendergrast
University Health Network
N Robitaille
CHU Sainte-Justine
AT Tinmouth
The Ottawa Hospital
KE Webert
Canadian Blood Services

Published by
 Preface to the Fourth Edition
Since 2001 the Ontario Ministry of Health and Long-Term Care (MOHLTC) has provided
funding and oversight for a variety of initiatives directed at promoting rational,
evidence-based use of blood components, derivatives and alternatives, and reduction
of transfusion errors. These included the publication of the First Edition of Bloody Easy
in 2003. As the field of Transfusion Medicine is rapidly changing with new evidence to
define acceptable practice, subsequent editions produced under the aegis of the Ontario
Regional Blood Coordinating Network (ORBCoN) in 2006 and 2011, reflected this
evolution.
The current Fourth Edition appears as two significant concepts are emerging in the
guidance of Transfusion Medicine practice. The first is the approach covered under
the rubric of “Patient Blood Management”, which is a discipline designed to optimize
patient care for patients who may require transfusion, based on the application of
evidence-based, multidisciplinary medical and surgical practices to integrate the best
use of transfusion and its alternatives and adjuncts1,2. The second is the initiative known
Copyright 2016, Ontario Regional Blood Coordinating Network as “Choosing Wisely®” promoted in the U.S. by the American Board of Internal Medicine
Foundation (ABIM) (www.abimfoundation.org), and in Canada by the Canadian Medical
All rights reserved. No part of this publication may be reproduced, stored Association (CMA) (www.choosingwiselycanada.org). “Choosing Wisely” seeks to
in a retrieval system or transmitted in any form or by any means, electronic, promote avoidance of wasteful or unnecessary tests, treatments and procedures.
mechanical, photocopying, recording, or otherwise, without prior permission An increasing weight of evidence from clinical trials is accumulating to support the
in writing from the copyright owner. clinical benefits of restrictive rather than liberal transfusion policies.

The content of this publication is that of the authors of the materials, papers, There are several significant changes from the Third Edition. The critical hemoglobin
publications, and proceedings. The editors and publishers do not assume any, levels to prompt consideration of red blood cell transfusion have been reduced in light
and disclaim all, liability for loss, injury, or damage arising from any use made of increasing confidence that these recommended levels for restricting transfusion are
of any information, instructions, ideas, and recommendations therein. not resulting in adverse consequences, and, indeed, may in some circumstances result in
improved patient outcomes3. A lack of evidence of clinical benefit from frozen plasma
First Edition, 2003. transfusion for mild-marginal coagulopathy as defined by the INR4,5,6 supports adoption
Second Edition, 2005 and 2006. of the “Choosing Wisely” recommendation that an INR of 1.8 or more should replace
Third Edition, 2011. the convention hitherto of 1.5 or more. In “Adverse Events”, there has been a decline in
Fourth Edition, 2016. transfusion transmitted infection and acute lung injury, offset by increasing recognition
of circulatory overload, particularly in patients with compromised cardiac function7.
Reference to obsolete practices such as acute normovolemic hemodilution and
autologous pre-surgical blood deposit have been removed. The introduction in
Library and Archives Canada Cataloguing in Publication Ontario of a mandatory request process for IVIG for infusion8 is intended to reduce
inappropriate use of IVIG (about 25-30% of Canadian Blood Services annual budget
Callum, J. L. (Jeannie L.), 1967-, author Bloody easy 4 : blood transfusions, is for IVIG). A pre-transfusion checklist for physicians (for RBC transfusion orders) has
blood alternatives and transfusion reactions / J.L. Callum [and eight others]. been placed on the back cover (for easy access) to help promote safe ordering practices
– Fourth edition. to reduce the risk of transfusion complications. Finally, a section on the use of
Rh immunoglobulin has been added. This and previous editions of Bloody Easy would
Previously published: Bloody easy 3 / J.L. Callum. ISBN 978-0-9869176-2-2
have been impossible without the dedication, attention to detail and patience of
(paperback)
Stephanie Cope, ORBCoN Central Office.

1. Blood--Transfusion. I. Ontario Regional Blood Coordinating Network,

issuing body II. Title. III. Title: Bloody easy four.

RM171.C333 2016 615.3'9 C2016-904318-5

2 3
 Ten Things Physicians and
Patients Should Question9,10
4 Don’t routinely transfuse platelets for patients
with chemotherapy-induced thrombocytopenia
if the platelet count is greater than 10 x 109/L
Don’t transfuse blood if other
1 non-transfusion therapies or
in the absence of bleeding.
A platelet count of 10 x 109/L or greater usually
observation would be just as effective. provides adequate hemostasis. Platelet transfusions
Blood transfusion should not be given if other are associated with adverse events and risks.
safer non-transfusion alternatives are available. Considerations in the decision to transfuse platelets
For example, patients with iron deficiency without include the cause of the thrombocytopenia,
hemodynamic instability should be given iron comorbid conditions, symptoms of bleeding, risk
therapy. factors for bleeding, and the need to perform an
invasive procedure.
2 Don’t transfuse more than one red cell unit
at a time when transfusion is required in
stable, non-bleeding patients. 5 Don’t routinely use plasma or prothrombin
complex concentrates for non-emergent
Indications for red blood cell transfusion depend reversal of vitamin K antagonists.
on clinical assessment and the cause of the anemia. Patients requiring non-emergent reversal of
In a stable, non-bleeding patient, often a single warfarin can often be treated with vitamin K or by
unit of blood is adequate to relieve patient discontinuing the warfarin therapy. Prothrombin
symptoms or to raise the hemoglobin to an complex concentrates should only be used for
acceptable level. Transfusions are associated with patients with serious bleeding or for those who
increased morbidity and mortality in high-risk need urgent surgery. Plasma should only be used
hospitalized inpatients. Transfusion decisions in this setting if prothrombin complex concentrates
should be influenced by symptoms and hemoglobin are not available or are contraindicated.
concentration. Single unit red cell transfusions
Don’t use immunoglobulin therapy for
should be the standard for non-bleeding,
hospitalized patients. Additional units should
6 recurrent infections unless impaired antibody
only be prescribed after re-assessment of the responses to vaccines are demonstrated.
patient and their hemoglobin value. Immunoglobulin (gammaglobulin) replacement
does not improve outcomes unless there is
3 Don’t transfuse plasma to correct a mildly
elevated (<1.8) international normalized ratio
impairment of antigen-specific IgG antibody
responses to vaccine immunizations or natural
(INR) or activated partial thromboplastin time infections. Isolated decreases in immunoglobulins
(aPTT) before a procedure. (isotypes or subclasses), alone, do not indicate a
A mildly elevated INR is not predictive of an need for immunoglobulin replacement therapy.
increased risk of bleeding. Furthermore, transfusion Exceptions include genetically defined/suspected
of plasma has not been demonstrated to disorders. Measurement of IgG subclasses is not
significantly change the INR value when the routinely useful in determining the need for
INR was only minimally elevated (<1.8). immunoglobulin therapy. Selective IgA deficiency
is not an indication for administration of
immunoglobulin.

4 5
 7 Don’t order unnecessary pre-transfusion testing
(type and screen) for all pre-operative patients. 9 Don’t transfuse O negative blood except to
O negative patients and in emergencies for
Pre-operative transfusion testing is not necessary female patients of child-bearing potential
for the vast majority of surgical patients (e.g., of unknown blood group.
appendectomy, cholecystectomy, hysterectomy Males and females without childbearing potential
and hernia repair) as those patients usually do can receive O Rh-positive red cells. O-negative red
not require transfusion. Ordering pre-transfusion cell units are in chronic short supply, in some part
testing for patients who will likely not require due to over utilization for patients who are not
transfusion will lead to unnecessary blood drawn O-negative. To ensure O-negative red cells are
from a patient and unnecessary testing performed. available for patients who truly need them, their
It may also lead to unnecessary delay in the surgical use should be restricted to: (1) patients who are
procedure waiting for the results. To guide you O-Rh-negative; (2) patients with unknown blood
whether pre-transfusion testing is required for a group requiring emergent transfusion who are
certain surgical procedure, your hospital may have female and of child-bearing age. Type specific red
a maximum surgical blood ordering schedule or cells should be administered as soon as possible in
specific testing guidelines based on current surgical all emergency situations.
practices.
10 Don’t transfuse group AB plasma to non-group
8 Don’t routinely order perioperative
autologous and directed blood collection.
AB patients unless in emergency situations
where the ABO group is unknown.
There is no role for routine perioperative The demand for AB plasma has increased. Group
autologous donation or directed donation except AB individuals comprise only 3% of Canadian
for selected patients (for example, patients with blood donors. Those donors who are group AB
rare red blood cell antigen types). Medical evidence are universal donors for plasma, thus are the
does not support the concept that autologous most in-demand type for plasma transfusion.
(blood donated by one’s self) or directed blood Type-specific plasma should be issued as soon as
(blood donated by a friend/family member) is possible in emergency situations to preserve the
safer than allogeneic blood. In fact, there is concern AB plasma inventory for those patients where
that the risks of directed donation may be greater the blood group is unknown.
(higher rates of positive test results for infectious
diseases). Autologous transfusion has risks of
bacterial contamination and clerical errors (wrong
unit/patient transfused). As well, autologous
blood donation before surgery can contribute
to perioperative anemia and a greater need for
transfusion.

6 7
 C O N T E N T S

Important Notes 1 Transfusion Basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10-16

u This booklet is an educational tool to assist in 2 Red Blood Cell Basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18-27
providing care to patients.
3 Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28-41
u The recommendations do not replace the need • Platelets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
to consult an expert in transfusion medicine. • Frozen plasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
• Cryoprecipitate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
u These recommendations should not be applied
rigidly, since they could result in some patients 4 Risk Charts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42-45
u Physician risk chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
receiving unnecessary transfusions or experiencing
u Patient risk chart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
adverse effects from under-transfusion.
5 Transfusion Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46-82
u Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
u Reaction by symptom . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Disclaimer: While the advice and information in these guidelines are
• Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
• Dyspnea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
believed to be true and accurate at the time of publishing, neither
• Urticaria & other allergic reactions/anaphylaxis . . . . . . . . . . . . . . 62
the authors nor the publishers accept any legal responsibility or
• Hypotension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
liability for any errors or omissions in the information provided, or • Hemolysis after transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
for any of the recommendations made. Any decision involving patient • Cytopenias after transfusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
care must be based on the judgement of the attending physician • Virus, parasite and prion infections . . . . . . . . . . . . . . . . . . . . . . . . 74
according to the needs and condition of each individual patient. • Complications of massive transfusion . . . . . . . . . . . . . . . . . . . . . . . 78
• Postpartum Hemorrhage (PPH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

6 Blood Conservation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84-97

u Good surgical technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
u Stopping antiplatelet and anticoagulants . . . . . . . . . . . . . . . . . . . . . . 86
u Iron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
u Intraoperative cell salvage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
u Erythropoietin in elective surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
u Antifibrinolytics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
u DDAVP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
u Regional anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
u Topical agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
u Other blood conservation strategies . . . . . . . . . . . . . . . . . . . . . . . . . . 97

7 Erythropoietin and Medical Patients . . . . . . . . . . . . . . . . . . 98-101

u Chronic Renal Failure (CRF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
u Anemia associated with malignancy . . . . . . . . . . . . . . . . . . . . . . . . . 101

8 Fractionated Blood Products . . . . . . . . . . . . . . . . . . . . . . . 102-129

u Albumin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
u IVIG and SCIG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
u Prothrombin Complex Concentrates (PCC) . . . . . . . . . . . . . . . . . . . . 124
u RhIG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

9 Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130-143

10 Appendices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144-161
u Appendix A: Price list . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144
u Appendix B: Information for physicians treating
patients who are Jehovah’s Witnesses . . . . . . . . . . . . . . . . . . . . . . . . 145
u References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146
8 9
 Transfusion Basics
A Overview

Who regulates n Donor units tested for:

n Health Canada regulates blood collection,
testing, processing, and distribution. DONOR UNITS SPECIFIC AGENTS TESTS USED
TESTED FOR:
n Health Canada Blood Regulations require
Blood groups ABO and Rhesus (Rh) D Blood group serology
hospitals to follow the national standard
Red cell alloantibodies
(see below) (http://laws-lois.justice.gc.ca/
eng/regulations/SOR-2013-178/). Viruses HIV 1 and 2 Antibody and nucleic acid testing
n Health Canada provides guidance to Hepatitis B Surface antigen, core antibody
assist hospitals in complying with the and nucleic acid testing
blood regulations (http://www.hc- Hepatitis C Antibody and nucleic acid testing

Red Blood
Cell Basics
sc.gc.ca/dhp-mps/brgtherap/applic- HTLV I and II Antibody testing
demande/guides/blood-reg-sang/blood- West Nile Virus Nucleic acid testing (seasonal)
guid-sang-ligne-2014-10-23-eng.php).
Bacteria Syphilis Serology
Bacterial contamination Bacterial culture (Platelets only)

National Standard Parasites Chagas Disease Antibody testing

n Canadian Standards Association (CSA Group) (at risk donors only)
publishes the national standard for all
aspects of blood management (current n All whole blood and apheresis donors
version, CAN/CSA -Z902-15, available at at CBS and HQ are unpaid volunteers.
http://shop.csa.ca/). n Plasma for fractionation is screened for
n Canadian Society for Transfusion parvovirus B19 by nucleic acid testing.

Components
Medicine (CSTM) publishes standards for
Hospital Transfusion Services. These
standards are consistent with the CSA Whole blood processing
national standard (www.transfusion.ca).
n Collect 500 mL whole blood.
n Divert the first 40 mL to reduce risk of
300 mL 350 mL
Who collects bacterial contamination from donor skin;
n Canadian Blood Services (CBS), the 40 mL are used for donor unit testing.
in all provinces and territories n Blood is centrifuged and separated into
except Québec. three parts:
n Héma-Québec (HQ) in Québec. u Red Blood Cells

u Plasma

u Buffy coat 10 mL 290 mL

Donor screening n The Buffy coat units from four donors

n Donors are screened using: are combined with one plasma unit and
u donor questionnaire further processed to separate the platelets.
u donor vital signs (temperature, n The red blood cell and platelet components
heart rate, blood pressure) are leukoreduced.
u donor hemoglobin

10 11
 Transfusion Basics
T R A N S F U S I O N B A S I C S

Whole blood processing (cont’d) Process for Preparing Blood Components from Donated Units
n Certain groups of patients need
Step 1 - Whole Blood Separation
irradiated blood components to prevent
transfusion-associated graft vs host Plasma Plasma

disease (TA-GvHD).
n CBS and HQ provide irradiated products Buffy
Buffy Coat
on demand. cent
rifuged @ 20°C
Coat

u Refer to TA-GvHD (see page 71) for list

of patient groups that need irradiated

RBC RBC
blood

Step 2 - RBC Additive

Red Blood
Cell Basics
B Red Blood Cells and Components:
Storage Conditions and Volumes11 RBC
Leukoreduced
RBC &
RBC
COMPONENT APPROX. STORAGE STORAGE PRE-TRANSFUSION Additive
VOLUME LIMIT TEMP. PREPARATION TIME*
Leukoreduction
Red blood cells 300 mL 42 days 1-6 °C 10-45 minutes
Buffy coat 350 mL 5 days 20-24 °C 5 minutes Step 3 - Plasma
derived platelets Female
(from 4 units) Plasma
Fractionation to manufacture albumin and IVIG

Apheresis 330 mL 5 days 20-24 °C 5 minutes

platelets

Components
Plasma For Transfusion

Plasma
Frozen plasma 290 mL 1 year -18 °C or colder 30 minutes Male
Cryo-
Plasma
super-
Apheresis plasma 500 mL 1 year -18 °C or colder 30 minutes natant

Cryoprecipitate 10 mL 1 year -18 °C or colder 30 minutes Plasma

Frozen at - 18°C

*In addition to the 45 minutes required for pre-transfusion specimen testing Cryo-
precipi-
tate

HQ provides buffy coat Please see Circular of Information,

platelets from 5 units Canadian Blood Services Step 4 - Buffy Coat Platelet
of buffy coat. HQ (www.blood.ca/en/hospitals/circular-
storage limit for information) or Circular of Information, Male
platelets is 7 days. Hema-Quebec (http://www.hema- Plasma
quebec.qc.ca/userfiles/file/media/anglais/
publications/SPE-00176%5B3%5D_C16075_ 4 Platelet
LIVRET_HEMA_ANG_web.pdf) for most Buffy Coats
up-to-date information.

Leuko-
reduced
Pool
Buffy Coat
Platelets

Leukoreduction

12 13
 Transfusion Basics
T R A N S F U S I O N B A S I C S

C Informed Consent D Directed Blood Donations

A requirement for transfusion consent is What

identified as an important priority element n Directed blood donations are units C H O O S E W I S E L Y
to be incorporated into Patient Blood donated for a specific transfusion Directed blood donations
Management Programs.12 recipient. are only indicated in RARE
circumstances and should
When Who not be collected for routine
n Discuss the option of a transfusion n Currently in Canada, directed blood surgical procedures or for
early enough to allow for a blood A T T E N T I O N
donations are only recommended routine top-up transfusions
alternative(s) to be considered according
to the principles of patient blood
Refer to pages 42-44 for risk
charts, to assist discussion
! for patients with rare blood cell types. in premature neonates.

Red Blood
Cell Basics
management.12 of risks with patients. Where
n Directed blood donations are collected
What 13 by CBS and HQ.
n Include in your discussion:
u Description of blood or blood product Of note
n Directed blood donations transfused to
u Benefits
family members must be irradiated to
u Risks
prevent TA-GvHD.
u Alternatives
n Presently, there are no data to support
n Give your patient the opportunity to the concept that directed donors are
ask questions. safer than volunteer donors.
n Directed blood donation programs are

Components
Of note
n
logistically complicated to administer
Confirm that you discussed consent
and financially more expensive than
with the patient, by noting it in the Pediatrics volunteer donor programs.
patient’s chart.
n Complete the informed consent n For children
documentation as required at your without decision-
hospital. making capability,
n If transfusion is required, clearly the parent or legal
document the reason in the patient’s guardian must give
chart. informed consent.
n n Teenagers with
In the special case of Jehovah’s Witnesses,
helpful advice may be obtained from decision-making
their Hospital Information Services capability should
24 hours a day at 1-800-265-0327 give informed
(see Appendix B, page 143). consent themselves.
The age at which
teenagers can give
informed consent
varies from province
to province. Refer
to provincial
legislation.

14 15
 Transfusion Basics
T R A N S F U S I O N B A S I C S

E Clinical Practice Guidelines

Red Blood Cells14 n Female children and females of child-

n The American Association of Blood bearing age/potential who are Rh(D)
Banks (AABB) recommends adhering negative should probably receive Rh
to a restrictive transfusion threshold in immunoglobulin before, after or within
which the transfusion is not indicated 72 hours of receiving an Rh(D) positive
until the hemoglobin level is 70 g/L in platelet component.
hospitalized adult patients who are n Males and females who are not of
hemodynamically stable, including child-bearing potential who are Rh(D)
critically ill patients. negative and are transfused with Rh(D)
n The AABB recommends a restrictive positive platelet components probably

Red Blood
Cell Basics
RBC transfusion threshold of 80 g/L do not require Rh immunoglobulin.
for patients undergoing orthopedic
surgery, cardiac surgery and those
with pre-existing cardiovascular disease.
n They also state: “The restrictive
transfusion threshold of 70 g/L is
likely comparable with 80 g/L, but
RAC evidence is not available for all
categories of patients.”

Platelets15,16
n Prophylactic platelet transfusion

Components
should be given to patients with
hypoproliferative thrombocytopenia
when the platelet count is 10 x 109/L
or less.
n For elective central venous catheter
placement, a threshold of less than
20 x 109/L is recommended for
prophylactic transfusion.
n For elective diagnostic lumbar puncture,
a threshold of less than 50 x 109/L is
recommended for prophylactic
transfusion.
n For major elective non-neuraxial surgery,
a threshold of less than 50 x 109/L is
recommended for prophylactic
transfusion.

16 17
 Transfusion Basics
R E D B L O O D C E L L B A S I C S

A When and How to Order Tests B Routine Transfusion Medicine Tests

A T T E N T I O N TEST TIME (MIN) INFORMATION

1. Transfusion MIGHT 1. Transfusion
occur during PLANNED Uncrossmatched blood

!
ABO group 5 Patient RBCs tested for A and B antigen.
admission is required if the clinical
2. Surgery with state precludes waiting Rh (D) group 5 Patient RBCs tested for D antigen.
2. Surgery with >30% risk of for antibody screen and
>10% risk of transfusion crossmatch (45 minutes). Antibody 45 Screens for RBC alloantibodies formed as
transfusion Screen a result of prior transfusion or pregnancy.

CHOOSE WISELY Antiglobulin 45 Mandatory for patients with RBC

Crossmatch alloantibodies. Involves incubation of donor
Group & Screen Group & Screen & The following surgeries
RBCs, recipient plasma/serum, and anti-IgG.

Red Blood
Cell Basics
Crossmatch should have a
transfusion rate of
Immediate 5 Testing involves mixing of donor RBCs and
<10% and do not Spin
GROUP recipient plasma/serum. Used to verify ABO
require a group and Crossmatch compatibility only.*
screen: appendectomy,
ABO group
radical prostatectomy, Computer 2 Computer selects appropriate unit (donor
Rh (D) group transurethral resection Crossmatch units must have been re-tested to confirm ABO
of the prostate (TURP), group and recipient specimen must be tested
SCREEN hernia repair, single twice). Used to verify ABO compatibility only.*
knee replacement,
Antibody Screen primary total hip
replacement, Note: For centers using immediate spin or computer crossmatch,
CROSSMATCH laparoscopic crossmatching red cell units in advance of transfusion/surgery is

Components
rarely required unless antibody screen is positive.
cholecystectomy,
Antiglobulin Crossmatch OR
isolated laminectomy,
upper limb surgery and * For patients with a negative antibody screen and no history of
Immediate Spin Crossmatch OR
vaginal hysterectomy. RBC alloantibodies.
Computer Crossmatch

Pediatrics
n For infants less than 4 months of age, initial testing must
include ABO and Rh(D) group and an antibody screen,
using either a specimen from the infant or mother.
n If an unexpected RBC alloantibody is detected in the infant’s or
mother’s specimen, it is required that the infant receive RBC units
lacking the corresponding antigen(s) or units compatible by
antiglobulin crossmatch.
n This regimen should continue until the maternal antibody is no
longer detected in the infant’s specimen.

18 19
 Transfusion Basics
R E D B L O O D C E L L B A S I C S

C Checking Identity of Patient Recommended IV access

BLOOD COMPONENT/PRODUCT IV ACCESS
You must accurately identify the
Red blood cells – rapid transfusions in adults 16-18G (Gauge)
patient at the following times…
1. When collecting a blood specimen: Red blood cells – routine transfusions in adults 20-22G
u Accurately label each specimen
Other blood components/products Any size is adequate
BEFORE leaving the patient’s bedside
Pediatrics 22-25G
2. BEFORE beginning the transfusion,
All components and products – adults Central venous access
two clinical team members must: and pediatrics devices (CVAD)
u Verify the patient’s identity, by checking

Red Blood Cells

the name, date of birth and unique
identifier (e.g., hospital file number) Storage
n Only store RBCs in a temperature-
on their wristband against the
identification on the blood component controlled refrigerator with continuous
label before transfusing, and, where temperature monitoring by the
possible, also by verbal confirmation. transfusion service.
For example, ask: “What is your n Freezing or overheating blood may cause
name?” or “What is your date of hemolysis, and may harm the patient.
birth?”
u It is also important to ensure the
Monitor patient
n Check patient’s vital signs:
correct component type is being
u prior to starting each unit
transfused by checking the physician
order u 15 minutes after starting

Components
u at end of transfusion
A T T E N T I O N
u during any transfusion reactions

n
Check the patient’s wristband

!
before transfusing!
Transfuse slowly (50 mL/hr) for the
first 15 minutes, where appropriate.
Failure to check is the major
n Monitor the patient closely for the first
cause of acute hemolytic
15 minutes.

!
transfusion reactions.
A T T E N T I O N
Monitor patient closely
Pediatrics 11,13 for first 15 minutes.
For pediatric patients, transfuse
D Monitoring & Infusion Practices
slowly (1 mL/kg/h, up to
50 mL/h) for the first 15
How minutes. Usual administration
n RBCs must be transfused through a blood rate is 5 mL/kg/h, up to
administration filter (170-260 microns). 150 mL/h.
n RBCs are compatible ONLY with normal
saline.

20 21
 Transfusion Basics
R E D B L O O D C E L L B A S I C S

D Monitoring & Infusion Practices (cont’d) F Indications for RBCs

!
Transfuse A T T E N T I O N Acute blood loss ACUTE BLOOD LOSS &
n In non-urgent/non-bleeding/inpatient n Maintain hemoglobin >70 g/L during ANEMIA IN CRITICAL CARE
Transfuse one
settings red blood cells should be unit at a time. active bleeding.18
transfused during daytime hours (for u Consider rate of bleeding, hemodynamic
patient safety) and transfused one unit factors, evidence of tissue ischemia,
at a time. institutional speed of blood
n

!
Assess patient prior to ordering another A T T E N T I O N delivery/laboratory testing in decision
unit. about transfusion
n
Infuse each unit over
Expect a 10 g/L increase in hemoglobin u Ensure prompt blood availability when

Red Blood Cells

2 hours, maximum 4 hours.
in the non-bleeding adult patient. hemoglobin is <80 g/L
n Each unit is usually infused over 2 hours, n Consider maintaining a higher
but always within 4 hours of issue from hemoglobin level (>80 g/L) for

!
blood bank. A T T E N T I O N patients with:
n Consider a slower rate for patients at risk Consider a slower rate u Unstable or acute coronary syndromes 19

of circulatory overload and refer to for patients at risk of u Coronary artery disease20
prevention on page 61. circulatory overload.
u Uncontrolled/unpredictable bleeding
n
n
In massive transfusion, blood should only
Liberal transfusion practices (hemoglobin
be warmed using an approved blood
>90 g/L) in the setting of gastrointestinal
warming device.
hemorrhage results in a higher rate of
re-bleeding and mortality.21

Components
Anemia in critical care and coronary care
Pediatrics n Consider a transfusion when the C H O O S E W I S E L Y
Dosage: patient’s hemoglobin is less than 70 g/L.22
n A transfusion of 10 mL/kg
Don't transfuse RBCs
n Post-cardiac surgery, there is no benefit to an asymptomatic,
of RBC stored in an additive to a liberal transfusion strategy (when non-bleeding, inpatient
solution is expected to raise 75 g/L was compared to 90 g/L there with a hemoglobin level
the hemoglobin level by was no difference in 30-day mortality).23 above 70 g/L!
n
approximately 10 g/L.17
In a patient with an acute coronary
syndrome, there is controversy over
where to maintain the hemoglobin
E Ordering RBCs level.14
u There are insufficient data to

n recommend maintaining the

!
If the patient is not adequately volume
A T T E N T I O N
resuscitated, the hemoglobin value may hemoglobin above some arbitrary
be spuriously high OR, in the setting of Record the order in the level
over hydration, spuriously low. correct patient’s chart. u Consider transfusing if there are clear

n A falsely low hemoglobin value may result signs of inadequate tissue oxygen
if test specimen are taken near a site of IV delivery in a patient with a low
infusion. hemoglobin and an acute coronary
n Certain patients require irradiated products. syndrome
Refer to page 71.

22 23
 Transfusion Basics
R E D B L O O D C E L L B A S I C S

F Indications for RBCs (cont’d)

!
Unnecessary phlebotomy for laboratory A T T E N T I O N
testing is a major contributor to anemia Pediatrics
Minimize blood work as
in a critically ill patient. Anemia in neonatal critical care
it contributes to need for
n Except for patients with unstable coronary n Several guidelines for small-volume RBC transfusions for
transfusion in critical care.
artery syndromes, a restrictive transfusion newborns have been published in the last decade.26,27,28,29
policy (trigger hemoglobin 70 g/L) has n Two recent randomized controlled trials came to differing
proved at least as effective as a liberal conclusions regarding whether a restrictive strategy was as
transfusion policy for critically ill patients.22,24 safe as a liberal strategy.30,31
n Recombinant erythropoietin reduces the n Attention must be drawn to phlebotomy for laboratory

Red Blood Cells

risk of transfusion in critically ill patients testing since it is a significant cause of anemia in neonates.32
but does not improve mortality, and its n Expert recommendations for transfusion thresholds have
use is associated with an increased rate been published and are shown in the table below.33
of thrombotic events.25
RESPIRATORY AGE OF HEMOGLOBIN
STATUS NEONATE THRESHOLD
Pediatrics
Anemia in pediatric critical care Ventilated Age <1 week Hgb <120 g/L
n In children whose condition is Age >1 week Hgb <110 g/L
stable in the ICU, a transfusion On 02/CPAP Age <1 week Hgb <100 g/L
is not usually required unless Age >1 week Hgb <90 g/L
Hgb ≤75 g/L
the patient’s hemoglobin is
less than 70 g/L. Stable and off 02 Age >1 week

Components
n A restrictive transfusion strategy
(trigger hemoglobin 70 g/L) was n Delayed cord clamping in premature neonates reduces
proven to be as safe as a liberal morbidity including risk of transfusion.34
transfusion strategy (95 g/L).24
u This recommendation may not be

applicable to neonates under 28 days

old, children with severe hypoxemia,
hemodynamic instability, active
blood loss or cyanotic heart disease
as these groups were excluded from
this clinical trial

24 25
 Transfusion Basics
R E D B L O O D C E L L B A S I C S

F Indications for RBCs (cont’d)

Perioperative patients CHOOSE WISELY Chronic anemia 39,40

n Manage patients undergoing elective n Administer transfusions only when
Before recommending red
surgery preoperatively, intraoperatively, and blood cell transfusion for alternatives do not exist or have failed.18
postoperatively with strategies to minimize the management of n Administer RBCs at intervals to maintain
the need for RBCs18 (see pages 86-96). anemia, the possibilities the hemoglobin just above the lowest
n Administer RBCs one unit at a time for reversal of anemia by concentration that is not associated with
in non-urgent settings.35,36 non-transfusion treatment symptoms of anemia.18
n Assess patient prior to transfusing should be thoroughly
n Assess patients that are expected to have
examined.
additional units (clinical exam and long-term transfusion dependent survival
hemoglobin level).35 for iron overload.

Red Blood
Cell Basics
n

!
For orthopedic patients with A T T E N T I O N n Chelation therapy should be considered
cardiovascular disease, post-operative RBCs: in patients who are iron-overloaded,
transfusion for symptomatic anemia or One unit at a time. transfusion dependent, and who have
hemoglobin of less than 80 g/L does not a life expectancy of more than one year.
increase adverse outcomes or delay n Iron overload is typically present after
recovery compared to a transfusion 20 units of RBCs (patients with a significant
trigger of 100 g/L.37 component of ineffective erythropoiesis
n Follow guidelines for perioperative patient: and upregulation of iron absorption may
become iron overloaded more quickly).
n
HEMOGLOBIN RECOMMENDATION
Monitor serum ferritin and transferrin
>90 g/L Likely inappropriate except in exceptional circumstances. saturation: tissue iron overload is likely

Components
if ferritin >1,000 ug/L and transferrin
70-90 g/L Likely to be appropriate if there are signs or symptoms saturation >75%.39
of impaired oxygen delivery (e.g., tachycardia, n Desferrioxamine, deferasirox, and
hypotension, cardiac ischemia, syncope, pre-syncope). deferiprone are available agents for iron
chelation, with target ferritin between
<70 g/L Likely to be appropriate. 500 and 1,000 ug/L, and appropriate
monitoring for drug toxicity (refer to
<60 g/L Transfusion recommended38 package insert).
u Young patients with low risk of ischemic cardiovascular
disease can sometimes tolerate greater degrees of anemia.
u Patients with chronic iron deficiency may often be better
managed with IV or PO iron alone. (PO iron works very
well in children with iron deficiency anemia and Hgb level
as low as 30 g/L in the absence of concerning symptoms
of anemia and assurance of reliable follow-up.)

26 27
 Transfusion Basics
C O M P O N E N T S : Platelets

A Basics

n Platelets come in 3 forms: What

u Pool of 4 units of buffy coat derived n ABO/Rh-identical platelets are
platelets (pools of 5 in Québec) preferred, but ABO/Rh non-identical
u Single donor (collected by apheresis) platelets may be transfused when
u HLA-matched single donor (for patients
ABO/Rh-identical platelets are not
available.
with HLA-alloimmunization and refractory
n Rh negative females of childbearing
to random donor platelets)
n
potential require Rh immunoglobulin
In non-bleeding patients, the risk of
(RhIG) when Rh positive platelets are
spontaneous hemorrhage is low when
transfused to avoid formation of
platelet count is greater than 10 x 109/L.

Red Blood
Cell Basics
anti-D antibody.
n In Canada, all platelet products are tested u Each platelet pool contains up to
for bacterial contamination which lowers
0.5 mL of RBCs42
but does not eliminate the risk of sepsis.
u Each 120 ug of RhIG covers 12 mL
n Platelet transfusions may be associated with CHOOSE WISELY
whole blood (6 mL RBC) and lasts
higher odds of arterial thrombosis and Platelet transfusions are approximately 21 days
mortality among TTP and HIT patients.41 rarely required for n RhIG is not recommended for males,
patients with ITP except
and females of non-childbearing
for the management
potential, because risk of immunization
of life-threatening
hemorrhage!
from platelets is low (about 1%) and
passive anti-D complicates compatibility

Components
testing and may delay transfusion.43
B Monitoring & Infusion Practices INFUSION Storage
n Platelets must be stored at 20-24 ºC
How (room temperature) with constant
n Buffy coat derived pooled platelets from mixing to preserve platelet function.
multiple donors or single donor apheresis n

!
Do not refrigerate. Inadvertently A T T E N T I O N
platelets are supplied. “chilled” platelets will be rapidly
n Platelets must be transfused through cleared by hepatic macrophages.
Do NOT put platelets
a blood administration filter (170-260 in red cell coolers or
in the refrigerator.
microns).
n Fresh blood administration filter preferred. Pediatrics
n
Dose: 26,27
Platelets are compatible ONLY with normal
n Children and neonates:
saline.
10 mL/kg up to a maximum
of 1 pool of platelets.

28 29
 Transfusion Basics
C O M P O N E N T S : Platelets

B Monitoring & Infusion Practices (cont’d) PLATELET REFRACTORINESS MANAGEMENT ALGORITHM 44,46

Post-transfusion increment in platelet count <7.5 x 109/L

Monitor patient
n Check patient’s vital signs:
u prior to starting No Yes
u 15 minutes after starting

u at end of transfusion
Refractoriness not present Use ABO identical platelets
u during any transfusion reactions

n Transfuse slowly (50 mL/hr) for the first

15 minutes, where possible. Continue use of pooled Platelet count increment
n
donor platelets <7.5 x 109/L
Monitor the patient closely for the first

Red Blood
Cell Basics
15 minutes especially for signs of bacterial

!
sepsis. A T T E N T I O N Monitor post-transfusion
n Each dose of platelets should increase platelet count Yes No
Monitor patient closely
the patient’s platelet count at 1 hour
for first 15 minutes.
by at least 15-25 x 109/L.44
Consider, and where present, manage
other causes of refractoriness.
Transfuse If absent, test for HLA antibodies
n Recommended infusion time is 60 minutes
per dose (maximum infusion time 4 hours).
Antibodies present

Components
Follow-up
n
Yes No
Outpatients with hypoproliferative
thrombocytopenia should have a
post-transfusion platelet count every
3-5 platelet transfusions to ensure early Determine Continued poor
detection of HLA-alloimmunization. patient’s responses
HLA type
n Obtain post-transfusion platelet counts
(10-60 minutes) after infusion if patient
suspected to be refractory (poor increments
at 24 hours) to ensure adequate replacement Select HLA- Yes No
compatible
and recognition of platelet refractoriness.45
apheresis donor
u A platelet increment of <7.5 x 109/L
and supply single
suggests refractoriness and requires donor irradiated
investigation44 platelets
n If increments in platelet count are NOT
adequate, special measures are required.
Refer to the algorithm on page 31. Post-transfusion Seek transfusion
increment in medicine
platelet count consultation*
>7.5 x 109/L
* Consult Blood Centre physician
where no hospital transfusion
medicine physician available. Yes No
30 31
 Transfusion Basics
C O M P O N E N T S : Platelets

C Indications & Infusion Recommendations

Pediatrics – Platelet Transfusion Guidelines for Neonates

PLT (x 109/L) CLINICAL SETTING SUGGEST PLATELET CLINICAL INDICATION DOSE COLUMN
COUNT (x 109/L)
<10 Non-immune Transfuse 1 pool
thrombocytopenia of platelets45 <20 Term infants53 10 mL/kg
<10 Non-immune thrombocytopenia Transfuse 1 unit <30 Pre-term >7 days old53 10 mL/kg
& HLA-alloimmunized of HLA-matched Neonatal Alloimmune
apheresis platelets45

Pre-term and ≤7 days old53,55

Thrombocytopenia53,54

Red Blood
Cell Basics
<20 Procedures not associated with Transfuse 1 pool <50 10 mL/kg
significant blood loss (e.g., central of platelets15
Pre non-neuraxial surgery55
line placement)
Concurrent coagulopathy53,55
20-50 Procedures not associated with 1 pool of platelets on
Previous significant hemorrhage
significant blood loss hold, transfuse only if
(i.e., grade 3-4 intraventricular or
significant bleeding38
pulmonary hemorrhage)55
<30 Patient on anticoagulants that Transfuse 1 pool of Active Bleeding55
should not be stopped platelets
<100 Pre neuraxial surgery55 10 mL/kg
<50 Epidural anesthesia and lumbar Transfuse 1 pool
puncture immediately before CHOOSE WISELY
procedure 15,47

Components
Don't transfuse platelets in the following
<50 Procedures associated with Transfuse 1 pool situations:
blood loss or major surgery immediately before u Platelet count above 10 x 109/L with
(>500 mL expected blood loss) procedure 38,48 no bleeding in anticipation of a drop
to less than 10 x 109/L
<50 Immune thrombocytopenia Transfuse platelets
u For patients with ITP without major
only with life-
hemorrhage, even when platelet
threatening bleeding49
count <10 x 109/L
<100 Pre-neurosurgery or head trauma Transfuse 1 pool u For patients undergoing procedures
of platelets50,51 more than 6 hours later (give as close
to procedure as feasible)
Any Platelet dysfunction and marked Transfuse 1 pool u For minor procedures with platelet
bleeding (e.g., post cardiopulmonary of platelets38,52 counts >20 x 109/L (e.g., paracentesis
bypass). Exception: Transfusing or thoracentesis)
platelets for intracranial hemorrhage
not requiring surgical management
in patients on antiplatelet agents
leads to increased morbidity

!
A T T E N T I O N
The transfusion of platelets to non-operative
patients with ICH on ASA/clopidogrel
increases the risk of disability at 3 months.

32 33
 Transfusion Basics
C O M P O N E N T S : FP rl a
o tzeelne tPs l a s m a

A Basics56,57 B Monitoring & Infusion Practices

n Frozen plasma (FP) can be derived from How

two sources: n Frozen plasma must be transfused
u Whole blood donor plasma (290 mL) through a blood administration filter
u Apheresis donors (290 or 500 mL) (170-260 microns).
n FP is compatible ONLY with normal
• large apheresis units (500 mL) are equivalent
to 2 units of random donor plasma saline.

Dose58
n Small adult: 3 units (10-15 mL/kg).
n Large adult: 4 units (10-15 mL/kg).

Red Blood
Cell Basics
n
500 mL
Pediatric: 10 to 20 mL/kg.

When
290 mL n The recommended infusion time is
each
30-120 minutes per unit (maximum
time 4 hours).

Storage
n Frozen plasma is kept frozen for up
to one year.
2 Whole Blood 1 Apherisis u Once thawed, plasma can be stored

!
Donations Donation at 1-6 °C for 5 days A T T E N T I O N
n

Components
After issue, FP and FFPA should be The effective half-life of FP
administered within 4 hours. is measured in hours.
u The biological half-life of plasma Administer immediately
Notes:
n coagulation proteins is different before planned procedures.
‘Frozen plasma’ (FP) is frozen within
24 hours of collection and ‘Apheresis for each protein:59
• 3-6 hours for factor VII
Fresh Frozen Plasma’ (FFPA) is frozen
• 8-12 hours for factor VIII
within 8 hours.
• 2-3 days for factors II and XI
n The factor VIII is slightly lower in FP but
this is not clinically significant. All other Monitor patient
coagulation factor levels are the same n Check patient’s vital signs:
in FP and FFPA, and the 2 products can u prior to starting
be used interchangeably. u 15 minutes after starting
n FP and FFPA contain 400-900 mg fibrinogen u at end of transfusion
per 250 mL equivalent (4 units of FP contain u during any transfusion reactions
approximately 2.5 g of fibrinogen).
n Transfuse slowly (50 mL/hr) for the
first 15 minutes, where possible.
n

!
Monitor the patient closely for the A T T E N T I O N
first 15 minutes. Patients receiving plasma are
n If clinically indicated, the PT/INR at high risk for Transfusion-
and PTT should be checked after Associated Circulatory
infusion (10-60 minutes). Overload (TACO)!

34 35
 Transfusion Basics
C O M P O N E N T S : FP rl a
o tzeelne tPs l a s m a

C Indications for Frozen Plasma

To determine if FP is indicated for abnormal A T T E N T I O N Note: 61,62,63,64

coagulation test results, the cause of the FP is NOT indicated or n If available, prothrombin complex

!
elevation must be determined (i.e., liver disease required when INR <1.8 concentrates (PCCs) should be used
vs. warfarin effect vs. single factor deficiency). as coagulation factor for urgent reversal of warfarin therapy
See Section 4 of Bloody Easy Coagulation levels are adequate for or treatment of vitamin K deficiency
Simplified60 for details. The reasons for this hemostasis. in a bleeding patient OR a patient
are as follows: requiring an emergency invasive
n There are numerous replacement options procedure. Vitamin K (2-10 mg i.v.)
and the correct one must be selected for should also be given. See page 124
the patient (i.e., FP vs. Prothrombin Complex

!
in this guide.

Red Blood
Cell Basics
A T T E N T I O N
Concentrates (PCC) vs. single factor n For non-emergent reversal of warfarin
concentrate). IV Vitamin K works
or vitamin K deficiency, vitamin K
n Warfarin effect and vitamin K deficiency
faster than oral.
should be used rather than PCCs.
can often be managed with intravenous/ u For patients without bleeding and
oral vitamin K alone. INR >10 due to warfarin, 2 mg of
n Patients with liver disease have preserved A T T E N T I O N oral Vitamin K will bring INR within
thrombin generation despite elevated INR FP is NOT indicated or the therapeutic range over 24-48

!
levels and often do not need correction of effective for reversal of hours
the abnormality before procedures. heparin, low molecular u After intravenous administration,
n Patients with isolated high PTT (and weight heparin, Vitamin K effect can be detected
normal INR) are managed with strategies rivaroxaban, dabigatran, after 2 hours and the INR should
other than FP. apixiban or edoxaban.

Components
be normalized after 6-24 hours
n Patients on anticoagulants are never u SC and IM NOT recommended due

appropriately managed with FP.60 to variable absorption: intravenous

CHOOSE WISELY
formulation can be used orally when
1. Bleeding or prior to a significant operative required
Don’t transfuse plasma
procedure in patients with INR, PT or PTT in the following
1.8 times normal or greater due to multiple situations: Pediatrics 65
factor deficiency when no coagulation factor
u Bleeding and INR <1.8 Vitamin K dose:
concentrates or other alternative therapies
u n INR >5–9: 1 to 2 mg oral.
n INR ≥9: 5 mg oral.
Procedure and
are available.13
INR <1.8
u Repeating INR/PT/PTT after infusion
u
n Significant bleed in infants
INR elevated but
of FP may be beneficial to ensure
patient is not actively
that replacement is adequate9 and children: 5 mg IV OR
bleeding
30 mcg/kg IV.
u Warfarin reversal
u Heparin/LMWH
reversal
u Xa or IIa inhibitor
anticoagulant reversal
u High aPTT with
normal INR

36 37
 Transfusion Basics
C O M P O N E N T S : FP rl a
o tzeelne tPs l a s m a

C Indications for Frozen Plasma (cont’d)

2. Microvascular bleeding or massive A T T E N T I O N

transfusion AND patient’s clinical status Ratio based replacement
precludes waiting 30-45 minutes for (i.e., 2:1 RBC:FP) with

!
INR/PT/PTT results.13 FP not required when
patient is expected to
3. Thrombotic thrombocytopenic purpura. need less than 10 RBC
units over 24 hours or
time allows replacement
based on laboratory
testing.

Red Blood
Cell Basics
INR/PT/PTT INDICATION (PEDIATRIC AND ADULT PATIENTS)

1.8 or greater Active bleeding or prior to significant operative

procedure in patient with multiple coagulation factor
deficiency when no coagulation factor concentrates
or other alternative are available
Note: Patients with liver disease have preserved thrombin
generation despite elevated INR levels and often do not
need correction of the abnormality before procedures

Components
Results not Microvascular bleeding or massive transfusion AND
immediately patient’s clinical status precludes waiting 30-45 minutes
available for INR/PT/PTT results

Any Thrombotic thrombocytopenic purpura (TTP)

38 39
 Transfusion Basics
C O M P O N E N T S : Cryoprecipitate

A Basics38,66 B Indications

What n For bleeding with fibrinogen <1 g/L.38 CHOOSE WISELY

n It is acceptable to use non ABO compatible n For massive hemorrhage with Don't transfuse
cryoprecipitate, where required. fibrinogen <1.5-2.0 g/L.68 cryoprecipitate in the
n Cryoprecipitate contains factor VIII, n For acute phase of acute promyelocytic following situations:
factor XIII, fibrinogen, and von Willebrand leukemia with fibrinogen <1.5 g/L.69 u DIC with low
factor.
n
fibrinogen level
Intracranial hemorrhage secondary to
u Each unit of cryoprecipitate contains in the absence of
treatment with Tissue Plasminogen bleeding or a planned
a minimum of 150 mg of fibrinogen Activator with fibrinogen <2.0 g/L.
n 10 units of cryoprecipitate on average procedure (other than
n Treatment of bleeding in patients with the acute phase of
contains 4 grams of fibrinogen

Red Blood
Cell Basics
von Willebrand disease or Hemophilia A acute promyelocytic
only: leukemia)
u when factor concentrates are
How u Any congenital
n Cryoprecipitate must be given unavailable (remote geographic bleeding disorder
through a blood administration region); and
filter (170-260 microns). u DDAVP is unavailable or ineffective

n Cryoprecipitate is compatible ONLY

with normal saline.
C Alternatives to Cryoprecipitate
Dose
n Adults: 10 units. Pediatrics: 1 unit/10 kg
n Fibrinogen concentrates are licensed

Components
body weight to maximum of 10 units.
n
for congenital hypofibrinogenemia
Each dose will increase the fibrinogen
in Canada.
by 0.5 g/L in the bleeding patient.67
n
n
There is one fibrinogen concentrate
Recommended infusion time is
available in Canada: RiaSTAP™ (CSL
10-30 minutes per dose (maximum
Behring).
infusion time 4 hours).
n
n
The vials are 1 gram of lyophilized
Half-life of fibrinogen is about 7 days.
product that is reconstituted in
50 mL of sterile diluent.
n In hospitals where cryoprecipitate
can not be provided, it is reasonable
to utilize fibrinogen concentrates
(adult dose 4 grams equivalent to
10 units of cryoprecipitate).

40 41
 R I S K C H A R T S : R e f e r e n c e f o r P h y s i c i a n s*

Risk Charts
RISK OF EVENT EVENT Risk of death per 1 unit component
(likely an under-estimate)
1 in 13 Red cell sensitization, increasing risk of hemolytic n Note: Patient risk should be determined as
transfusion reaction and hemolytic disease of the a multiplication of the risk by the number
fetus and newborn70
of units transfused (or ‘donor exposures’).
1 in 20 Febrile non-hemolytic transfusion reaction per pool n Serious Hazards of Transfusion Program
of platelets71 (United Kingdom) 2014.
u 1 in 177,000 components issued possibly,
1 in 100 Transfusion-associated circulatory overload per
transfusion episode72 probably or definitely related to patient
death 73
n United States (Food and Drug
1 in 100 Minor allergic reactions (urticaria)

Transfusion Reactions
1 in 300 Febrile non-hemolytic transfusion reaction per unit of Administration) 2011.
RBC (1 ‘donor exposure’) u 1 in 360,000 components transfused

1 in 7,000 Delayed hemolytic transfusion reaction resulted in a death from transfusion74,75

n The Hemovigilance Network in France
1 in 10,000 Transfusion-related acute lung injury (TRALI) 2003.
u 1 in 208,000 components transfused
1 in 10,000 Symptomatic bacterial sepsis per pool of platelets
resulted in a death from transfusion 76
1 in 40,000 ABO-incompatible transfusion per RBC transfusion episode
1 in 40,000 Serious allergic reaction per unit of component
TRANSFUSION TRANSMITTED INJURIES SURVEILLANCE SYSTEM (TTISS), ONTARIO.
11 in
in 100,000
60,000 Post-transfusion
Death purpura
from bacterial sepsis per pool of platelets MAJOR ADVERSE EVENTS REPORTED 2008-2014 77

Blood Conservation
1 in 200,000 Death from bacterial sepsis per pool of platelets Acute Hemolytic
Reaction, 72, 6%
Anaphylactic Shock, 3, 0%
1 in 250,000 Symptomatic bacterial sepsis per unit of RBC TRALI*, 33, 3%

TAD†, 45, 4% Aseptic Meningitis, 16, 1%

1 in 500,000 Death from bacterial sepsis per unit of RBC Bacterial Infection, 29, 2%

<1 in 1,000,000 Transmission of West Nile Virus Other pain/unknown, 74, 6%

1 in 4,000,000 Transmission of Chagas disease per unit of component

TACO**, 326,
1 in 7,500,000 Transmission of hepatitis B virus per unit of component 27%

Delayed Hemolytic
Reaction, 222, 18%
1 in 7,600,000 Transmission of HTLV per unit of component
1 in 13,000,000 Transmission of hepatitis C virus per unit of component
1 in 21,000,000 Transmission of human immunodeficiency virus (HIV)
per unit of component
Hypotensive Reaction, 37, 3%

* All of these risk frequencies are likely to have quite wide confidence intervals.
IVIg Headache, 58, 5%
Severe
Allergic/Anaphylactic/ IVIg pain/reaction, 66, 5%
Anaphylactoid, 190, 15%
PTP††, 3, 0% Other Infection, 1, 0%
Possible TRALI, 51, 4%

* Transfusion-related acute lung injury (TRALI)

** Transfusion-Associated Circulatory Overload (TACO)
† Transfusion-associated dyspnea (TAD)
†† Post-transfusion purpura (PTP)
42 43
 R I S K C H A R T S : Reference for Patients

Risk Charts
RISK OF EVENT EVENT FREQUENCY OF NON-TRANSFUSION ASSOCIATED RISKS FOR
COMPARISON WITH RISKS OF COMPLICATIONS OF BLOOD TRANSFUSION
1 in 13 Red blood cell antibodies that can complicate future
pregnancies or transfusion HAZARD PROBABILITY
1 in 100 Hives (itchy skin rash) 1 in 10 78 Dying from lung cancer after smoking 1 pack a day for 30 years
1 in 100 Heart failure
1 in 60 79 Stroke within 30 days of cardiac surgery
1 in 300 Fever from red cell transfusion
1 in 100 80 Death associated with hip replacement surgery
1 in 7,000 Delayed hemolysis. Hemolysis is when your red blood
1 in 10,000 81 Annual risk of death in a motor vehicle crash

Transfusion Reactions
cells are destroyed
1 in 10,000 Lung injury 1 in 60,000 81 Annual risk of being murdered in Canada
1 in 10,000 Symptomatic bacterial sepsis, per pool of platelets. 1 in 200,000 82 Death from anesthesia in fit patients
Sepsis is when you get an infection in your bloodstream
or tissue 1 in 300,000 83 Death from oral contraceptives age <20 years
1 in 40,000 Wrong ABO (blood) group, per unit of red blood cells 1 in 1,000,000 81 Annual risk of death from accidental electrocution in Canada
1 in 40,000 Anaphylaxis, which is an extreme sensitivity to a drug 1 in 5,000,000 81 Annual risk of death from being struck by lightning in Canada
or substance that can result in death
1 in 200,000 Death from bacterial sepsis, per pool of platelets
1 in 250,000 Symptomatic bacterial sepsis, per unit of red blood cells

Blood Conservation
1 in 500,000 Death from bacterial sepsis, per unit of red blood cells
<1 in 1,000,000 Transmission of West Nile Virus
1 in 4,000,000 Transmission of Chagas Disease. Chagas Disease is a
parasite that can be transmitted through transfusion
1 in 7,500,000 Hepatitis B Virus (HBV) transmission per unit of
component
1 in 7,600,000 Human T-cell lymphotropic virus (HTLV) transmission,
per unit of component. HTLV is a virus that can be
transmitted by exposure to blood or sexual contact,
and can cause a form of cancer of the blood
1 in 13,000,000 Hepatitis C Virus (HCV) transmission, per unit of
component
1 in 21,000,000 Human Immunodeficiency Virus (HIV) transmission,
per unit of component

44 45
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
A Reporting B Reaction by Symptom

Attention: All transfusion reactions (mild A T T E N T I O N SYMPTOM CONSIDER PAGE

!
to life-threatening) and transfusion-related
Report all transfusion
errors must be reported to the hospital’s reactions to your hospital’s Fever Management Algorithm 48
transfusion service (blood bank). transfusion service. Possible Reactions:
u Bacterial sepsis or contamination 49
What
n The Transfusion Medicine Laboratory u Acute hemolytic transfusion reaction 51
u Febrile non-hemolytic transfusion reaction (FNHTR) 54
(TML) will investigate, assess and report

Transfusion Reactions
the event to Transfusion-transmitted
injuries surveillance system (TTISS) which Dyspnea Management Algorithm 55
will then report to Public Health Agency of Possible Reactions:
Canada (PHAC)*. In Québec, the hospital’s u Transfusion-related acute lung injury (TRALI) 56
transfusion service reports all transfusion u Transfusion-associated circulatory overload (TACO) 60
reactions to Québec Hemovigilance System,
which then reports to PHAC.
Urticaria & Management Algorithm 62
n Component reactions relating to the Other Allergic Possible Reactions:
quality of the product must also be Reactions/ u Anaphylaxis 63
reported to CBS/HQ. Anaphylaxis u Minor allergic reaction – Urticaria 65
n Plasma derivative reactions related to
quality must also be reported to the
particular manufacturer. Hypotension Management Algorithm 66

Blood Conservation
Possible Reactions:
How u Bradykinin mediated hypotension 67
n CBS/HQ and PHAC* reporting forms are
available from all hospital transfusion Hemolysis Possible Reactions:
services. After u Acute hemolytic transfusion reaction 51
u Contact your transfusion service for more Transfusion u Hemolysis not related to RBC alloantibodies 68
information u Delayed hemolytic transfusion reactions 68
u It is the transfusion service’s responsibility

to submit them to CBS/HQ and PHAC Cytopenias Possible Reactions:

After u Transfusion-associated graft versus
* www.phac-aspc.gc.ca (click on Infectious Diseases; Blood Safety) Transfusion host disease (TA-GvHD) 70
u Post-transfusion purpura (PTP) 72
u Transfusion-related alloimmune

thrombocytopenia 73
u Transfusion-related alloimmune neutropenia 73

Virus, Parasite u Viruses 74

and Prion u Parasites 76
Infections u Prions 76
u Other transfusion-transmissible agents 77

46 47
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
Fever BACTERIAL SEPSIS OR CONTAMINATION

MANAGEMENT ALGORITHM ETIOLOGY 84

n Blood components may be contaminated by:
Fever (and/or Shaking Chills/Rigors) 1. Skin commensals from the donor (each
>1 ºC increase in temperature venipuncture may result in a small skin
AND temperature >38 ºC during or up to 4 hours post infusion plug that may be retained in the
donation bag)
2. Unrecognized bacteremia in the donor
Immediate Management: 3. Contamination from the environment

Transfusion Reactions
1. Stop transfusion and maintain IV access or from handling of the product
2. Take patient’s vital signs n Organisms:
3. Re-check identification of patient & blood product u Serious morbidity and mortality occur most Direct Smear Atlas: A CD-ROM of
Gram-Stained Preparations of

FEVER
4. Physician assessment required frequently with Gram-negative bacteria,85 Clinical Specimens. Lippincott
5. Notify hospital transfusion service (blood bank), but are also reported with Gram-positive Williams & Wilkins.
even if transfusion restarted or completed skin bacteria
u A number of bacteria have been implicated,

including:84,86

Temperature ≥39 °C, hypotension/shock, tachycardia, shaking

Clerical error or serious symptoms?
Gram-negative Gram-positive
chills/rigors, anxiety, dyspnea, back/chest pain, hemoglobinuria/
oliguria, bleeding from IV sites, nausea/vomiting • Escherichia coli • Staphylococcus aureus
• Serratia marcescens • Staphylococcus

Blood Conservation
• Klebsiella pneumonia epidermidis
No Yes • Pseudomonas species • Bacillus cereus
• Yersinia enterocolitica

Administer acetaminophen 325-650 mg DO NOT RESTART TRANSFUSION

INCIDENCE 84,85,87,88,89,90

BACTERIAL SYMPTOMATIC FATAL

Continue transfusion cautiously SUSPECT CONTAMINATION SEPTIC REACTIONS BACTERIAL SEPSIS
under observation; likely a febrile 1. Hemolytic transfusion reaction;
non-hemolytic transfusion reaction Buffy coat 1 in 1,000 1 in 10,000 1 in 200,000
OR
platelet pool
2. Bacterial contamination
• Collect blood bank specimen to 1 unit of RBC 1 in 50,000 1 in 250,000 1 in 500,000
Stop the transfusion if patient re-check ABO-group
develops any of the above symptoms • Clamp tubing, send unit to hospital n Bacterial sepsis accounts for at least 10% of transfusion-associated
blood bank along with attached fatalities.74
IV solutions for bacterial cultures n Bacterial sepsis occurs most frequently with platelets due to their
and gram stain storage at 20-24 ºC for preservation of function.
• Send first post-transfusion urine n About two thirds are Gram-positive and one third Gram-negative.74
specimen
• Send blood cultures on patient
taken from a different IV site

48 49
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
CLINICAL PRESENTATION PREVENTION
n Clinical features of transfusion-associated n The skin is disinfected at the donation
sepsis may include: 88,91 site to reduce bacterial contamination
u Rigors, fever, tachycardia, hypotension,
by skin flora.
nausea and vomiting, dyspnea, disseminated n The first 40 mL of blood collected is
intravascular coagulation diverted and sequestered in a pouch
n It is usually possible to culture the offending to reduce risk of transmitting organisms
organism from both the patient and the from skin (can be used for infectious

Transfusion Reactions
transfused product. agent testing).
n
n There may be no immediate clinical signs Apheresis and buffy coat platelets are
of bacterial infection after transfusion of cultured by CBS/HQ prior to issue to A T T E N T I O N
hospitals.

!
bacterially-contaminated platelets, if the

FEVER
Keep RBCs in an approved
bacterial load is small. n RBCs are stored at 1-6 °C in a monitored fridge or cooler until
u Delayed presentation of symptoms up
blood bank refrigerator. immediately prior to
to 24 hours post-transfusion reported90 transfusion!

MANAGEMENT 89,91
n If transfusion-transmitted bacterial A T T E N T I O N ACUTE HEMOLYTIC TRANSFUSION

!
infection is suspected: REACTION
Stop transfusion immediately
u Stop the transfusion! if bacterial infection is

Blood Conservation
ETIOLOGY
u Notify the hospital transfusion service suspected.
n Acute hemolytic transfusion reactions
(blood bank)
may be associated with:
• Hospital transfusion service (blood bank)
u ABO-incompatibility
will notify the supplier so that:
u Other blood group incompatibilities
– other products from the same donor(s) can
be quarantined, cultured, and discarded AND • There are 29 blood group systems and
346 known blood group antigens that
– any recipients of other products can be
may cause incompatibility (in addition
identified and followed up
to ABO)92
u Return residual of blood product(s) and A T T E N T I O N u Rare cases when group O platelets with

!
tubing (clamped) for culture and gram
Arrange for Gram stain high titers of anti-A and/or anti-B are
stain to the hospital transfusion service
on unit(s) suspected of transfused to a non-group O recipient 93
u
n
Collect peripheral blood specimen for being contaminated. ABO-incompatibility:
blood culture from a different IV site
u Is due to a clerical error or other error in
u Provide aggressive supportive therapy as patient identification
appropriate, including broad-spectrum
u HALF of all errors are due to
antibiotics
A T T E N T I O N administering properly labelled blood

!
• DO NOT WAIT FOR RESULTS OF to the wrong patient 94
Start antibiotic therapy
BLOOD CULTURES PRIOR TO u Other errors are the result of improper
immediately, do not wait
STARTING ANTIBIOTIC THERAPY
for results of blood cultures. labelling of specimens or testing errors

50 51
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
n RBC alloantibodies (non-ABO): MANAGEMENT
u Result from patient immunization from n Stop the transfusion! A T T E N T I O N
a prior pregnancy or transfusion
u Causes of reactions include:

• Red cell alloantibodies in the patient’s

plasma below the level detected by
the antibody screen
n

n
Check if there is a clerical error. Check
identity of patient vs. patient identity
on blood product label.
Notify hospital transfusion service
(blood bank).
if acute hemolytic
reaction suspected. !
Stop transfusion immediately

• Clerical error during patient antibody n Send specimens to hospital transfusion

screening service to re-check ABO-group.
• Failure to detect RBC antibody due n Return residual of blood product(s) and

Transfusion Reactions
to limitations of the laboratory assay tubing (clamped) to the hospital transfusion
• Uncrossmatched blood transfused service.
n
to a patient who is alloimmunized
Send first post-transfusion urine specimen

FEVER
for urinalysis.
INCIDENCE
n Provide supportive care.
n 1 in 38,000 red cell transfusions are
u Maintain good urine output
ABO-incompatible due to transfusing
u Manage DIC and hemorrhage as
the wrong blood to a patient.94
n Less than 10% of ABO-incompatible clinically indicated
transfusions result in a fatal outcome.94
PREVENTION
n Over 50% of patients have no morbidity
n Pay meticulous attention to identifying
from an ABO-incompatible transfusion.
n
the patient and labelling the tubes at

Blood Conservation
Risk of death correlates with the amount
specimen collection (to ensure that patient
of incompatible blood transfused.95
is assigned to the correct blood group). A T T E N T I O N

CLINICAL PRESENTATION 96
n Most common clinical presentation is:
u Fever and chills

u Hemoglobinuria
n Pay meticulous attention to verifying
the patient’s identity, by checking
their wristband, before transfusing.
u Confirm the patient’s identity (for

patients that are conscious) verbally

Check the blood product

!
label with the patient’s arm
band identification, NOT
with a hospital card or chart.

u Less common: pain, hypotension, in case the patient’s armband is

nausea/vomiting, dyspnea, renal incorrect (armband errors do occur)
failure, DIC
n Fever may be the only presenting sign of
an acute hemolytic transfusion reaction.

52 53
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
FEBRILE NON-HEMOLYTIC TRANSFUSION Dyspnea
REACTION (FNHTR)
(Anaphylaxis is described under Allergic Reactions/Anaphylaxis)
ETIOLOGY
MANAGEMENT ALGORITHM
n Attributable to:97
u Soluble factors (e.g., cytokines) in the Dyspnea
plasma of the component transfused
u Recipient antibodies, reactive to antigens

expressed on cells in the component, Immediate Management:

usually white blood cells 1. Stop transfusion and maintain IV access with 0.9% saline

Transfusion Reactions
INCIDENCE 98
2. Take patient’s vital signs
3. Re-check identification of patient & blood product

FEVER/DYSPNEA
INCIDENCE
4. Physician assessment required
RBC 1 in 300 5. Notify hospital transfusion service (blood bank)
6. Return clamped blood unit with tubing attached
Platelet pool 1 in 20

CLINICAL PRESENTATION
Consider:
n Fever usually occurs during or up to 4 hours n TRANSFUSION-RELATED ACUTE LUNG INJURY (TRALI)
post transfusion.
n TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD (TACO)
u May be associated with chills, rigors, nausea,
n ANAPHYLAXIS
vomiting and hypotension
n If TRALI is suspected, notify hospital transfusion service

Blood Conservation
n Fever is not always present (i.e., chills, nausea, A T T E N T I O N

!
(blood bank) so that special donor and recipient testing
etc., alone). Fever is not a contraindication can be performed
to commencing a blood n Order STAT chest X-ray
MANAGEMENT transfusion!
n Oxygen, diuretics and supportive care as required, depending
n Acetaminophen
on type of reaction
n Meperidine (Demerol®) 25-50 mg IV may be A T T E N T I O N

!
effective for severe rigors if the patient has
Meperidine has numerous
no contraindications to meperidine.
serious drug interactions.
Consult pharmacy if the
PREVENTION
patient is on SSRIs, MAOIs,
n Pre-medication with acetaminophen and antibiotics, antifungals, or
diphenhydramine has not been shown to medications for seizures.
be effective in preventing FNHTR.99,100
n In patients with significant and recurrent
FNHTR, the following measures have been
used but efficacy is unproven:
u Acetaminophen, corticosteroids, fresh

components, plasma-depleted components,

washed red blood cells (washing platelets
results in 50% loss of platelets)
n Antihistamines are not effective.

54 55
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
TRANSFUSION-RELATED ACUTE
LUNG INJURY (TRALI) 101,102

DEFINITION OF ACUTE LUNG INJURY (ALI) ETIOLOGY

n n
RISK FACTORS FOR
Acute onset. Presently not fully defined. Two postulated
ACUTE LUNG INJURY
n Hypoxemia: mechanisms have been implicated:102,103
Predisposing factors
u PaO /FiO <300 mmHg; OR 1. Antibody-mediated: Passive transfer
2 2 for ALI include:
u Oxygen saturation is
of HLA or granulocyte antibodies from
n Direct Lung Injury donor to blood product recipient; or,
<90% on room air; OR
u Aspiration less commonly, HLA or granulocyte
u Other clinical evidence

Transfusion Reactions
u Pneumonia antibodies in the recipient (antibodies
n Bilateral lung infiltrates detected in donor or recipient in 80%
u Toxic inhalation
on the chest radiograph. of cases).104,105
u Lung contusion
n

DYSPNEA
No evidence of circulatory • Antibodies are most common in
u Near drowning
overload. multiparous female donors as a
n Indirect Lung Injury consequence of prior pregnancies
DEFINITION OF TRALI u Severe sepsis
2. Neutrophil priming hypothesis:
n In patients with no evidence of u Shock Biologic response modifiers such
ALI prior to transfusion, TRALI u Multiple trauma as biologically active lipids in the
is diagnosed if: transfused component may induce
u Burn injury
u New ALI is present TRALI in a susceptible patient.106
u Acute pancreatitis
u It occurs during or within 6 hours
u Cardiopulmonary bypass INCIDENCE
of completion of transfusion

Blood Conservation
u There are no other risk factors
u Drug overdose n True incidence of this syndrome is
for ALI (see orange box to the unknown; two separate hospital-based
right) reports estimate TRALI at 1 in 1,200 to
5,000 plasma-containing transfusions,
DEFINITION OF POSSIBLE TRALI respectively.104,107 (Both studies were
n
performed before TRALI reduction
In patients with no ALI prior to
measures.)
transfusion, possible TRALI is
diagnosed if: n The incidence of TRALI has decreased by
u New ALI is present
approximately half with implementation
of TRALI reduction measures with SHOT
u It occurs during or within 6 hours
and American Red Cross reporting large
of completion of transfusion reductions in cases (see Prevention).73,108
u There are one or more risk factors
n TRALI is known to be under-diagnosed
for ALI (see orange box to the right) and under-reported.

56 57
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
PRESENTATION MANAGEMENT
n Dyspnea, hypoxemia, fever and hypotension. n Supportive care, including mechanical
n Chest X-ray reveals interstitial and alveolar ventilation when clinically indicated.
infiltrates (pulmonary edema), without n Diuretics and steroids are not believed
elevated pulmonary pressures. to be useful in treating TRALI.111
n Usually occurs with transfusion of RBCs, n Accurate reporting to hospital transfusion
platelets and plasma, but rarely with other service is critical to identify implicated donors

Transfusion Reactions
blood products (including cryoprecipitate and prevent TRALI in other recipients.
and IVIG). n Patient and donor testing should be
n Almost always within the first 1-2 hours after arranged through the hospital transfusion

DYSPNEA
the start of transfusion but can be delayed service (testing performed through CBS/HQ).
for up to 6 hours.104
n
PREVENTION
Usually resolves in 24-72 hours.
n n Adherence to evidence-based transfusion
72% of reported cases required mechanical
ventilation and death occurs in 5-10% of guidelines.
patients experiencing a TRALI reaction.104 n Component strategies to reduce TRALI
n Milder forms of TRALI are thought to exist include:
and may present as transient hypoxia.109 u Plasma for transfusion predominantly from

n Acute transient leukopenia may be observed male donors

Blood Conservation
after a TRALI reaction.110 u Buffy coat platelet pools suspended in male

plasma
u Plateletpheresis collected from male donors
Chest X-ray of a patient before and during an episode
or never pregnant females
of transfusion-related acute lung injury (TRALI)
n Deferral of donors confirmed to be
implicated in an episode of TRALI, and
with either antibodies or implicated in
multiple episodes.

58 59
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
TRANSFUSION-ASSOCIATED
CIRCULATORY OVERLOAD (TACO) 112
ETIOLOGY PREVENTION A T T E N T I O N
n Circulatory overload results from: n Pre-transfusion assessment is important to The following are risk
1. Impaired cardiac function, AND/OR identify patients at risk and management factors for TACO:
2. Excessively rapid rate of transfusion should be adjusted accordingly. u Age over 70 years
n
u
Preventative measures include:

!
History of heart failure
INCIDENCE u Avoid transfusing more than one
u Left ventricular
n Current estimate of the frequency of TACO unit at a time dysfunction
u Transfuse over longer periods
range from 1 in 700 to 8% of transfusion u

Transfusion Reactions
History of myocardial
recipients.7 (maximum 4 hours) infarction
n u Pre-emptive diuretics
Patients over 70 years of age, infants, and u Renal dysfunction
patients with severe euvolemic anemia u Components can be split into smaller
u

DYSPNEA
Positive fluid balance
(hemoglobin <50 g/L), renal impairment, aliquots to further reduce the speed
fluid overload, and cardiac dysfunction of infusion without wasting product
A T T E N T I O N

!
are particularly susceptible. or increasing donor exposure A T T E N T I O N

!
TACO is the most common
cause of death from In patients at risk,
CLINICAL PRESENTATION
transfusion! avoid transfusing more
n Clinical presentation includes: dyspnea, than one unit at a time.
orthopnea, cyanosis, tachycardia, increased
venous pressure, and hypertension.
CHOOSE WISELY

Blood Conservation
MANAGEMENT Avoid unnecessary
n Interrupt the transfusion. A T T E N T I O N transfusion of blood
n
products and maximize
Administer oxygen and diuretics as needed. Interrupt transfusion.

!
n
the use of alternatives.
Chest x-ray. Administer oxygen and
n Consider restarting transfusion at a reduced diuretics if required.
infusion rate if clinical status allows and Consider restarting
product still viable. transfusion at reduced rate.

60 61
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
Urticaria & Other Allergic Reactions/Anaphylaxis ANAPHYLAXIS

MANAGEMENT ALGORITHM ETIOLOGY 113

n Vast majority of anaphylactic reactions are
Allergic Reaction unexplained.
n The following mechanisms have been implicated
A transfusion reaction that may be associated with urticaria, facial edema,
airway edema, lower respiratory tract symptoms, hypotension, or shock in anaphylaxis/anaphylactoid reactions:
u Anti-IgA in an IgA deficient recipient

u Antibodies to polymorphic forms of

ALLERGIC REACTIONS/ANAPHYLAXIS
Transfusion Reactions
α-1-antitrypsin, transferrin, C3, C4, etc.)
Immediate Management: serum proteins (IgG, albumin, haptoglobin,
1. Interrupt the transfusion & maintain IV access
2. Take the patient’s vital signs u Transfusing an allergen to a sensitized patient

3. Re-check identification of patient and blood product (e.g., penicillin, ASA, etc., consumed by
4. Physician assessment required donor)
5. Notify hospital transfusion service (blood bank) even if u Passive transfer of IgE (to drugs, food)

n
transfusion restarted or already completed
1 in 500 blood donors are IgA deficient
(IgA <0.05 mg/dL), and 1 in 1,500 blood
donors have anti-IgA, but most are NOT at
Clerical error, anaphylaxis or serious symptoms? risk of an anaphylactic transfusion reaction
1. Hypotension (reasons are not clear at this time).114
2. Dyspnea/cough u Anti-IgA as a cause of anaphylaxis from
3. Tachycardia
transfusion has recently been called into

Blood Conservation
4. Generalized flushing or anxiety
question due to the lack of evidence
5. Nausea/vomiting
6. Widespread rash > 2/3 body implicating IgA deficiency in this entity115
n Haptoglobin deficiency is not uncommon
in Asian patients (1 in 1,000) and has been
associated with anaphylactic reactions.116
No Yes
INCIDENCE
n Transfusion-associated anaphylactic shock
Consistent with minor allergic reaction DO NOT RESTART TRANSFUSION is rare.117
• Notify the patient’s physician STAT n Anaphylaxis accounts for approximately
• Notify the hospital transfusion 5% of transfusion associated fatalities.86
Give diphenhydramine 25-50 mg IV/po service (blood bank) immediately

Continue transfusion cautiously SUSPECT ANAPHYLACTOID

REACTION/ANAPHYLAXIS

Stop transfusion if patient develops

any of the above symptoms

62 63
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
MINOR ALLERGIC REACTION – URTICARIA

CLINICAL PRESENTATION 113 ETIOLOGY

n Reactions usually begin within 1 to n Unclear, but relates to factors in the
45 minutes after the start of the infusion. plasma portion of the component.
n Cutaneous reactions (urticaria) are present
in the majority of anaphylactic and INCIDENCE
anaphylactoid reactions. n Urticarial reactions are commonly
u When hypotension and hypoxia follow encountered: 0.42% of red blood cell,

ALLERGIC REACTIONS/ANAPHYLAXIS
Transfusion Reactions
transfusion, examine skin for urticaria 3.04% of platelet and 3.15% of plasma
(e.g., under drapes in operating room) transfusions.119
n Anaphylactic/anaphylactoid reactions are
CLINICAL PRESENTATION
associated with upper or lower airway
obstruction (symptoms may include n One urticarial lesion to widespread urticarial
hoarseness, stridor, wheezing, chest pain, lesions.
dyspnea, anxiety, feeling of impending n May be associated with pruritis, erythema,
doom), hypotension, gastrointestinal flushing, or mild upper respiratory symptoms
symptoms (nausea, vomiting), rarely death. (cough, wheezing), nausea, vomiting,
n Potentially life-threatening. abdominal cramps, or diarrhea.

TREATMENT MANAGEMENT A T T E N T I O N
n

!
n
A T T E N T I O N
Stop the transfusion! Do not restart. Interrupt the transfusion. Interrupt transfusion.
n

! n
Stop the transfusion

Blood Conservation
If severe urticarial reaction involving > 2/3 Give diphenhydramine 25-50 mg po or Give diphenhydramine.
if patient has
body surface area: Stop the transfusion IV depending on severity of the reaction. Restart transfusion slowly.
anaphylactic reaction.
and do not restart. Administer 25-50 mg n Restart the infusion slowly only if:
Do not restart.
diphenhydramine. 1. The urticarial rash involves < 2/3
n Anaphylaxis: Promptly administer of the body surface area; and,
epinephrine, corticosteroids, 2. There are no associated symptoms
diphenhydramine, vasopressors, suggesting a severe allergic reaction.
A T T E N T I O N
and supportive care as required.
n Provide ventilatory support as indicated
clinically.

PREVENTION OF RECURRENT ANAPHYLAXIS

n Pre-medication with intravenous steroids
Epinephrine should be

!
readily available whenever
transfusion is carried out.
PREVENTION
n If the urticarial reactions are recurrent, the
following precautionary measures may be
used although their efficacy is unknown:
u Pre-medication with diphenhydramine
and diphenhydramine. and/or corticosteroids
n If a patient is found to be IgA-deficient u Plasma depletion of RBCs or platelets
with anti-IgA, the following products
u Washed RBCs or platelets
are recommended:
u IgA-deficient blood products from IgA

deficient donors, available from CBS/HQ

u Washed RBCs (2L normal saline in

6 wash cycles) or platelets 113,118

64 65
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
Hypotension120 BRADYKININ MEDIATED HYPOTENSION

MANAGEMENT ALGORITHM ETIOLOGY

n Bradykinin is believed to play a major
Hypotension role in generating hypotension.
n Angiotensin-converting enzyme is the
>30 mmHg drop in systolic or diastolic blood pressure*
main enzyme responsible for degradation
of bradykinin.
u Some individuals have a genetic
Immediate Management: polymorphism resulting in a decrease

Transfusion Reactions
1. Stop the transfusion and maintain IV access in bradykinin degradation
2. Take patient's vital signs
3. Re-check identification of patient & blood product

HYPOTENSION
INCIDENCE
n
4. Consider differential diagnosis
Unknown.
5. Physician assessment required
CLINICAL PRESENTATION
n Majority of hypotensive reactions
Consider: occur with platelet transfusions.
n
1. Acute hemolytic transfusion reaction
Of reported cases, over half of the
2. Bacterial sepsis
patients were on ACE inhibitors.
3. Severe febrile non-hemolytic transfusion reaction
4. Bradykinin mediated hypotension n Other symptoms may be present,
5. Transfusion-related acute lung injury including dyspnea, urticaria, nausea,

Blood Conservation
6. Anaphylaxis and vomiting.
n Rarely associated with significant
morbidity or mortality.
No Yes
TREATMENT
unrelated to transfusion
n Detect early: Monitor the patient for A T T E N T I O N
the first 15 minutes and vital signs at Monitor patient for first

!
Possibly resume transfusion Do not restart transfusion. 15 minutes. 15 minutes and vital signs
after reassessing Refer to appropriate sections. n Stop the transfusion and do not re-start. at 15 minutes.
n Provide supportive care, including Stop transfusion if
* Definition refers to adult patients only intravenous fluids. hypotension develops.
n Consider acute hemolytic transfusion
reaction, sepsis, TRALI and allergic
Pediatrics reactions in the differential diagnosis.
Hypotension in children is defined as:
n Infants, children and adolescents (1 year to less than PREVENTION
18 years old): n In cases where ACE inhibitors were
u Greater than 25% drop in systolic BP from baseline.
implicated, consider (where possible)
n Neonates and small infants (less than 1 year old OR any an alternative anti-hypertensive prior
age and less than 12 kg body weight): to additional transfusions.
u Greater than 25% drop in baseline value using whichever

measurement is being recorded (e.g., mean BP).

66 67
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
Hemolysis After Transfusion INCIDENCE
n 8% of recipients will have newly formed
RBC alloantibodies detected in the first
HEMOLYSIS NOT RELATED 6 months.70
TO RBC ALLOANTIBODIES n 1 in 6715 units of RBCs transfused are
n Hemolysis may also occur in the following associated with a delayed hemolytic
settings and should be considered in the transfusion reaction.121
differential diagnosis of hemolysis after
transfusion: CLINICAL PRESENTATION

u Use of hypotonic IV solutions with n 3 days to 2 weeks after transfusion, the

Transfusion Reactions
RBC transfusions patient presents with hemolytic anemia
u Medical device-related (e.g., cell saver
(low hemoglobin, high bilirubin,
or blood warmer malfunction) reticulocytosis, spherocytosis, high LDH,

HEMOLYSIS
positive antibody screen, and a positive
u Overheating of RBCs due to improper
direct anti-globulin test).122
storage (e.g., RBCs placed on radiator)
u Freezing of RBCs (e.g., transport of blood COMPLICATIONS
directly on ice or storage in freezer) n Most are benign, but life-threatening
u Transfusion of RBCs under pressure
hemolysis with severe anemia and renal
through a small bore needle failure may occur.
u Transfusion of outdated or near outdated

RBCs TREATMENT
u Non-transfusion-related causes n Transfuse compatible blood (‘antigen

Blood Conservation
n Most are benign, but life-threatening negative’; i.e., if the offending antibody
hemolysis with severe anemia and is anti-Jka, then the transfusion service
renal failure may occur. will provide units that do not carry the
Jka antigen).

PREVENTION
DELAYED HEMOLYTIC TRANSFUSION n Avoid RBC transfusions.
REACTIONS n Use of antibody screening methods with
maximal sensitivity.
n
ETIOLOGY
Notify patient and provide an antibody
n Results from the formation of antibodies card for the patient to carry in their wallet.
in the recipient (to transfused red cell
alloantigens or from RBC antigen exposure
during a prior pregnancy) and below the
level of detection on the initial antibody
screen testing.
n Commonly implicated antigens are
(in order of frequency): E, Jka, c, Fya, K.121
n Delayed hemolysis may occur with transfusion-
transmitted malaria and babesiosis.

68 69
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
Cytopenias After Transfusion

TRANSFUSION-ASSOCIATED GRAFT PREVENTION

VERSUS HOST DISEASE (TA-GVHD) 123,124 n For patients at risk (see below), it is critical
to irradiate cellular blood components
ETIOLOGY
(RBC and platelets).
n TA-GvHD has been reported in n To avoid unacceptable high hemolysis
immunocompromised patients or in Recipient (>0.8%) and elevated potassium levels from
immunocompetent individuals transfused a irradiation, adherence to the Council of

Tolerance
fresh (<14 day old) haploidentical product.

Rejection
Europe’s guidelines is advised. Red cells

Transfusion Reactions
(The risk of an HLA-haploidentical donor in may be irradiated up to 28 days after
North America is estimated at 1 in 17,700 to collection and should be transfused as
39,000.)125,126

CYTOPENIAS
soon as possible, but no later than 14 days
u A donor who is homozygous for an HLA after irradiation, and no later than 28 days
type (haploidentical), whose blood product after collection.127,128
is transfused to a recipient who is
heterozygous for the same HLA type and a Donor PATIENTS REQUIRING IRRADIATED BLOOD 129
A T T E N T I O N

!
different HLA type places the recipient at risk
HLA-haploidentical u Patients with severe T-cell congenital
Some immunocompromised
• The donor’s lymphocytes mount a reaction patients must receive
against the non-matching HLA determinants immunodeficiency states irradiated blood. Refer
on the recipient’s cells u Intrauterine transfusions (IUT) to box to the left.
u Neonatal exchange transfusions for
INCIDENCE
infants with prior IUT

Blood Conservation
n Unknown; there were 13 cases reported u Neonatal top-up transfusion if there
in the UK SHOT program from 1996 to 2001; has been a previous IUT
since 2001 there has been one case in 2012
u Patients with Hodgkin’s lymphoma
attributed to failure to irradiate maternal
u Patients undergoing bone marrow or
blood for an intra-uterine fetal transfusion.73
stem cell transplants
CLINICAL PRESENTATION • It is reasonable to continue providing
n Fever, rash, liver dysfunction, and diarrhea irradiated products until
commencing 1-2 weeks post-transfusion immunosuppression discontinued
followed by pancytopenia later. u Recipients of directed transfusions from
n Overwhelming infections are the most family members
common cause of death. u Recipients of HLA-matched platelets
n Mortality is >90%.126 u Patients treated with purine analogs
n Diagnosis can be made by biopsy of skin, (e.g., fludarabine), purine antagonists
liver, or bone marrow. (e.g., bendamustine), alemtuzumab
n Confirmation requires documentation of the and anti-thymocyte globulin
presence of donor lymphocytes (e.g., HLA
typing, short tandem repeat analysis).
n Notify patient in need of irradiated blood
TREATMENT and provide a card for the patient to carry
in their wallet.
n Largely ineffective.
n Survival (which is rare) is attributed to
immunosuppressive therapy.

70 71
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
POST-TRANSFUSION PURPURA (PTP) 130
ETIOLOGY TREATMENT
n Transfusion of platelet antigen-positive n Test patient plasma for platelet-specific
RBCs, plasma, or platelets to a patient antibodies (performed at CBS/HQ).
who lacks the same platelet antigen. n Thrombocytopenia lasts approximately
u 75% of cases occur in an Human Platelet 2 weeks.
Antigen-1b (HPA-1b) homozygous patient n First-line therapy is IVIG at a dose of
who is transfused HPA-1a positive blood 1 g/kg daily for 2 days; the platelet count
products is expected to increase 4 days after the
u 3% of the North American population

Transfusion Reactions
start of therapy.
are HPA-1b homozygotes, but only
28% appear able to form anti-HPA-1a PREVENTION
n n

CYTOPENIAS
Autologous platelet destruction occurs Patients with PTP should receive antigen-
but the mechanism is unclear. negative RBC and platelet transfusions
(washed RBCs do not appear to be safe
INCIDENCE in this population).
n 1 in 100,000; post-transfusion purpura
occurrence among the inpatient U.S. elderly, WARNING
as recorded in large medicare databases n Affected patients (and their relatives)
during 2011 through 2012.131 are at risk of neonatal alloimmune
thrombocytopenia (NAIT). The family
CLINICAL PRESENTATION should be tested and counselled
n

Blood Conservation
There are 5 times as many female transfusion regarding both PTP and NAIT.
u NAIT occurs when a woman has

!
recipients with PTP as males, as a consequence A T T E N T I O N
of sensitization in a previous pregnancy. anti-platelet antibodies (usually
n anti-HPA-1a) and is carrying an antigen- Family members of patients
Occurs post-transfusion at a mean of nine with PTP are at risk of NAIT.
days (range 1 to 24). positive fetus; the infant is frequently
n
born with severe thrombocytopenia,
Platelet count is less than 10 x 109/L in 80%
and sometimes, intracranial hemorrhage
of cases.
n Mortality is 8% and the majority of deaths
are from intracranial hemorrhage. TRANSFUSION-RELATED ALLOIMMUNE
n Transfusions are frequently associated with THROMBOCYTOPENIA
n
fever, chills, rigors, and bronchospasm.
Uncommon cause of thrombocytopenia.
n
n
Differentiation from straightforward platelet
Due to platelet specific donor alloantibodies
alloimmunization is problematic.
to patient platelet antigens.132
u PTP should be considered when a platelet

refractory patient fails to respond to

HLA-matched platelets TRANSFUSION-RELATED ALLOIMMUNE
NEUTROPENIA133
n Rare cause of neutropenia.

72 73
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
Virus, Parasite and Prion Infections n An allogeneic stem cell transplant program
recently reported on a decade of patients
(Bacterial contamination is described under Fever) undergoing allogeneic transplant with
leukoreduction as the sole strategy without
VIRUSES a single patient developing transfusion
transmitted CMV.138
Risks n The current requirement for residual WBC
n Donating blood in the ‘window period’ – after leukoreduction is <5.0 x 106 WBC/unit.
the interval between the time of infectivity u For fiscal year 2014/15 the mean monthly

VIRUS, PARASITE & PRION INFECTIONS

and the appearance of detectable disease residual WBC far exceeded these

Transfusion Reactions
markers such as specific antibodies or viral requirements (data from CBS):
nucleic acid sequences.
• Pooled platelet – 0.006 x 106 WBC/unit
n Current ‘window period’ estimates are:134 (fail rate 0.00%)
u 10 days for HIV
• RBCs – 0.063 x 106 WBC/unit (fail rate
u 8 days for HCV 0.15%)
u 38 days for HBV n CMV serology must be drawn before
n
HIV Virus
Figures in chart below are risk per donor allogeneic transfusions commence, otherwise
exposure: (i.e., 1 unit of RBC).135,136 false positive results may be found due to
passive antibody detection.
West Nile Virus (WNV) <1 in 1,000,000

Hepatitis B virus (HBV) 1 in 7,500,000 West Nile Virus (WNV)

n No reported cases of transfusion transmitted

Blood Conservation
Human T-cell lymphotropic virus 1 in 7,600,000
WNV in Canada since nucleic acid testing of
donations began in 2003.139
Hepatitis C virus (HCV) 1 in 13,000,000
n Facts about transfusion-transmitted WNV:
HIV 1 in 21,000,000 u The virus can be transmitted through RBCs,

platelets, plasma, and cryoprecipitate, but

not through manufactured blood products
Cytomegalovirus (CMV): (e.g., albumin, IVIG, clotting factor
n Leukoreduced cellular components have a concentrates)
u The onset of symptoms post-transfusion
very low residual risk of transfusion
transmitted CMV. has ranged from 3 to 13 days (median
n It is unknown if CMV seronegative units have 7 days)
u Symptomatic recipients were primarily
any additional benefit to leukoreduction.
u The estimated residual risk of CMV from
immunocompromised patients; however,
leukoreduced red cell and platelet units post-partum and post-operative patients
is 1 in 13,575,000137 have been affected

74 75
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
PARASITES OTHER TRANSFUSION-TRANSMISSIBLE
AGENTS 140,144,145
Chagas Disease n Other rare infectious agents confirmed to
n Chagas Disease is caused by the protozoan be transmitted by blood components that
Trypanosoma cruzi found predominantly may cause symptomatic infection include:
in Central and South America. u Viral – Parvovirus B19, Hepatitis A and
n There have been 7 reported cases of E, Dengue, Chikungunya, Tick-borne
transfusion transmitted Chagas in US and encephalitis, Colorado Tick Fever,
Canada, mostly with platelet products.140 Human Herpes virus 8, SEN virus,

VIRUS, PARASITE & PRION INFECTIONS

n Since May 2010, at risk donors in Simian foamy virus and Zika virus

Transfusion Reactions
Canada are tested for Chagas Disease. u Protozoal – Malaria, Babesiosis,

n The current risk of transfusion- Leishmaniasis, Toxoplasmosis

transmission is estimated to be u Helminthic – Filariasis
1 in 4 million, based on U.S. data.141 u Spirochetal – Treponema pallidum

(Syphilis)
u Rickettsial – R. rickettsii (Rocky Mountain
PRIONS
Spotted Fever), R. burnetii (Q fever),
Variant Creutzfeldt-Jakob Disease (vCJD) Ehrlichia (Ehrlichiosis)
n 4 suspected cases of transfusion-associated n It is extremely important to report cases
transmission have been reported in of the above infections in transfusion
the U.K.142 recipients and recent blood donors.
n 1 suspected case of transmission from

Blood Conservation
U.K.-derived Factor VIII concentrate.143
n At present, high-risk blood donors
(resident in the U.K. or France for more
than 3 months, or Saudi Arabia for more
than 6 months between 1980-1996, or in Public Health Agency of Canada
Europe for more than 5 years between
1980 and 2007) are deferred in Canada.

76 77
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
Complications of Massive Transfusion
Definition n Mortality after massive transfusion is
n More than 10 units of RBCs, or, transfusing Pediatric inversely related to core temperature
more than one blood volume in a 24-hour definitions (data from 1987):152
150,151
period. u <34 ºC – 40%
n
n
Transfusion
Massive transfusion is an independent risk u <33 ºC – 69%
support to replace
factor for developing multi-organ failure.146 u <32 ºC – 100%
ongoing blood
loss of >10% n Every 1 °C drop in temperature increases
Complications147 A T T E N T I O N
n
TBV per min blood loss by 16% and the risk of

Transfusion Reactions
The complications described below are
n

!
Every 1 °C drop in

MASSIVE TRANSFUSION
dependent on the following factors: Transfusion transfusion by 22%.153
temperature increases
>100% TBV n Risk of clinically important hypothermia
u Number of units transfused blood loss by 16% and
in 24 hours is significantly increased by infusion of the risk of transfusion
u Rapidity of transfusion
n Transfusion >50% 5 or more units of blood.152 by 22%.153
u Patient factors
TBV in 3 hours n Consequences of hypothermia:
u Platelet dysfunction
1. Dilutional coagulopathy
n 50% of massively-transfused patients u Decreased coagulation factor activity

develop an INR >2.0 and about 33% u Reduced clearance of citrate

have thrombocytopenia with a platelet u Decreased cardiac output

count <50 x 109/L.148 u Hypotension
n Number of RBCs transfused does not A T T E N T I O N

!
u Arrhythmias (especially if cold blood
accurately predict the need for platelet

Blood Conservation
Use laboratory monitoring is transfused rapidly through a central
and FP transfusion; frequent laboratory where possible to guide the
line)
measurements are required to guide use of blood components.
transfusion decisions. 3. Hypocalcemia/Hypomagnesemia/
n In one large randomized controlled Citrate toxicity
trial, resuscitation of trauma patients n Citrate is the anticoagulant used in blood
with 1:1:1 was not found to be superior components.
n
to resuscitation with a ratio of 2:1:1
It is usually rapidly metabolized by the liver.
(RBC:FP:PLT).149
u A normothermic adult not in shock can
u Only patients with extremely rapid
tolerate upwards of 20 units per hour
hemorrhage were enrolled in this trial
A T T E N T I O N without calcium supplementation
and formula-driven resuscitation
n With massive transfusion, the capacity
should not be applied to less extreme RBCs currently contain
hemorrhage situations.149 20 mL of plasma or less. of the liver to degrade citrate may be

!
Trauma patients can safely be
overwhelmed.
2. Hypothermia transfused their native blood n Citrate binds ionic calcium and
n Rapid infusion of cold blood can result group if they have received magnesium, causing functional
in cardiac arrhythmias. 20 or less units of group O hypocalcemia, hypomagnesemia,
n Prevention is critical – if massive uncrossmatched RBCs and also metabolic alkalosis (from
transfusion is likely, use an approved (approximately 400 mL of bicarbonate, a metabolite of citrate).
group O plasma or less).
and properly maintained blood warmer.

78 79
 T R A N S F U S I O N R E A C T I O N S

Risk Charts
n Clinical symptoms include: hypotension, KEY COMPONENTS OF A HOSPITAL
narrow pulse pressure, elevated pulmonary MASSIVE HEMORRHAGE PROTOCOL
artery pressure, tetany, paresthesia and
arrhythmias. Every hospital must have a Massive
n If hypocalcemia develops OR patient Hemorrhage Protocol to ensure
develops signs or symptoms of standardized care is delivered.156
hypocalcemia then administer: n Prompt use of measures to prevent
u 1 gram (1 ampoule) of calcium chloride hypothermia, including use of a blood

Transfusion Reactions
IV at maximum rate of 100 mg/minute warmer for all IV fluids and blood

MASSIVE TRANSFUSION
components.
n Monitor core temperature and maintain
4. Metabolic acidosis
above 36 °C.
n
n Watch for dilutional coagulopathy
Rare; from acid pH of blood products.
n Usually, metabolic alkalosis occurs due with q1h blood work.
to bicarbonate production from citrate
u While patient is actively bleeding,
metabolism.
transfuse to keep:
n May be an indicator of lactic acidosis
• Platelet count >50 x 109/L
in patients with tissue hypoperfusion.
(with head injury >100 x 109/L)
5. Hyperkalemia154 • INR <1.8
n Release of potassium from stored RBCs • Fibrinogen >2.0 g/L
u

Blood Conservation
increases with storage time and after Institute ratio-based resuscitation
irradiation. if the required rate of transfusion
n Potassium concentration in a exceeds 4 units of RBC per hour
non-irradiated SAGM-RBC unit is u Administer tranexamic acid 1 gram IV

approximated by the number of days bolus and then 1 gram IV over 8 hours157
of storage (110 mL of supernatant/unit). n Watch for hypocalcemia, acidosis and
u For example, a 42 day old RBC hyperkalemia.
has a potassium concentration n Blood tubing must be changed every
of approximately 45 mmol/L155 2-4 units and within the number of
n Order bloodwork q1h (e.g., CBC, INR, hours specified by your hospital policy.
PTT, fibrinogen, calcium, arterial blood In massive transfusion this may be
gas, potassium). impractical so an add-on filter can be
used to minimize the frequency of
tubing changes. Rapid infusers with
large blood filters may allow for less
frequent tubing changes.

80 81
 Paitent Risk Chart
T R A N S F U S I O N R E A C T I O N S

Postpartum Hemorrhage (PPH)

n The above Massive Hemorrhage Protocol
also applies to the patient with a massive
postpartum hemorrhage.
n All postpartum females should be closely
monitored for early signs of hemorrhage
n Protocols for rapid administration of
uterotonics must be in place at all hospitals
with obstetrical patients.
n Use of intrauterine balloons should be a

Transfusion Reactions
key part of the early management while a
decision is being made regarding definitive
therapy (i.e., hysterectomy vs. uterine artery
embolization).
n RBC transfusion, when indicated clinically,
should NOT be delayed while waiting for
pre-transfusion testing and uncrossmatched
blood should be administered.
u uncrossmatched blood must be available

within 10 minutes of the onset of a

postpartum hemorrhage at all hospitals
with obstetrics
n

Blood Conservation
Maintain fibrinogen level above 2.0 g/L with
early and aggressive use of cryoprecipitate.158

82 83
 B L O O D C O N S E R V A T I O N

Risk Charts
Blood Conservation in the Perioperative Setting

Patient Blood Management Programs are A T T E N T I O N Blood Conservation Strategies

the vehicle for delivery of blood conservation Through Patient Blood The following blood conservation strategies
measures, and may be defined as integration are available, listed according to when they

!
Management Programs,
of multi-modal, multi-disciplinary measures appropriate blood should be implemented perioperatively:
to reduce the risk of unnecessary transfusion conservation measures
and optimize patient outcomes.159,160 must be offered to all TIME UNTIL SURGERY BLOOD CONSERVATION STRATEGIES AVAILABLE PAGE
n There are currently several perioperative patients with a >10%
chance of blood exposure.
blood conservation strategies available >35 days u Investigate and treat anemia –

Transfusion Reactions
to patients. u Delay surgery until anemia corrected –
n Patients that are at high risk of perioperative u Iron 88
transfusions (>10% chance of allogeneic RBC
transfusion) must be identified as early as
10-35 days u Delay surgery until anemia corrected –
possible, preferably at least 28 days before
surgery, and must be offered appropriate u Erythropoietin 92
blood conservation strategies. u Iron 88
u As transfusion risk varies from institution

to institution and surgeon to surgeon <10 days u Delay surgery (if possible) until anemia –
for the same procedure, each institution before surgery corrected
must determine its own requirements
for transfusion
Intraoperative u Attention to surgical hemostasis 86

Blood Conservation
u Antifibrinolytics
Likelihood of Transfusion 94
n The risk of transfusion is increased by the u DDAVP 96
following factors: lower hemoglobin, older age, u Intraoperative cell salvage 90
lower weight, female gender, type of surgery, u Regional anesthesia
urgency of surgery, and renal dysfunction. 96
u Topical hemostatic agents
n Shown here is the probability of transfusion 96
(e.g., fibrin sealants)
for patients undergoing cardiac surgery
u Adherence to strict transfusion guidelines
based on pre-operative hemoglobin.161 16

84 85
 Chart
B L O O D C O N S E R V A T I O N

Charts
Risk Risk
GOOD SURGICAL TECHNIQUE
n Using good surgical technique(s) is critically n Dabigatran (Pradaxa®):

Paitent
important in reducing a patient’s exposure u Consider stopping therapy 2-4 days before

to allogeneic blood. major surgery in patients with normal renal

function
Recommended surgical practices u In patients with renal dysfunction (creatinine
n The following good clinical practices are
clearance <50 mL/min) consider stopping
highly recommended:
4-5 days before major surgery
u Assess and treat nutritional status
n Rivaroxaban (Xarelto®) and Apixiban (Eliquis®):
preoperatively
u Consider stopping therapy 2-3 days before major
u Maintain normothermia intraoperatively

Transfusion Reactions
surgery in patients with normal renal function
u Careful ligation of blood vessels
u In patients with renal dysfunction (creatinine
u Avoid tissue trauma
clearance <50 mL/min) consider stopping
u Optimal use of electrocautery
3-4 days before major surgery
u Meticulous attention to surgical hemostasis
n NSAIDs:
u Utilize avascular tissue planes
u Consider stopping therapy 4-7 days
u Appropriate use of topical hemostatic agents
before major surgery
u Celecoxib does not inhibit platelet
Consider stopping anti-platelet and
anticoagulants before major surgery aggregation at usual doses
n Acetylsalicylic acid (Aspirin®), clopidogrel Minimize blood sampling and loss165
(Plavix®) and prasugrel (Effient®):162,163 n Restrict diagnostic phlebotomy.
u In most clinical situations, withholding
n
A T T E N T I O N
Use small volume tubes and testing methods.

Blood Conservation
ASA before non-cardiac surgery is not
n
Do not stop antiplatelet
associated with an increase in adverse Conduct bedside microanalysis.
n
agents without
cardiac events164 consultation with the Remove arterial and venous catheters when
u Primary prevention: 48 hours minimum,
no longer necessary.

!
patient’s cardiologist
7 days preferable or neurologist, if:
Preoperative patients on Warfarin:166
u Secondary prevention (after remote MI,
n
• recent thrombosis
(MI, stroke)
If low risk of thromboembolic events
stroke, peripheral artery disease)
(e.g., primary prophylaxis of atrial fibrillation):
• low risk of bleeding procedure • recent percutaneous
u Stop warfarin 4-5 days preoperatively;
(e.g., cataract surgery, plastic surgery): coronary intervention
(PCI) repeat INR 1 day preoperatively
no need to stop antiplatelet agents
u If INR >1.5 then give 2 mg oral vitamin K
• high risk of bleeding procedure • coronary stent in
u Then repeat INR preoperatively
(e.g., neurosurgical procedure): last 12 months
n If high risk of thromboembolic events
48 hours minimum, 7 days preferable
u
(e.g., recent deep vein thrombosis):
Secondary prevention (high risk for arterial
u Consider switch to unfractionated or
thrombosis – recent percutaneous coronary
intervention, MI, stroke OR coronary stent low molecular weight heparin 4 days
<12 months) preoperatively; consult with hematology
on timing and preferred regimen or consult
• consult patient’s cardiologist or neurologist
recommendations at http://thrombosiscanada.ca/
for expert advice
• only stop antiplatelet agents if risk of Emergency reversal of anticoagulants
bleeding exceeds risk of cardiovascular n See page 126.
complications

86 87
 Chart
B L O O D C O N S E R V A T I O N

Charts
Risk Risk
IRON
n All patients undergoing procedures with Common Adverse Events*

Paitent
significant blood loss should be evaluated n GI upset (diarrhea, nausea, constipation) was twice as
for iron deficiency and where present frequent with oral iron as with placebo.178
corrected preoperatively.160 n Dark stools.
n There are several randomized trials of n Patient compliance with oral treatment is about 50%.179
iron therapy administered perioperatively,
* See product monograph for details
finding that:
u Preoperative iron may be helpful

for patients with low preoperative INTRAVENOUS IRON

Transfusion Reactions
hemoglobin levels, but not confirmed n There is currently insufficient evidence to support the
beneficial in all studies167,168,169,170 A T T E N T I O N routine use of intravenous iron in elective surgery
u Randomized trials failed to confirm a patients.180

!
Routine post-operative iron
benefit of post-operative iron therapy
therapy in preoperatively n Patients with iron deficiency anemia (whose surgery
in patients that were not anemic should not be delayed to allow for oral iron therapy to
non-anemic patients
preoperatively171,172,173,174,175,176 is NOT useful. correct the anemia) may be treated with intravenous
iron, in addition to oral iron.181 IV iron tends to restore
Dosage iron stores and hemoglobin levels more rapidly than
n 60 mg of elemental iron/day is sufficient A T T E N T I O N oral iron.179,182,183
for the majority of patients. (Higher doses

!
Ensure anemic patient Dosage
do not appear to improve the response,
is prescribed 60 mg u Check your hospital’s formulary to determine the
higher doses decreases compliance, and
of elemental iron recommended type of parenteral iron
higher doses causes decreased absorption (e.g., ferrous sulphate

Blood Conservation
by increasing the hormone hepcidin.)177 Adverse reaction
300 mg once daily).
u 24/100,000 risk of anaphylactic reaction to iron dextran184

u 16/100,000 risk of anaphylactic reaction to iron sucrose

COMMONLY USED IRON REPLACEMENT THERAPIES DOSE MG ELEMENTAL MG Venofer®184
u Give sufficient iron to correct the anemia (e.g., 300–
Ferrous gluconate 300 35
1,000 mg of elemental iron, Venofer® 300 mg in 250 mL
Ferrous sulfate 300 60 of normal saline over 2 hours for 1-3 infusions.)
Ferrous fumarate (Palafer®) 300 100
Polysaccharide-iron complex (FeraMax®) 150 150 Pediatric
FeraMAX (15 mg elemental iron per ¼
Polysaccharide-iron complex (Triferex®) 150 150
teaspoon)185
Proferrin 398 11 n May be dissolved in water or mixed into soft
foods or powdered cereals:
u Age based dosing:
Pediatric Dose 6 mg elemental iron/kg body weight
• Less than 2 months: ¼ teaspoon daily
PREPARATION (ORAL LIQUID) CONCENTRATION ELEMENTAL IRON • More than 2 months to 13 yrs: ¼ to ½
Ferrous fumarate (Palafer®) 60 mg/mL 20 mg/mL teaspoon daily
• More than 13 yrs to 18 yrs: ¼ to ¾ teaspoon
Ferrous sulphate (Fer-in-sol) 75 mg/mL 15 mg/mL
daily

88 89
 Chart
B L O O D C O N S E R V A T I O N

Charts
Risk Risk
INTRAOPERATIVE CELL SALVAGE Complications

!
n Complications include: A T T E N T I O N

Paitent
Principles u Air embolism – ensure air is removed Air embolism is a risk of
n A patient’s own blood shed at the time prior to re-infusion intraoperative cell salvage.
of an operation is collected and processed u Thrombocytopenia and dilutional
in such a way that it can be re-infused into coagulopathy
the patient (auto-transfusion).
u Bacterial contamination (rare)
n Up to 80% of red cells can be recovered.186
u Tumour dissemination in cancer surgery

Indication u Hemolysis – ensure correct wash fluids

n Meta-analysis of 75 studies:187 are used

Transfusion Reactions
u Cell salvage in orthopedic surgery (all types u A formal maintenance program is required

of salvage devices, washed and unwashed) for equipment

• Relative risk of transfusion 0.46 (95% CI
0.37-0.57)
Contraindications
n Malignant cells in operative field (risk may
u Cell salvage in cardiac surgery (unwashed only)
be mitigated by leukoreduction filter).
• Relative risk of transfusion 0.77 (95% CI n Bacterially-contaminated operative fluid,
0.69-0.86) ascitic fluid, or amniotic fluid in operative field.
u No increase in adverse events in the
n Use of hypotonic solutions in the operative
treatment group field.
n Meta-analysis of 31 randomized controlled n Use of topical thrombogenic agents in the
trials, including 2282 patients, in the setting operative field.
of cardiac surgery found that cell salvage

Blood Conservation
decreased the risk of allogeneic blood
exposure (OR 0.63, 95% CI 0.43-0.94,
P=0.02).188
n Consider in the setting of: trauma, hepatic
resection, major orthopedic and spine
surgery, or ruptured aneurysm with
appropriate quality assurance.
n May be an acceptable alternative for
some Jehovah’s Witnesses (see Appendix B,
page 145).

90 91
 Chart
B L O O D C O N S E R V A T I O N

Charts
Risk Risk
ERYTHROPOIETIN IN ELECTIVE SURGERY

Paitent
Principles Contraindications (in elective surgery patients)
n Erythropoietin stimulates erythropoesis n Uncontrolled hypertension.
and is produced in response to hypoxia n Hypersensitivity to mammalian-derived cell
by the renal cortex. Regulation is by products, albumin, or other components of
classical negative feedback inhibition. the product.
n Erythropoietin is administered n Contraindicated in patients scheduled for
prior to elective surgery to increase elective surgery with severe arterioscerotic
hemoglobin and thereby reduce disease.
the rate of allogeneic transfusion.189

Transfusion Reactions
For more details, refer to product monograph.
u Expected rise in hemoglobin is

10-20 g/L
Adverse Effects
n Safety of short-term use before surgery
Eligibility and Dosage has not been thoroughly studied.
n
n
Patients with a hemoglobin <130 g/L
A recent study found an increased risk
and a probability of requiring a blood
of thrombosis in patients undergoing
transfusion of 10% or greater.189,190,191
elective spine surgery.197
n Preferred dose: 600 U/kg sc qwk for up
For more details, refer to product monograph.
to 4 doses commencing 28 days before
surgery.192,193,194
u e.g., 30,000 or 40,000 U sc qwk x

Blood Conservation
4 weeks, start 28 days pre-op
n Alternative dose: 300 U/kg sc qd x
15 days commencing 10 days
preoperative.195
u e.g., 20,000 U sc qd x 15 days, start

day 10 pre-op
n Supplemental iron advised.196

92 93
 Chart
B L O O D C O N S E R V A T I O N

Charts
Risk Risk
ANTIFIBRINOLYTICS

Paitent
General Principles198,199 The CRASH-2 study, which included over A T T E N T I O N
n Inhibitors of plasminogen activation are 20,000 patients (most from developing Tranexamic acid saves

!
administered to prevent/treat increased countries), provides strong evidence of 1 in 68 traumatically
fibrinolysis during surgery, particularly benefit for tranexamic acid in patients injured patients from death
cardiac surgery. with traumatic hemorrhage (dose used: if administered within
1 g loading over 10 minutes, then 3 hours of injury!
infusion of 1 g over 8 hours).157
Indications n The use of topical tranexamic acid
1. Antifibrinolytics in Cardiac Surgery198,200 in knee and hip joint replacement is

Transfusion Reactions
n Prophylactic administration is preferred equally effective as intravenous use.204
rather than at time of marked
hemorrhage. Adverse Effects
n
n Tranexamic acid reduces bleeding and
Tranexamic acid: GI upset, seizures.
u Data from meta-analyses do not suggest
transfusion rates.
an increased risk of thrombosis199
2. Tranexamic Acid in Non-Cardiac
Surgery157,201,202,203 Contraindications205
n n Tranexamic acid – patients at elevated risk
Used in orthopedic surgery, trauma, and
hepatic surgery. of thrombosis, pregnancy; dose adjustment
n Evidence suggests a high degree of safety:
required in renal failure.
u A major meta-analysis included 252 RCTs
Refer to product monograph for more details.

Blood Conservation
including over 25,000 participants
u In the tranexamic acid trials, there was

a significant reduction in allogeneic

transfusion (RR 0.61, 95% CI 0.53-0.70)

94 95
 Chart
B L O O D C O N S E R V A T I O N

Charts
Risk Risk
DDAVP OTHER BLOOD CONSERVATION STRATEGIES
n There is no convincing evidence that UNDER CLINICAL INVESTIGATION

Paitent
A T T E N T I O N
DDAVP minimizes perioperative allogeneic The following blood conservation strategies
DDAVP is not indicated as

!
RBC transfusion in patients who do not a routine practice in the
are obsolete, under investigation or highly
have congenital bleeding disorders and prevention or treatment limited in application:
its routine use is not recommended.206,207,208 of bleeding after n Pre-operative autologous blood donation.
n DDAVP is of no benefit in the management cardiac surgery. n Hemoglobin-based oxygen carriers.214
of bleeding post cardiac surgery.209
n Recombinant factor VIIa.215
n Hypervolemic hemodilution.
n
REGIONAL ANESTHESIA

Transfusion Reactions
Acute normovolemic hemodilution.
n One systematic review of literature found
that the use of neuroaxial blockage with
epidural or spinal anesthesia reduced the
risk of:210
u transfusion

• risk of transfusion was reduced by 50%

u venous thromboembolism
u pneumonia and respiratory depression

TOPICAL AGENTS 200,211

n Fibrin sealants:

Blood Conservation
u Mixture of fibrinogen, thrombin, calcium

chloride and anti-fibrinolytic agent

u Meta-analysis of 18 trials indicates

effectiveness in reducing peri-operative

allogeneic blood transfusion (RR 0.63
95% CI 0.45-0.88)212
n Topical thrombin:
u Bovine thrombin products are not

recommended for clinical use200

u Recombinant human thrombin available

(e.g., Recothrom®)213
u No data on effectiveness in reducing

peri-operative allogeneic blood transfusion

96 97
 and Medical Patients
Erythropoietin
E R Y T H R O P O I E T I N and Medical Patients

General Principles216,217 CHRONIC RENAL FAILURE (CRF)219,220

n Erythropoietin (EPO) is synthesized Rationale
n Patients with end-stage renal disease are unable
by DNA technology:
u Currently available formulations
to produce erythropoietin; it is administered as a
in Canada do not contain albumin replacement therapy.
n Requires readily available iron for n Erythropoietin decreases the likelihood of
full efficacy. transfusion (RR 0.32, 95% CI 0.12-0.83).221
n Takes time to increase hemoglobin
(weeks). Eligibility
n EPO response to anemia may be n Patients with clinically and biochemically
blunted in the presence of malignancy, established CRF with a hemoglobin <90-110 g/L

Blood Products
chemotherapy and chronic inflammatory should be considered.222,223

Fractionated
diseases. n Usually erythropoietin is considered when the
creatinine clearance is <60 mL/min/1.73 m2.224
Indications n Other causes of anemia must be excluded or
n Chronic renal failure.
successfully treated:
n Anemia associated with malignancy. u Initial laboratory work up should include a CBC,

reticulocyte count, serum ferritin, and transferrin

Contraindications218
saturation
1) Uncontrolled hypertension.
2) Known sensitivity to mammalian cell derived Target therapeutic outcome
products. n To maintain the hemoglobin in the range of
3) Hypersensitivity to the active substance or

Sickle Cell Disease

100 to120 g/L.218,225,226
to any of the excipients.
4) Patients scheduled for elective surgery, who Iron 227
are not participating in an autologous blood n Assess iron status every 3 months.
pre-deposit program and who have severe n Sufficient iron should be administered to maintain
coronary, peripheral arterial, carotid or the serum ferritin >100 ug/L (not on hemodialysis)
cerebral vascular disease, including patients or >200 ug/L (on hemodialysis) AND iron
with recent myocardial infarction saturation >20%.
n Intravenous iron is frequently utilized for patients
or cerebral vascular accident.
5) Surgery patients who for any reason cannot who fail oral iron.
n Intravenous or oral iron is acceptable for CRF
receive adequate antithrombotic prophylaxis
or treatment.
patients not on hemodialysis.
n Patients should be monitored to prevent iron
6) Patients who develop Pure Red Cell Aplasia
(PRCA) following treatment with any
overload.
erythropoietin should not receive EPREX
n Stop iron if ferritin >500 ug/L.
or any other erythropoietin (see PRCA
paragraph in Precautions in monograph). Refer to intravenous iron product monographs for more details.
Refer to product monograph for more details.
Dosage
n Correction Phase:
u Initial dose of Epoietin Alfa (EPREX) -50 IU/kg of

body weight three times a week intravenously or

subcutaneously or darbopoietin (Aranesp™)
0.45 ug/kg sc per week
98 99
 and Medical Patients
Erythropoietin
E R Y T H R O P O I E T I N and Medical Patients

u If the hemoglobin does not increase by ANEMIA ASSOCIATED WITH MALIGNANCY

10 g/L after one month of treatment, the Eligibility 228,229
n Patients with chemotherapy-induced
dosage may be raised to 75 IU/kg three
times per week (EPREX) or by 25%
anemia; AND
(Aranesp™)
n Hemoglobin <100 g/L and/or requiring
u If further increments are needed they should
red cell transfusions.
be at 25 IU/kg, three times per week, at
u Other contributing causes of anemia
monthly intervals, to achieve a hemoglobin
NOT to exceed 120 g/L must be excluded or successfully treated
u u Carefully weigh the risks of thrombo-
The maximum dosage should not exceed
200 IU/kg three times per week embolism in patients prescribed
erythropoietin
n

Blood Products
Maintenance Phase:

Fractionated
• The relative risk of thromboembolic
u The intravenous/subcutaneous dose adjusted
complications is increased (RR 1.52,
individually to maintain a hemoglobin not
95% CI 1.34-1.74).230
to exceed 120 g/L
u Erythropoietin should not be used in
u The maintenance dose should be
treatment of anemia associated with
individualized for each patient with
malignancy in patients not receiving
chronic renal failure
chemotherapy
u The recommended weekly dose is
• A meta-analysis of 91 studies including
between 75 and 300 IU/kg
20,102 patients suggested erythropoietin
u In patients who are converting from
therapy increases the risk of death compared
the subcutaneous to intravenous route, to placebo (Hazards Ratio 1.05, 95% CI
the same dose should be used

Sickle Cell Disease

1.00-1.11)230
u Follow hemoglobin closely (e.g., weekly)
• Red blood cell transfusion should be
so that appropriate changes in the dose considered the preferred strategy in patients
can be made to keep the hemoglobin in undergoing potentially curative treatment
the target range
n Dose Adjustment: Target outcome
u If the hemoglobin is increasing and n To maintain the lowest hemoglobin level
approaching 120 g/L, the dose should sufficient to avoid RBC transfusions.
be reduced by approximately 25% n Erythropoietin increases the hemoglobin
u If the hemoglobin continues to increase, level and decreases the likelihood of
withhold treatment until the hemoglobin transfusion (RR 0.65, 95% CI 0.62-0.68).230
begins to decrease, then resume therapy
at a dose approximately 25% below the Dosage
previous dose n Iron status should be assessed and iron
u If the hemoglobin increases by more than deficiency treated.
10 g/L in any two week period, decrease n Concurrent iron therapy recommended
the dose by by approximately 25% unless there are concerns of iron overload.
u Dose reduction may be achieved either n Start erythropoietin with a dose of either:
by reducing the amount per dose or the u EPREX 150 U/kg sc 3 times/week or 40,000
number of doses per week, or both U sc weekly; or Darbepoetin 2.25 ug/kg sc
n Where inadequate responses occur, weekly or 500 ug every 3 weeks sc
re-examine for other causes of anemia. n Adjust dose per product monograph to avoid
major fluctuations in hemoglobin level.
100 101
 and Medical Patients
Erythropoietin
FRACTIONATED BLOOD PRODUCTS : A l b u m i n

A Basics B Administration & Infusion Practices

n Albumin is a plasma protein synthesized Dosage

by the liver and catabolized by the n Caution: Administering 25% albumin A T T E N T I O N
endothelium (daily turnover 9-12 g;
average total body albumin of a 70 kg
patient is 280 g; ~60% interstitial).231 n
in error, instead of 5%, could result
in severe circulatory overload.
For dosage, see specific indications !
Administering 25% albumin
instead of 5% in error could
result in circulatory overload!
n

!
Manufactured by cold ethanol A T T E N T I O N
listed below.
fractionation from a pool of Albumin is a blood product. n Intravascular volume response:
approximately 10,000 blood donors. Consent required.
n Viral inactivation steps include cold ethanol 500 mL 5% albumin 100 mL 25% albumin*

Blood Products
fractionation, and heat inactivation.

Fractionated
n In 2014-2015, 8 million grams of albumin
were used in Canada, at a cost of about = 25 grams of albumin = 25 grams of albumin
$15 million dollars.

500 mL increase 450 mL increase in

in intravascular intravascular volume
volume (350 mL from
interstitial pool)
*25% albumin usually restricted to use in patients with
liver failure

Sickle Cell Disease

Administration 232,233
n No crossmatch is required.
n Use regular IV tubing.
n Fluid compatibility: all IV solutions.
n Record lot number and volume of
albumin administered in patient chart.

Adverse reactions /Risks

n Anaphylaxis – rare.
n Circulatory overload.
n Hypotension – rare case reports of transient
hypotension in patients on angiotensin-
converting enzyme inhibitors.234
n There are no reports of HIV, HCV, or other
viruses transmitted through albumin.

102 103
 and Medical Patients
Erythropoietin
FRACTIONATED BLOOD PRODUCTS : A l b u m i n

C Indications

ALBUMIN MAY BENEFIT THE FOLLOWING DOSAGE

GROUPS OF PATIENTS: n 25% albumin – 1.5 g per kg within 6 hours
of diagnosis and 1.0 g per kg on day 3.
1. Paracentesis u For example: for a 70 kg patient =
n Albumin has been shown to reduce 4 x 100 mL of 25% albumin on day 1
morbidity and mortality in the management and then 3 x 100 mL of 25% albumin
of tense ascites by paracentesis.235 on day 3
n For paracentesis of <5 litres – albumin is
unnecessary.236
n For large volume paracentesis, albumin

Blood Products
3. Hepatorenal syndrome A T T E N T I O N

Fractionated
should be considered as the replacement n Preliminary data suggests that albumin

!
fluid of choice. Use of Intravenous
in conjunction with terlipressin243,244,245 or
albumin alone is
midodrine/octreotide246 may be effective
VOLUME OF ASCITES # VIALS OF 100 ML 25% ALBUMIN* ineffective for
in salvaging some patients with type 1 hepatorenal syndrome.
<5 L 0 hepatorenal syndrome who are candidates
for liver transplantation. There is evidence
5-8 L 2
that the combination of terlipressin and
8-12 L 3 albumin has a greater beneficial effect
on renal failure than the combination
12-15 L 4-5
of either midodrine or octreotide with
* 8 grams albumin per L of fluid removed for paracentesis >5 L.237 albumin.247

Sickle Cell Disease

u This therapy has not been shown to
n There is preliminary evidence that
midodrine238 and terlipressin239 may change mortality rates in hepato-renal
be alternative therapies to intravenous syndrome
u Albumin alone, without terlipressin
albumin in this setting, but have not been
or other agent is ineffective

!
shown to be superior to albumin.240 A T T E N T I O N
n Malignant ascites – there is no evidence DOSAGE
There is no evidence to
to support the use of albumin in patients n 100-200 mL of 25% albumin daily with
support the use of albumin
with malignant ascites post-paracentesis.241 in patients with malignant above agents, up to a maximum of
ascites post-paracentesis. 14 days.244,245,246

2. Spontaneous bacterial peritonitis

n One RCT (n=126) found that patients 4. Plasma exchange
resuscitated with antibiotics alone compared n Currently, the majority of patients
to antibiotics plus albumin had a higher undergoing therapeutic plasma exchange
mortality (OR 4.5, 95% CI 1.0 to 20.9).242 are replaced with albumin ± crystalloid or
u This study has been criticized for lack starch, with the exception of patients with
of a formalized resuscitation protocol thrombotic thrombocytopenic purpura (TTP)
in the control arm who are replaced with cryosupernatant or
frozen plasma.

104 105
 and Medical Patients
Erythropoietin
FRACTIONATED BLOOD PRODUCTS : A l b u m i n

THE CURRENT MEDICAL LITERATURE CANNOT n Current expert opinion recommends PARKLAND FORMULA
CONFIRM ANY BENEFIT OF INTRAVENOUS ALBUMIN resuscitation with lactated Ringer’s solution Parkland Formula =
IN THE FOLLOWING SUBGROUPS OF PATIENTS: 248 according to the Parkland formula, with 4 mL/kg/% burn over the
addition of colloids if the fluid volume first 24 hours, with half of
exceeds 4 mL/kg/% burn (known as ‘fluid the total fluid given in the
1. Resuscitation creep’) and urine output is less than
n
first 8 hours to target urine
Current evidence: albumin is not superior 0.5 mL/kg/hour, with hemostatic instability output to 0.5-1.0 mL/kg/hr.
to crystalloid for resuscitation in intensive after the first 8-24 hours.254,255
n
care.
Intravenous albumin should only be
n
A T T E N T I O N
A large randomized controlled trial 249

!
commenced after transfer to a specialized
showed no overall advantage of albumin Intravenous albumin should
burn centre.
over crystalloid for resuscitation in intensive only be commenced after

Blood Products
care patients. 4. Hypotension during dialysis transfer to a specialized

Fractionated
n n
burn centre.
A large randomized trial in critically ill There are currently no data to support
patients with hypovolemic shock (half the use of albumin in the treatment of
with septic shock) found no difference hypotension during dialysis.
in 28 day mortality when albumin was u Small comparison trials of normal saline,
compared to crystalloid.250 albumin (20%), and starch did not suggest
a superiority of albumin over the other
2. Hypoalbuminemia agents 256
n Current evidence: albumin is NOT superior to u A small RCT concluded that 5% albumin
crystalloid for treatment of hypoalbuminemia.
was no more effective than normal saline
n One meta-analysis showed a significant for the treatment of hypotension during
increase in mortality and another showed dialysis257

Sickle Cell Disease

a non-significant increase in mortality
compared to crystalloid: 5. Cardiac surgery258
n There is no evidence to support the use
ODDS RATIO (OR)* OR RANGE % INCREASE IN MORTALITY
of albumin, as compared to starch or
Cochrane Injuries crystalloid, for either:
1.69 1.07-2.67 69% (7 to 167%)
Group 248 i. Priming fluid for cardiopulmonary bypass
Wilkes et al 251 1.59 0.91-2.78 59% (-9 to 178%) ii. Post-cardiopulmonary bypass
n There is no evidence from randomized
3. Severe burns clinical trials in cardiac surgery patients that
n
fluid replacement with albumin is associated
4 small randomized controlled trials with
with a better pulmonary, cardiac, or renal
important methodological limitations in
outcome.
patients with thermal injuries failed to
show that 5% albumin was superior to 6. Acute Lung Injury
n
crystalloids.248,252
Two small, industry funded randomized
n There is currently a wide variation in fluid control trials (n=40 259, n=37 260) in
resuscitation practice in burn patients.253 hemodynamically stable patients found
the combination of furosemide and
intravenous albumin to result in weight loss
of 10 kg over 5 days, without improvement
in the rate of extubation success or mortality.

106 107
 and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

A Basics Cost IN 2015-2016

n IVIG costs $54 per gram, depending Canada (minus Quebec) used
on US$ exchange rate. 4,780 kg of IVIG at a cost of
IVIG is the fraction extracted from donated
u A single course of treatment for a $235 million dollars.263
plasma that contains the immunoglobulins,
with >90% as IgG. 70 kg patient with the commonly
prescribed dose of 1 g/kg each day
for 2 days, costs $7,500

Availability & Consumption

n Approximately 20% of the IVIG used
in Canada is derived from Canadian
plasma.263
n

Blood Products
The rest is derived from paid U.S. donors.

Fractionated
Products Available 261 n Canada has the highest per capita
n

!
Products are supplied by CBS or HQ. A T T E N T I O N consumption of IVIG in the world.264
n Informed consent is required as for IVIG is a blood product. IVIG USED IN CANADA, 2010-2011 TO 2014-2015
any blood component or product. Consent required. IN THOUSANDS OF KILOGRAMS
Refer to product’s package insert for further details.
7,000

IVIG PRODUCTS LICENSED IN CANADA* 6,000 IN ONTARIO

PRODUCT IGIVNEX GAMUNEX PRIVIGEN GAMMAGARD GAMMAGARD HIZENTRA OCTAGAM In Ontario, requests for IVIG
5,000
LIQUID S/D for infusion are required to
4,000 be made on a MOHLTC –

Sickle Cell Disease

Manufacturer Grifols Grifols CSL Baxalta Baxalta CSL Octapharma
Behring Behring mandated request form.
3,000
Plasma Canada United United United United United United The IVIG request form
Source States States States States States States can be found at
2,000
IgG (g/L) 98 ± 20 100 ± 10 100 100 >90 200 100 www.transfusionontario.org.
IgA (mg/L) 46 mcg/mL 46 mcg/mL 2.5-12 ≤140 ≤2.2 ≤50 <400 1,000
(average) (average) mcg/mL mcg/mL mcg/mL mcg/mL mcg/mL
(5.6 mcg/mL (in 5% 0
average)262 solution) 2010-2011 2011-2012 2012-2013 2013-2014 2014-2015
Sugar Not Not Contains Not 20 mg/mL Contains Maltose
content specified specified no carbo- specified (2%) no carbo- 90 mg/mL
hydrate glucose hydrate Manufacturing
stabilizers (in 5% stabilizers n IVIG is manufactured from pooled plasma
solution)
no sucrose obtained from several thousand donors per pool.
Osmolality 258 258 320 240-300 Not 380 310-380 n The constituent plasma units are tested for
(mOsmol/kg) indicated
in product
human immunodeficiency virus (1 and 2),
monograph hepatitis B, hepatitis C, human T-cell
Form Liquid Liquid Liquid Liquid Lyophilized Liquid Liquid lymphotropic virus (I and II), and parvovirus B19.
Route of IV IV/SC IV IV IV SC IV n The process includes rigorous viral inactivation
adminis-
tration
steps (e.g., caprylate, low pH, chromatography,
solvent detergent treatment).
* Consult appropriate package insert for more details, or for information on other products that n There is no evidence of transmission of prion
may be supplied if licensed products are not available.
disease (e.g., variant CJD) through IVIG.
n Steps in manufacturing are believed to reduce
the risk of transmission of prion disease.265

108 109
 and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

B Administration & Infusion Recommendations IVIG INFUSION RATES*

Administration PRODUCT INITIAL RATE MAXIMUM RATE COMMENT

n For detailed recommendations for IGIVnex 0.6-1.2 mL/kg/hour Increase gradually to Time to infuse 70 g
infusion of IVIG, refer to “Intravenous (0.01-0.02 mL/kg/min) a maximum rate of is approximately
Immune Globulin Toolkit for Ontario”.266 for 30 minutes 8.4 mL/kg/hour if 1 3/4 hours
n
initial dose is tolerated
Administered as 5% or 10% solution
usually dispensed by the Transfusion GAMUNEX™ 0.6-1.2 mL/kg/hour Increase gradually to Time to infuse 70 g
Medicine Laboratory or Pharmacy. (0.01-0.02 mL/kg/min) a maximum rate of is approximately
n Safe for use in pregnancy. for 30 minutes 8.4 mL/kg/hour if 1 3/4 hours
initial dose is tolerated
Refer to package insert for further details.
GAMMAGARD® A 5% solution should be Increase gradually Use of ante-

Blood Products
General Principles SD™ used for initial infusion to a maximum rate cubital vein is

Fractionated
n Refer to Institution specific policies at 0.5 mL/kg/hour. If of 8.0 mL/kg/hour recommended,
n Use Adjusted Body Weight Dosing DOSE CALCULATOR well tolerated, use 10% if initial dose is especially for
solution subsequently tolerated 10% solution
Calculator267, check every 6 months http://ivig.transfusionontario.
at the same rate. Use
or if significant weight change. org/dose/
filter supplied with
n Round dose to nearest vial size. product

Pre-infusion GAMMAGARD® 0.5 mL/kg/hour Increase gradually to

n Verify documentation of order, clinical Liquid (0.01 mL/Kg/min) a maximum rate of
for 30 minutes 8.0 mL/kg/hour if
indication and consent.
n
initial dose is tolerated
Identify patients at risk for complications,
especially TACO (see page 60) and Privigen 0.3 mL/kg/hour Increase gradually Product

Sickle Cell Disease

thromboembolic events. (0.005 mL/kg/min) to maximum rate monograph
n
of 7.2 mL/kg/hour recommends
Check vital signs. (4-8 mg/kg/min) slower rate to be
used for patients
Infusion
n
receiving >1 g/kg
Slow initial rate for first 30 minutes. (4 mg/kg/min)
n Check vital signs.
n
OCTAGAM Initial 0.6 mL/kg/hr Escalate to a
Increase rate and monitor vital signs as per for 30 minutes maximum of
institutional policy. 4.2 mL/kg/hr if initial
n Monitor for signs of adverse reactions and dose tolerated
report according to institutional policy.
* Refer to package insert for further information.
Post-infusion
n Complete documentation including dose,
brand and lot number.
n Report and return to the TML or Pharmacy
any unused or defective vials, and any vials
associated with an adverse event.

110 111
 and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

B Administration & Infusion Recommendations (cont’d) C Indications

Adverse reactions
n In the event of an adverse reaction, stop Immunology C H O O S E W I S E L Y
the transfusion and assess the patient; if n There is good evidence to support Immunoglobulin
the adverse reaction is minor, the transfusion the use of IVIG in congenital and (gammaglobulin)
may be continued at a reduced infusion rate. acquired immunoglobulin deficiency, replacement does not
n Report all adverse reactions to your hospital with the following conditions: improve outcomes unless
transfusion service. u Significant quantitative or functional there is impairment of
antibody deficiency that has been antigen-specific IgG
established (see the “Choose Wisely” antibody responses to
vaccine immunizations
ADVERSE REACTIONS TO IVIG 266,268,269,270,271 statement)
or natural infections.
u Clinical evidence consistent with

Blood Products
Fractionated
Isolated decreases in
REACTION SEVERITY FREQUENCY** COMMENT/TREATMENT defective humoral immunity immunoglobulins (isotypes
Anxiety, chills/fever, Mild- Common Slow or pause IVIG treatment. (e.g., recurrent infection) or subclasses), alone, do
rash, flushing, moderate Symptomatic treatment. Recurrent u The full text describing a scoring not indicate a need for
headache, chest, back reactions – pre-medicate and/or system to aid clinical decision immunoglobulin
or abdominal pain, change to another manufacturer’s
making regarding immunoglobulin replacement therapy.
nausea/vomiting, IVIG product
tachycardia, hypo- therapy is available at Exceptions include
or hypertension ncbi.nlm.nih.gov/pubmed/23518142277 genetically defined/
u Treatable conditions to which
suspected disorders.
Aseptic meningitis Moderate 7 in 10,000272 Stop infusion. Administer analgesics.
Measurement of IgG
Usually resolves spontaneously in antibody deficiency may be
24-48 hours subclasses is not routinely
secondary must be excluded useful in determining the
Anaphylaxis Severe Rare Stop infusion. May require n Subcutaneous immunoglobulin

Sickle Cell Disease

need for immunoglobulin
epinephrine promptly. Consider also available for home-based therapy. Selective IgA
testing for IgA and anti-IgA
(see page 63) immunoglobulin replacement deficiency is not an
therapy. Consult a transfusion indication for
Acute renal failure Severe Rare Usually with sucrose-containing
medicine specialist or immunologist administration of
(120 cases product (none currently licensed
reported to in Canada). Predisposing factors: for additional information. immunoglobulin.
FDA in 13 years) age >65, diabetes mellitus,
pre-existing renal insufficiency
IVIG IN IMMUNOGLOBULIN DEFICIENCY 278,279
Hemolysis Mild- 10%273,274 More common in non-group O
Severe patients
DIAGNOSIS EFFICACY/COMMENT DOSE
Thrombo-embolic Severe 0.5-1%275 Causative relationship not clearly
events established. Possibly related to Primary Immune IVIG is Adult: 0.4-0.6 g/kg/
increases in viscosity Deficiency280 recommended every 4 weeks
in hypogamma-
Infectious disease Severe No reported Modern viral reduction measures
transmission case since HCV are robust. Prion (vCJD) transmission Secondary Immune globulinemia (total Pediatric: 0.3-0.6 g/kg/
in 1995.276 No remains an entirely theoretical risk Deficiency (SID) IgG or IgG subclasses every 4 weeks
known case of reduced) with
transmission of recurrent bacterial Monitor IgG trough level
HIV or HBV infections to maintain low range

** Reactions are more likely with faster rates of infusion. Hematopoietic Stem Cell IVIG is 0.4-0.6 g/kg/every 4 weeks;
Transplant in primary recommended requirements may increase
immunodeficiencies281 in PID patients and should be based on
undergoing stem clinical outcome
cell transplant

112 113
 and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

IVIG IN SOLID ORGAN TRANSPLANTATION281 Hematology

IVIG IN HEMATOLOGICAL DISORDERS AND
DIAGNOSIS EFFICACY/COMMENT DOSE
BONE MARROW/STEM CELL TRANSPLANTATION278,280,286,287
Kidney transplant from IVIG is recommended 2 g/kg/month for 4 months
living donor to whom to decrease donor- DIAGNOSIS EFFICACY/COMMENT DOSE
the patient is sensitized281 specific sensitization
Immune Thrombocytopenic (ITP) Benefit established 1 g/kg for 1 day.
Pre-Transplant (heart)281 For desensitization Suggested dose is up refractory to standard treatment, Repeat if platelet
in selected heart to 1 g/kg/month until platelet count <20 x 109/L count not >30 x 109/L
transplant recipients transplant
ITP with persistent or life-threatening Benefit established 1 g/kg for 1-2 days
who are highly
bleeding and platelet count <50 x 109/L
sensitized, medically
urgent and unlikely Thrombocytopenia associated with Benefit established 1 g/kg for 2 days

Blood Products
Fractionated
to receive a transplant HIV unresponsive to antiviral therapy,
otherwise – this should platelet count <20 x 109/L or <50 x 109/L
be preceded by with bleeding
discussion at the ITP in pregnancy Appropriate initial 1 g/kg; longest
transplant program u platelet count <10 x 109/L treatment inter-treatment
level u platelet count 10-30 x 109/L in interval consistent
Peri-Transplant Solid-organ transplant Suggested dose 1 g/kg, can 2nd or 3rd trimester with maintaining
(heart, lung, kidney, recipient with donor- give as divided doses if in u platelet count <30 x 109/L and adequate platelet
pancreas)282,283,284,285 specific antibodies association with a course bleeding at any stage in pregnancy count
identified at time of of plasmapheresis
Post-transfusion purpura Recommended as 1-2 g/kg over
transplant surgery
first-line treatment 2-5 days
(heart, lung, kidney,

Sickle Cell Disease

pancreas) on virtual Fetal/neonatal allo-immune Considered standard Maternal:
crossmatch – first-line thrombocytopenia (F/NAIT) first-line antenatal 1 g/kg weekly
agent (treatment of mother or fetus) treatment.
Considered Infant: Give IVIG if
Post- Acute antibody- 1 g/kg/dose, can give Pediatrics adjunctive therapy platelet transfusion
Transplant281,282,283,284,285 mediated rejection as divided doses if in n Transfuse platelets for newborn with not immediately
in a solid-organ association with a course to maintain platelets F/NAIT. Appropriate available or there
transplant recipient – of plasmapheresis over 30 x 109/L. consultation is no response to
first-line agent n Transfuse platelets in the advisable with platelet transfusion
Chronic antibody- 1 g/kg/month setting of life-threatening high-risk pregnancy or prolonged
mediated rejection hemorrhage (intracranial thrombocytopenia
and neonatal unit
or GI bleeding) to maintain
in a solid-organ (>7 days). Dose
platelets over 100 x 109/L.
transplant recipient 1.0 g/kg and reassess

114 115
 and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

Hematology
IVIG IN HEMATOLOGICAL DISORDERS AND BONE MARROW/
STEM CELL TRANSPLANTATION280 (cont’d)

DIAGNOSIS EFFICACY/COMMENT DOSE DIAGNOSIS EFFICACY/COMMENT DOSE

Pure red cell aplasia (PRCA) Considered first line Up to 2 g/kg Rare cases of auto-immune Anecdotal evidence 1 g/kg for 2 days.
(viral or immunologic)279,286 therapy for PRCA divided over hemolytic anemia or only; consider use only Determine in
associated with 2-5 consecutive neutropenia, auto-antibodies after failure of other consultation
parvovirus B19 occurring days to factor VIII or von Willebrand treatments or in
in an immuno- factor278,279,286 urgent situations
compromised patient.
Allogeneic bone marrow/ IVIG is not recommended Not indicated.
Reasonable option for

Blood Products
stem cell transplant278,289 for routine use after HSCT. Determine in

Fractionated
immunologic PRCA
IVIG may be considered in consultation
in patients who have
exceptional cases: 1) No recommended
failed other therapies
1) Active CMV-induced dose or duration
Hemolytic transfusion IVIG may be considered Up to 2 g/kg pneumonitis following listed; use in
reaction (HTR)286 as an option among divided over transplantation conjunction
supportive therapies 2-5 days, short with appropriate
2) High-risk allogeneic
for urgent situations term up to antiviral
stem cell transplantation
in this disorder 3 months medication
(e.g., if hypogamma-
globulinemia) for 2) 0.4 g/kg weekly,
prevention of GVHD starting one
Hemolytic disease of the fetus Not recommended for 0.5 g/kg day before

Sickle Cell Disease

and newborn (HDFN)278,286 use in management of transplantation
HDFN without established (Unlikely to be and continuing
hyperbilirubinemia. of benefit with to day 100
Recommended if total ABO-hemolytic post-transplant
serum bilirubin is rising disease of the
despite intensive newborn as IVIG
phototherapy or if level contains anti-A
is within 34-51 umol/L and anti-B)
of the exchange level288

Virus associated hemophagocytic Not recommended for Determine in

syndrome (VAHS)286 routine use. Option in consultation
severe life threatening
VAHS

116 117
 and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

Neurology

IVIG IN NEUROLOGICAL DISORDERS*278,290

DIAGNOSIS EFFICACY/COMMENT DOSE DIAGNOSIS EFFICACY/COMMENT DOSE

Guillain-Barre Benefit established. Total dose of 2 g/kg Acute disseminated IVIG is an option for Adults: Total dose of
Syndrome (including Recommended as treatment divided over 2-5 days encephalomyelitis monophasic ADEM when 2 g/kg divided over
Miller-Fisher option within 2 weeks of symptom (adults) or 2 days (ADEM)279,290 first-line therapy with high-dose 2-5 days
syndrome and onset for patients with severe (children). Evaluate corticosteroids fails or when
other variants)291 and/or progressing symptoms. response at 4 weeks there are contraindications to Pediatric: Total dose
May be considered as a treatment steroid use, and for treatment of 2 g/kg divided over
option for relapsed patients of relapsing ADEM to eliminate 2 days

Blood Products
Fractionated
who initially responded to IVIG steroid dependency or for those
patients who fail to respond,
Chronic inflammatory Benefit established; option for Total dose of 2 g/kg or have contraindications to
demyelinating short-term management of divided over 2-5 days: steroids
polyradiculopathy292,293 new-onset CIDP or relapse. 1g/kg q3weeks as
Option for long-term therapy maintenance and then Lambert-Eaton IVIG is an option for treatment Initial treatment: Total
in combination with other adjust accordingly Myasthenic Syndrome of LEMS. Objective evidence of dose of 2 g/kg divided
immunosuppressive therapy (LEMS)279,290 clinical improvement is needed over 2-5 days
for sustained use of IVIG.
Multifocal motor Benefit established. Total dose of 2 g/kg Maintenance therapy:
neuropathy294 Recommended as first-line divided over 2-5 days; A systematic approach
therapy. Diagnosis should be maintenance therapy should be taken to
made by neuromuscular specialist should be individualized determine the minimum

Sickle Cell Disease

and tailored to the effective dose, and
lowest dose that continued use of IVIG
maintains clinical should be based on
efficacy (usually objective measures of its
1 g/kg or less) sustained effectiveness.
Myasthenia First line treatment for moderate 2 g/kg over 2-5 The maximum dose of
gravis295,296,297,298 to severe exacerbations or crises. days: maintenance IVIG per treatment
Should not be used as maintenance therapy should be course should be 2 g/kg
therapy. Appropriate consultation individualized
Pediatric Autoimmune IVIG is an option for treatment Total dose of 2 g/kg
advisable
Neuropsychiatric of patients with PANDAS. divided over 2 days is
Disorders Associated Diagnosis of PANDAS requires recommended as a
* Other conditions where IVIG is not of proven value include paraprotein polyneuropathy, With Streptococcal expert consultation reasonable option
neurological vasculitides, paraneoplastic neurological syndromes and autism. Infections
(PANDAS)279,290
Rasmussen’s IVIG is an option as a short- Adults: Total dose
encephalitis279,290 term, temporizing measure of 2 g/kg divided
for patients with Rasmussen’s over 2-5 days
encephalitis. Not recommended
for long-term therapy Pediatric: Total dose
of 2 g/kg divided
over 2 days

118 119
 and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

Neurology Rheumatology

IVIG IN NEUROLOGICAL DISORDERS* (cont’d) IVIG IN RHEUMATOLOGY

DIAGNOSIS EFFICACY/COMMENT DOSE DIAGNOSIS EFFICACY/COMMENT DOSE

Stiff Person’s IVIG is an option for treatment Initial treatment: Idiopathic Inflammatory IVIG is indicated in patients Total dose of
syndrome279,290 of Stiff Person syndrome if Adults: Total dose of myopathy with Idiopathic Inflammatory 2 g/kg divided over
GABAergic medications fail 2 g/kg divided over Includes: Dermatomyositis myopathy as adjunctive therapy 2-5 days (adults)
or for patients who have 2-5 days and Polymyositis to corticosteroids and/or a steroid or 2 days (children);
contraindications to GABAergic references300 sparing agent in patients with maintenance
medications Pediatric: Total dose Idiopathic Inflammatory therapy should
of 2 g/kg divided myopathy who have failed be individualized

Blood Products
first-line therapy or as clinically

Fractionated
over 2 days
indicated in the management
of severe disease
Maintenance therapy:
A systematic approach Systemic lupus Current evidence does
should be taken to erythematosus**301,302,303 not support use
determine the Kawasaki Benefit established 2 g/kg x 1 day
minimum effective disease 304,305,306,307,308
dose, and continued
use of IVIG should be ** For immune thrombocytopenia associated with systemic lupus erythematosus, see Hematology.
based on objective
measures of its Dermatology
sustained effectiveness.

Sickle Cell Disease

Maximum dose of IVIG
per treatment course IVIG IN DERMATOLOGY
should be 2 g/kg
DIAGNOSIS EFFICACY/COMMENT DOSE
NMDA IVIG is an option for treatment Initial treatment: Total
Encephalitis299 of patients with NMDA. dose of 2 g/kg divided Toxic epidermal IVIG is an option when other 1 g/kg daily for
Diagnosis of NMDA requires over 2-5 days in adults necrolysis 309 treatments are contraindicated, 3 days
expert consultation. IVIG is and children or when the condition is life-
used in conjunction with threatening
immunosuppressive medications Maintenance therapy: Pemphigus vulgaris Consider IVIG when there is no Total dose of 2 g/kg
and/or plasmapheresis May be considered and variants 278,279 response or a contraindication divided over 2-5
depending on to corticosteroids and days. Maintenance
response to treatment immunosuppressive agents treatment should
Opsoclonus-myoclonus Possible treatment option. Total dose of 2 g/kg be individualized
syndrome Objective evidence of clinical given over 2-5 days Epidermolysis bullosa Anecdotal evidence 310 supports Total dose of 2 g/kg
improvement required for (adults) or 2 days acquisita use of IVIG as adjunctive or divided over 2-5
sustained use (children) second-line treatment if days. Maintenance
conventional treatment is treatment should
* Other conditions where IVIG is not of proven value include paraprotein polyneuropathy, ineffective be individualized
neurological vasculitides, paraneoplastic neurological syndromes and autism.
Bullous pemphigoid Anecdotal evidence 311 supports Total dose of 2 g/kg
use of IVIG as second-line divided over 2-5
treatment if conventional days. Maintenance
treatment is ineffective treatment should
be individualized

120 121
 and Medical Patients
FRACTIONATED BLOOD PRODUCTS: Intravenous Immunoglobulin (IVIG)

Erythropoietin
and Subcutaneous Immunoglobulin (SCIG)

Obstetrics and Gynecology Dosing of IVIG for Obese Patients 325 Dose Calculator
http://ivig.transfusionontario.
The dose of IVIG varies depending on the org/bmi/
IVIG IN OBSTETRICS AND GYNECOLOGY 312 clinical condition. In general, the dose is
based on the patient’s weight. In the case
DIAGNOSIS EFFICACY/COMMENT DOSE of obese patients, the appropriate dosing
Anti-phospholipid Uncertain benefit 313 may Determine in regimen is unclear. It is suggested that
syndrome improve fetal outcomes when consultation with patients weighing more than 100 kg and
Aspirin® and heparin have high-risk pregnancy with a body mass index greater than
been ineffective; appropriate unit and attending 30 kg/m2 should have their IVIG dose
consultation advisable specialist calculated using an adjusted body weight.
Recurrent spontaneous Ineffective314 Not indicated The adjusted weight takes into account the

Blood Products
abortion increased volume of distribution in these

Fractionated
patients (because of increased body fluids)
In Vitro fertilization/ Ineffective315 Not indicated
without accounting for the increase in
implantation procedures
weight from body fat.
A tool which assists with the calculation
Infectious Diseases of the appropriate dose of IVIG based
on the patient’s gender, height and
IVIG IN BACTERIAL INFECTION 278,279 weight is available at
http://ivig.transfusionontario.org/bmi/.
DIAGNOSIS EFFICACY/COMMENT DOSE
Septic/Toxic Shock Recommended as an 1 g/kg on day one and Requests for IVIG for infusion in Ontario

Sickle Cell Disease

Syndrome (Group A adjunctive therapy when 0.5 g/kg on days 2 and

!
streptococcal sepsis evidence of systemic 3 or 0.15 g/kg per day Requests for IVIG for infusion are required A T T E N T I O N
with hypotension inflammation and end organ over 5 days to be submitted on the Request Form IVIG in Ontario can only
and multi-organ hypoperfusion with fever, prescribed by the MOHLTC. The form be requested using the
failure) 316,317,318,319 tachycardia, tachypnea and and the protocol for its use are posted prescribed request form.
hypotension at www.transfusionontario.org.
Necrotizing fasciitis 320,321 Possibly recommended for Adjunctive treatment
severe invasive group A in rapidly progressing
FACTORS IN CHOOSING IVIG OR SCIG
streptococcal disease if other disease 1-2 g/kg over
approaches have failed 6 hours INTRAVENOUS IMMUNOGLOBULIN (IVIG) SUBCUTANEOUS IMMUNOGLOBULIN (SCIG)
u Good maintenance of clinical u Clinical response not well maintained
Sepsis in patients in No large randomized controlled Not recommended
critical care 316,317,322,323 trials to confirm benefit for use benefit u Adverse effects of IVIG
u Local reactions to SCIG u Poor venous access
u
n Bone marrow transplant and red cell aplasia due to Patient uncomfortable with u Able to manage home or
home or self-medication self-medication
parvovirus B19: see Hematology.
n Specific hyper-immune globulins are available from u Patient prefers convenience of home
Canadian Blood services for the listed conditions: self-injection
u Varicella-Zoster Immune Globulin (VZIG)

u Hepatitis B Immune Globulin (HBIG;BayHepB)

u Anti-RSV Immune Globulin (Respigam®)

u Cytomegalovirus Immune Globulin (CMVIG, Cytogam®) 324

122 123
 and Medical Patients
Erythropoietin
FRACTIONATED BLOOD PRODUCTS: Prothrombin Complex Concentrates

A Basics 326,327 B Monitoring & Infusion Practices for Octaplex® and Beriplex® 326

Prothrombin complex concentrates (PCCs) How A T T E N T I O N

are coagulation factor concentrates that n Lyophilized powder must be

!
contain factors II, VII, IX, X. The amount Vitamin K should be given
reconstituted for administration.
intravenously at same time
of the individual coagulation factor levels n Final volume is 20 mL per vial which
varies with the specific preparations. as PCCs to avoid rebound
contains 500 IU of factor IX. anticoagulation.
n Can be prepared in syringe or minibag
Manufacturing
for intravenous infusion.
n The factor concentrate is made from pools
n Vitamin K 5-10 mg IV (not intramuscular
of 1,000-2,000 plasma donations.
or subcutaneously) should be
n Plasma units are tested for HIV (1 and 2),

Blood Products
administered immediately to avoid

Fractionated
hepatitis B, hepatitis C. rebound anticoagulation.
n Manufacturing processes include viral
inactivation steps. Dose326
n
INR PCC DOSE
The National Advisory Committee
Products available on Blood and Blood Products (NAC) <3 1,000 IU
n PCCs are supplied by CBS and HQ. Recommendations on dosing are 3-5 2,000 IU
n Two prothrombin complex concentrates based on the INR as detailed in
are licensed in Canada: Octaplex® and the table to the right. >5 3,000 IU
Beriplex®. n If the INR is unknown and major http://www.nacblood.ca/
bleeding is present, 2,000 IU (80mL) resources/guidelines/
COAGULATION FACTOR LEVELS (IU/ML) IN PCCS 327 should be administered. PCC-Recommendations-
n

Sickle Cell Disease

Final-2014-05-16.pdf
PRODUCT MANU- FACTOR FACTOR FACTOR FACTOR PROTEIN PROTEIN AT III HEPARIN The published NAC Recommendations
FACTURER II VII IX X C S include a table of detailed dosages
Octaplex® Octa- 31.4 16.1 22.3 24.4 12.0 22.2 0.1 6.0 based on a combination of INR and
pharma body weight, as an alternative dosing
Beriplex® CSL 31.0 16.2 28.9 41.3 17.9 21.6 0.6 0.5 strategy.
Behring n The maximum dose should not exceed
3,000 IU.

When
n Infusion rate should not exceed
3 mL/min for Octaplex® and 8 mL/min
for Beriplex®.

Storage
n Store between +2 to +25°C for Octaplex®
and room temperature (up to 25°C) for
Beriplex®.
n Freezing and light exposure may affect
product quality.

124 125
 and Medical Patients
Erythropoietin
FRACTIONATED BLOOD PRODUCTS: Prothrombin Complex Concentrates

B Monitoring & Infusion Practices for Octaplex® and Beriplex® (cont’d)

Monitor patient OFF-LABEL USES OF PCCs

n n

!
Check patient’s vital signs prior to starting, A T T E N T I O N Reversal of anti-Xa inhibitors (Rivaroxaban
15 minutes after starting, at end of and Apixiban).
Giving plasma for warfarin
transfusion and if there are any transfusion u Currently specific reversal agents are in
reversal is associated with
reactions. a 3-fold higher risk clinical trials and are not available outside
n Repeat INR immediately postinfusion of TACO.328 of clinical trials
to ensure adequate correction of INR. u PCCs at a dose of 2,000 IU (repeated in
n Effective half life of PCC is approximately 1 hour if hemostasis is not achieved) is being
6 hours. used across Canada
u Data to support its use is limited to studies

Blood Products
Fractionated
INDICATIONS FOR PCCs
in animals and human volunteers
n
u For patients with INR ≥1.5 AND
n
Emergency reversal of warfarin effect.
Reversal of anti-IIa inhibitors (Dabigitran).329
u A licensed antidote (Idarucizumab,
u “Life or limb” threatening bleeding
Praxbind®) is available in Canada
u Emergency surgery within 6 hours
u The dose of Idarucizumab is 5 g,

Give: administered in two 2.5 g bolus infusions

u Vitamin K 10mg IV each over 5 minutes, not more than
u PCC
15 minutes apart
For dosages, see table on page 125.
n
u INR ≤1.5 as individual coagulation
PCCs should NOT be administered if:

Sickle Cell Disease

PCCs should
not be given
factors are not below the level needed to correct
to maintain hemostasis coagulopathies
u Patients with coagulopathies not related other than warfarin.
to warfarin or Vitamin K deficiency as If PCCs is not effective in
they are deficient in coagulation factors reversing warfarin, then
not contained in PCCs (with the exception other etiologies should
of the off-label uses described) be considered.
u Patients with known HIT (Beriplex®

and Octaplex® both contain heparin) C H O O S E W I S E L Y

u Patient has received or will receive
PCCs should not be
recombinant Factor VIIa administered in clinical
n Clinical situations where vitamin K alone situations where vitamin K
will suffice are shown in the “Choosing alone will suffice.
Wisely” box to the right.10
n
Situation Vitamin K
Its use should be limited to life-threatening dose/route
hemorrhage and patients requiring
emergency surgery. INR >8-10, 2 mg po
no bleeding
Surgery >6 10 mg iv
hours later
Non-critical 1 mg iv
bleeding
126 127
 and Medical Patients
Erythropoietin
FRACTIONATED BLOOD PRODUCTS: RhIG

Rh(D) Immune Globulin (WinRho®) 324,330

Purpose n Complications of pregnancy requiring Rh(D)

n immune globulin:

!
Prevention of immunization in Rh(D) A T T E N T I O N
negative patients exposed to Rh(D) u Antepartum hemorrhage
Rh immunoglobulin is a
positive red cells. u Amniocentesis, chorionic villus biopsy
blood product: informed
consent is required. or cordocentesis
Dosages Available
u External version, abdominal trauma
n 120 ug (600 IU), 300 ug (1,500 IU),
u In-utero therapeutic interventions
600 ug (3,000 IU), 1,000 ug (5,000 IU),
IV or IM. u Ectopic pregnancy, intrauterine death

and stillbirth

Blood Products
Prevention of Rh(D) immunization by Rh(D) u Abortion, threatened, actual or therapeutic

Fractionated
n
positive fetal red cells in pregnancy in
Immunization with other red cell antigens:
non-sensitized Rh(D) negative females:
u Severe hemolytic disease of the fetus and
n Recommended doses:
newborn may involve many antigens other
u Prophylactic dose at 28 weeks 300 ug IV
than Rh(D), including, but not restricted
or IM to, Rh C, c, E, K and k, Fya, Jka, Jkb and S
u Post-partum, newborn Rh(D) positive
u Specific immune globulin prophylaxis is not
(including weak D), 300 ug IV or IM, available for specificities other than Rh(D)
within 72 hours of delivery (give as soon
as possible if 72 hour deadline is missed) Other indications for treatment/prophylaxis
• Quantify feto-maternal hemorrhage; with Rh(D) immune globulin:
n

Sickle Cell Disease

additional doses of RhIG required if After transfusion of platelet components
fetomaternal hemorrhage present (dose from Rh(D) positive donors.
should be calculated by using the College u ONLY to Rh(D) negative patients of
of American Pathologist’s on line calculator childbearing potential
at www.cap.org)
u The presence of “passive” anti-D
u Complications of pregnancy: complicates red cell compatibility testing
• Pregnancy before 12 weeks, 120 ug IV/IM and may delay transfusion without
• Pregnancy 12-20 weeks, 300 ug IV/IM significant benefit
• Pregnancy after 20 weeks, 300 ug IV/IM u The risk of Rh(D) immunization by
– Plus Fetal Maternal Hemorrhage (FMH)
platelet components is about 1%331,332
testing to determine if additional doses
required
Note: RhIG contains IgA at a concentration of
40 ug/mL or less.

128 129
 and Medical Patients
Erythropoietin
S I C K L E C E L L D I S E A S E

A Principles of Transfusion in Sickle Cell Disease333 B Special Transfusion Requirements

Transfusion in patients with sickle cell disease A T T E N T I O N n No special precautions are required for
presents particular challenges, both in the patients with HgbAS (sickle cell trait).

!
Indications for transfusion
practicalities of providing optimally matched in patients with sickle cell n Notify the hospital’s Blood Transfusion
red cells and in determining when transfusion A T T E N T I O N

!
disease differ significantly Service whenever a patient with
is likely to provide superior outcomes to other from other patients. sickle cell disease presents, to allow Notify blood bank
available therapeutic measures. It is therefore sufficient time to prepare specialized immediately about
important that expert consulting assistance be blood products should the need for sickle cell disease patients.
sought for the individual case. transfusion arise.

Phenotypically-matched RBCs A T T E N T I O N

Blood Products
Patients with sickle cell disease:
n

Fractionated
n Have elevated blood viscosity which may
Determine extended phenotype

!
Life-saving transfusion
(Rh, Kell, Duffy, Kidd and MNS blood should not be withheld
be exacerbated by increases in hematocrit.
groups) at first visit. Due to the high
n Are more likely to experience complications
if prophylactically
prevalence of partial antigens in this phenotype-matched RBCs
from transfusion. population, genotyping should also are not available.
be performed if possible.
The indications for transfusion in patients n In patients with no previous clinically
with sickle cell disease differ significantly significant alloantibodies, select RBCs A T T E N T I O N
A T T E N T I O N
from other patients: matched for the patient’s Rh (D,C,c,E,e) Patients with sickle cell

!
u Treatment of severe anemia: in the absence
In the absence of and Kell (K1) antigens. disease must be issued a
n
symptoms, transfusion

!
of heart failure, dyspnea, hypotension If known alloantibodies, select RBCs card with their extended
should be avoided unless

Sickle Cell Disease

or marked fatigue, transfusion should that are matched for the patient’s Rh phenotype and specificities
the hemoglobin has
be avoided unless the hemoglobin (Hgb) (D, C, c, E, e), Kell (K1), Kidd (Jka, Jkb), of any alloantibodies
decreased to <50 g/L.
has decreased to <50 g/L334 Duffy (Fya) and S (S,s) antigens, as well present. The reason for
• A rapid decrease in Hgb can be anticipated as any antigens to which the patient is and importance of the card
if the reticulocyte count falls below immunized. must be clearly explained
to the patient
250 x 109/L u Matching for Fyb in sickle cell patients

u Aim to decrease the sickle cell hemoglobin with the Fy(a-b-) phenotype is rarely
(HgbS) concentration while keeping the necessary
n
A T T E N T I

!
O N
total Hgb below 100 g/L in patients with If there is not sufficient time or
sickle cell complications335 Never transfuse a sickle cell resources to determine the patient’s
• Augmentation of oxygen delivery in patient to a hemoglobin phenotype, contact other hospitals
>100 g/L. that may have transfused the patient
patients with sickle cell disease is achieved
more efficiently through decreasing the previously. (In some regions of Canada,
HgbS% than by increasing the total CBS maintains a phenotype registry
Hgb level 336 of patients with sickle cell disease.)
In Quebec, phenotype can be obtained
from the Transfusion Laboratory by
accessing the transfusion summary
in the IT system.

130 131
 and Medical Patients
Erythropoietin
S I C K L E C E L L D I S E A S E

B Special Transfusion Requirements (cont’d) D Primary indications for Transfusion

Sickledex®-negative blood THERAPEUTIC TRANSFUSION A T T E N T I O N

n RBC units which test positive by Sickledex®

!
Due to decreased lifespan of
test are from donors with sickle cell trait Aplastic Crisis
n
sickle RBCs (16-20 days),
(HgbAS). This blood is therefore safe to Most commonly due to parvovirus significant fall in Hgb will
administer to patients with sickle cell disease, B19 infection, with profound occur before the reticulocyte
but it will confound post-transfusion reticulocytopenia. count recovers.338
measurements of the patient’s HgbS% n Transfusion support may be required if
and should be avoided, if possible.337 symptomatic anemia, or if Hgb <50 g/L.
n Due to a compensatory increase in

Blood Products
C Exchange Transfusion plasma volume, transfuse slowly to

Fractionated
avoid volume overload and consider
pre-transfusion diuretic.
n Depending upon a patient’s initial Hgb, it
may not be possible to achieve a specific Sequestration crisis
target HgbS% by top-up transfusion without n Trapping of sickle erythrocytes in splenic
exceeding a total Hgb of 100 g/L. sinusoids resulting in massive, painful
n Exchange transfusion may therefore be enlargement of spleen and severe
required to meet the desired target of anemia over a period of hours.
HgbS% <30% (HgbA% >70%). n If untreated, sequestration crises cause
n Ensure patient is euvolemic before initiating death from hypovolemic shock/anemia;
an exchange. immediate transfusion often required.
n

Sickle Cell Disease

Automated red cell exchange may be n Post-transfusion hemoglobin levels
available at specialized centres. often higher than expected, suggesting
autotransfusion as sequestered RBCs
Manual/partial exchange: released back into circulation.
n A typical protocol (for children, smaller n To avoid accidental polycythemia and
comparable volumes, e.g., 10 mL/kg):335 hyperviscosity, transfuse 1 unit at a
1. Phlebotomize 1st 500 mL of whole blood time, reassessing Hgb level before
(for patients who are very anemic at administering more.
baseline [e.g., Hgb <70 g/L], a top-up
transfusion may be required before first
phlebotomy) Pediatrics
2. Bolus 500 mL of 0.9% normal saline In children, consider
3. Phlebotomize 2nd 500 mL of whole blood administering RBCs in smaller
4. Transfuse 2 units of RBCs than normal aliquots (e.g., 3-5 mL/kg).
5. Repeat as necessary to achieve target Often a single transfusion is sufficient
HgbS% (typically a 1.5 blood volume to reverse a sequestration crisis.339
exchange is necessary for first treatment;
single volume cycle may be adequate for
maintenance therapy). Note that for
patients starting with Hgb near 100 g/L,
step 4 should alternate between
transfusion of 1 and 2 units in order to
keep total Hgb from exceeding 110 g/L
132 133
 and Medical Patients
Erythropoietin
S I C K L E C E L L D I S E A S E

Progressive cholestasis
n Less commonly, patients may present with n Syndrome marked by right upper quadrant
hepatic sequestration crises, characterized by pain, extreme elevation of bilirubin and
a rapidly enlarging liver accompanied by a alkaline phosphatase, and variable elevation
decrease in hemoglobin, a rise in reticulocyte in transaminases.
count, and a conjugated hyperbilirubinemia. u May be accompanied by renal failure,

u Transfusions should also be administered thrombocytopenia, and prolonged

cautiously due to the risk of autotransfusion coagulation times
and hyperviscosity. Recurrences are u Without prompt institution of exchange
common 334 transfusion, patient may develop progressive
fulminant liver failure
Acute chest syndrome340
n
Acute chest syndrome

Blood Products
A new infiltrate on CXR in a patient with Acute ischemic stroke or retinal artery

Fractionated
with the following
sickle cell disease, associated with one or suggest need for occlusion
more symptoms of fever, cough, sputum exchange transfusion n Transfusion recommended for adult patients
production, tachypnea, dyspnea, or new- rather than top-up without other obvious stroke etiology
onset hypoxia. transfusion: (e.g., cardioembolism).339
n RBC transfusion in setting of acute u Altered mental status n In patients with hemorrhagic stroke
chest syndrome results in improved u Persistent HR secondary to underlying vasculopathy,
oxygenation.341 >125 bpm, RR implementation of regular transfusion
n “Top-up” transfusion to 100 g/L may be >30/min, temp support may be beneficial in secondary
sufficient to achieve improved oxygenation. >40 °C, or hypotension prevention once the patient has stabilized.
n In some cases progression to exchange u Arterial pH <7.35;

Sickle Cell Disease

transfusion to reduce HgbS to <30% SpO2% <88%
may be necessary. despite aggressive Pediatrics
n Some studies have observed equivalent ventilatory support
Transfusion recommended for
u Serial decline in
outcomes whether patients treated with all pediatric patients with acute
exchange transfusion (HgbS% goal of SpO2% or A-a ischemic stroke. Within 3 hours of the first
30%) or top-up transfusion (Hgb goal gradient unit of transfused RBCs, MCA flow velocity
u Fall in Hgb >20 g/L
of 100 g/L).341,342 decreases by 20%.345 Exchange transfusion
n However, other studies suggest that patients u Platelet count associated with lower recurrence rate than
receiving top-up transfusions may progress <200 x 109/L top-up transfusion.346
to requiring exchange.343 u Elevated troponin
n In absence of evidence from randomized or brain natriuretic
peptide (BNP)
controlled trials, most patients with acute
u Evidence of
chest syndrome should be transfused, with
exchange transfusions reserved for patients multiorgan failure
with more severe or rapidly progressing (e.g., renal or hepatic
disease with concerning symptoms dysfunction)
u Pleural effusions or
(see yellow box to the right).344
progressive pulmonary
infiltrates

134 135
 and Medical Patients
Erythropoietin
S I C K L E C E L L D I S E A S E

PROPHYLACTIC SURGICAL PROCEDURE TRANSFUSION MANAGEMENT

Low risk: Skin, dental, perineal, Transfusion likely not necessary
Perioperative
n
inguinal or distal extremity surgery
Due to high rates of perioperative
complications (e.g., 10% rate of acute chest Moderate risk: Abdominal, ENT or Hgb <90 g/L top up to 100 g/L;
syndrome), aggressive supportive care and close orthopedic surgery Hgb >90 g/L exchange to HgbS<60%
observation is indicated.347,348 High risk of serious co-morbidities: Exchange transfusion likely necessary
u Avoid surgery during vaso-occlusive episodes

u IV fluids if NPO ≥2 hours pre-op and continue

Intracranial, cardiovascular, or (target HgbS<30%)
intrathoracic procedures; pars
post-op until oral fluids tolerated plana vitrectomy or scleral buckling
u Maintain SpO2 >96% and encourage incentive

spirometry

Blood Products
High Stroke Risk

Fractionated
u Avoid hypothermia
n In children, transfusion is indicated for
u Favour laparoscopic approaches secondary prevention of ischemic stroke
u Post-operative prophylaxis for deep venous and for primary prevention in patients
thrombosis if immobile >24 hours with high-risk features (e.g., high middle
u Aggressive control of pain cerebral artery or internal carotid blood
u Early mobilization
flow by pediatric transcranial ultrasound).
u In the latter group, maintaining HgbS
n Low-risk procedures: transfusion likely not
<30% while keeping total Hgb <120 g/L
required.
results in a 92% reduction in stroke
n Moderate risk procedures: A recent RCT of incidence 350
n
patients undergoing predominantly moderate-
Children (ages 4-16) without significant

Sickle Cell Disease

risk surgery established the necessity of pre-
cerebral vasculopathy can be safely
operative transfusion: without transfusion, the
transitioned to hydroxyurea after 12 months
risk of serious adverse events (predominantly
of transfusion if they have no prior history
acute chest syndrome) increased from 3%
of stroke or TIA [i.e., isolated high
to 33%, with median time to onset 2-3 days
Transcranial Doppler (TCD)]. TCD should be
post-operatively.349
performed every 3 months once the switch
u The transfusion protocol in this study aimed to
to hydroxyurea has been done and an
achieve a HgbS of ~60% within 10 days of immediate restart of transfusion in the case
surgery: in patients with a Hgb of <90 g/L this of reversion.351
of ~100 g/L, whereas those with a Hgb ≥90 g/L
was achieved by a top-up transfusion to a Hgb u Transfusion and hydroxyurea need to be

overlapped by 4-9 months 352

underwent a partial exchange transfusion. A
u However, a safe alternative to transfusion
previous RCT in a similar patient population had
established that a pre-operative HgbS of ~60% has not yet been established in children who
was no less effective at preventing sickle cell have already experienced a stroke, whether
complications than a target HgbS of 30%.347 it was clinically apparent 352,353 or silent 354
n n Little evidence to guide initiation of
High-risk procedures or serious patient
comorbidities (e.g., end-stage renal disease transfusions for stroke prophylaxis in adults,
or baseline SpO2<90%): a more agressive or following primary hemorrhagic strokes.
pre-operative target HgbS of <30% is advisable. u The underlying pathophysiology for both

n Pre-operative transfusions (whether top-up thrombotic and hemorrhagic strokes in

or exchange) should be performed within sickle cell disease is likely the same 355
10 days of the surgical procedure.
136 137
 and Medical Patients
Erythropoietin
S I C K L E C E L L D I S E A S E

E Supplemental indications for transfusion

The following conditions should be managed n Transfusion support should be considered

with exchange transfusion for patients who for pregnant patients with:339
have failed non-transfusion based therapies. u A history of frequent vaso-occlusive pain
The inital therapeutic goal should be HgbS crises
<30%. u Chronic renal, pulmonary or hepatic disease

u History of recurrent fetal loss

1. Recurrent pain episodes/acute chest
syndrome u Multigestational pregnancy or evidence of

n In patients who have failed an adequate trial chronic fetal distress/intrauterine growth
of hydroxyurea, chronic transfusion support retardation

Blood Products
Fractionated
may be considered as means of decreasing
5. Pulmonary hypertension363 A T T E N T I O N

!
recurrence of vaso-occlusive pain episodes
n
A T T E N T I O N
Defined as a resting mean pulmonary

!
or acute chest syndrome.356,357 Priapism, pulmonary

catheterization of ≥25mmHg. Increased

n
Transfusion not indicated as pressure (mPAP) on right heart hypertension and malleolar
Transfusion not indicated as treatment of treatment of uncomplicated
uncomplicated acute vaso-occlusive pain ulcers may represent

≥2.5m/sec is associated with increased

acute vaso-occlusive pain tricuspid regurgitant jet velocity (TRV) complications of chronic
episodes, or for treatment of chronic pain episodes.
syndromes (e.g., avascular necrosis, intravascular hemolysis
osteomyelitis, neuropathic pain).339,358 morbidity and mortality but does not (e.g., nitric oxide depletion)
necessarily reflect pulmonary arterial rather than acute
2. Priapism hypertension (PAH). vaso-occlusion.364
n Transfusion may be of benefit for episodes n In patients with TRV of >2.5 m/s,
lasting >4 hours, unresponsive to aspiration NT-pro-BNP >160 pg/ml, or PAH confirmed

Sickle Cell Disease

of blood from the corpora cavernosa and by right heart catheterization, chronic
irrigation with dilute epinephrine.359,360 transfusion therapy should be considered
if lack of response (or contraindication)
3. Malleolar ulcers to treatment with hydoxyurea.363
n Transfusion may speed healing if no
response to bed rest, wound care, antibiotics,
hyperbaric oxygen.361

4. Pregnancy362
n Although hydroxyurea is contraindicated in
pregnancy, the role of transfusion is unclear.
n A single RCT of transfusion support to
maintain the maternal HgbS <35% did not
result in improved fetal outcomes compared
to a strategy of transfusing only if Hgb <60
g/L accompanied by a reticulocyte response
of <3%.357 However, maternal sickle cell
complications were nonetheless decreased.362

138 139
 and Medical Patients
Erythropoietin
S I C K L E C E L L D I S E A S E

F Transfusion Complications

Delayed hemolytic transfusion reactions n Enhanced hemolysis appears to involve both

n Without prophylactic phenotypic matching, transfused and autologous RBCs, and may be
30% of transfused patients with sickle cell exacerbated by further transfusion of even
disease will develop alloantibodies, two crossmatch compatible/antigen-negative
thirds of them directed towards C, E and RBCs.
K1 antigens.365 n Avoid further transfusions, if at all possible:
u Alloimmunization due in part to genetic u Treat with IVIG 2 g/kg over 2-5 days

differences in the antigens expressed on red u Accompany by high dose steroids

blood cells in the donor population (e.g., prednisolone 1 mg/kg/d x 7 days)

Blood Products
(primarily Caucasians) and recipients u Consider brief course of erythropoietin

Fractionated
n 30-50% of antibodies will be undetectable

!
A T T E N T I O N if relative reticulocytopenia 369
on retesting within the year; patients may be
Alloimmunized sickle
inadvertently challenged with subsequent Hyperviscosity
cell patients require
transfusions, resulting in delayed hemolytic n Sudden onset hypertension during or
antibody card.
transfusion reactions.337 shortly after transfusion, accompanied
n Prophylactic matching for antigens therefore by signs of congestive heart failure and
advised when selecting RBCs for sickle cell profound alterations in mental status,
patients; advance notification of blood bank including stupor, coma, seizures, or features
required. of intra-cerebral infarct or hemorrhage.370
u Prophylactic matching decreases the rate of n Risk increases if Hgb transfused above A T T E N T I O N

!
alloimmunization (from 3.0% to 0.5%/unit) 100-110 g/L in patients with SCD and

Sickle Cell Disease

but it remains an issue366 Never give a top-up
HgbS% >25%, particularly if patient
n
transfusion to a sickle cell
Due to the high frequency of partial RBC dehydrated and hypoxemic.335
patient with a hemoglobin
antigens in individuals of African ethnicity, u May also occur secondary to auto-
>100 g/L
genotyping of patients with sickle cell transfusion following transfusion
disease is highly recommended. support of sequestration crises
n Manage with emergency phlebotomy.
Hyperhemolysis367
n Defined as post-transfusion RBC destruction A T T E N T I O N Transfusional iron overload Iron
accompanied by fall in Hgb to below n Each transfused unit of RBCs delivers

!
Continuing to transfuse
pre-transfusion levels. 180 mg of iron.11
a patient with Red Blood

n
u Hemolytic indices increased from baseline, Cells =
hyperhemolysis may Significant iron overload therefore likely
occasionally accompanied by relative cause worsening after repeated top-up transfusions: may
reticulocytopenia 368 of anemia! 180 mg
eventually result in hepatic, cardiac or
u Acute: occurs less than 7 days after endocrine dysfunction.
transfusion, often with no new antibodies n Selecting fresh RBCs (<7 days old) may
detectable slow iron loading in chronically transfused
u Delayed: occurs between 1 and 4 weeks patients to a small degree.
following transfusion and often n Exchange transfusions can more effectively
accompanied by new RBC antibodies mitigate or even reverse iron loading.371

140 141
 and Medical Patients
Erythropoietin
S I C K L E C E L L D I S E A S E

n Iron chelation therapy indicated once

hepatic iron concentration >7 mg/g dry
weight, as assessed by either biopsy or
calibrated MRI scan.372
u This degree of iron loading can be

anticipated after the transfusion of more

than 70 mg/kg of iron (in adult patients,
approximately 20-30 RBC units)
u Small volume phlebotomy while receiving

hydroxyurea may be useful351

Blood Products
Fractionated
u Iron overload correlates poorly with serum

ferritin in sickle cell patients but is likely

present if serum ferritin persistently
>3,000 ng/mL 373
n Iron chelators licensed for use in Canada
include deferoxamine, deferasirox and
deferiprone.
u Referral to a centre with expertise in iron

chelation therapy advised prior to initiation

of treatment

Sickle Cell Disease

142 143
 A P P E N D I C E S

Appendices
Appendix A Appendix B
Price List Information for Physicians Treating Patients
Who Are Jehovah’s Witnesses
ITEM PRICE
n Jehovah’s Witnesses refuse n Witness patients will accept
Red blood cells* $423
transfusion of allogeneic blood most:
4 units buffy coat derived platelets $185 based on their understanding u Surgical and anesthetic

1 unit single donor (apheresis) platelets $484 of several Biblical passages, procedures promoting
which they view as prohibiting conservation
Apheresis fresh frozen plasma $375
the use of: u Diagnostic and therapeutic
4 units frozen plasma** $380 u Whole blood, including
procedures (e.g., phlebotomy,
10 units cryoprecipitate $880 predonated autologous angiography)
Tranexamic acid 2 g $14 blood (predeposit) u Pharmacological enhancement
u Red blood cells
IVIG per gram $54 of hemostasis
u White blood cells u Pharmacologic stimulation
Albumin 5% 500 mL $47
u Platelets of erythropoiesis (e.g.,
Blood group (ABO, Rh D) $10
u Plasma erythropoietin) that do not
Antibody screen $10 contain blood derivatives
n
Crossmatch (no antibody) $25 n Their religious understanding A useful discussion of the
may permit the use of products position of Jehovah’s Witnesses
Crossmatch (antibody positive patient) $30
containing fractions of plasma on blood transfusion and
Prothrombin Complex Concentrates 1,000 IU $610 related issues is available.376
or cellular components, such as:
Recominant Factor VIIa/mg $1,180 n Physicians should discuss the
u Cryoprecipitate
Anti-D 120 mcg $34 various options with individual
u Clotting factor concentrates
patients, as each person must
Anti-D 300 mcg $84 u Albumin
make a personal choice
u Intravenous immunoglobulin according to their conscience.
* This cost refers only to the acquisition cost of a unit of RBC. The cost of
delivery of a unit of blood to a patient ranges from $522 to $1,183 (US). 374 u Fibrin glue n Jehovah’s Witnesses have
** This cost refers only to the acquisition cost of plasma. The total cost u Autologous blood obtained established a network of
of plasma is $409.62 per unit or $1,608.37 per patient transfused. 375 by cell salvage Hospital Liaison Committees
(HLC) across Canada. On call
local HLC members can be
contacted through the hospital
switchboard or by contacting
the Hospital Information
Services for Jehovah’s
Witnesses. This service is
available 24 hours a day
at 1-800-265-0327.

144 145
 A P P E N D I C E S

Appendices
References

1 Waters JH, Ness PM. Patient blood management: 14 Carson JL, Guyatt G, Heddle H, et al. Clinical 28 Canadian Paediatric Society. Red blood cell 41 Goel R, Ness PM, Takemoto CM, et.al. Platelet
a growing challenge and opportunity. Transfusion practice guidelines from the AABB. Red blood cell transfusions in newborn infants: Revised guidelines. transfusions in platelet consumptive disorders are
2011; 51:902-903. transfusion thresholds and storage. JAMA 2016; Fetus and Newborn Committee. Paediatrics & Child associated with arterial thrombosis and in-hospital
316:2025-2035. Health 2002; 7:553-8. mortality. Blood 2015. 125:1470-6.
2 Markowitz MA, Waters JH, Ness PM. Patient blood
management: a primary theme in transfusion 15 Kaufman RM, Djulbegovic B, Gernsheimer T, et al. 29 Simon TL, Alverson DC, AuBuchon J, et al. Practice 42 Cid J, Lozano M. Risk of Rh(D) alloimmunization
medicine. Transfusion 2014; 54:2587. Platelet transfusion: a clinical practice guideline from parameter for the use of red blood cell transfusions: after transfusion of platelets from D+ donors to D-
the AABB. Ann Intern Med 2015; 162:205-213. developed by the Red Blood Cell Administration recipients. Transfusion 2005; 45:453.
3 Salpeter SR, Buckley JS, Chatterjee S. Impact of Practice Guideline Development Task Force of the
more restrictive blood transfusion strategies on 16 Nahirniak S, Slicheter SJ, Tanael S, et al. Guidance College of American Pathologists. Arch Pathol Lab 43 Cid J, Lozano M, Zinman A, et al. Low frequency of
clinical outcomes: A meta-analysis and systematic on platelet transfusion for patients with Med 1998; 122:130-8. anti-D alloimmunization after D-incompatible
review. Am J Med 2014; 127:124-131. hypoproliferative thrombocytopenia. Transfus platelet transfusions (ADAPT) study. Br J Haematol
Med Rev 2015; 29:3-13. 30 Kirpalani H, Whyte RK, Andersen C, et al. The 2015; 168: 598–603.
4 Segal JB, Dzik WH. Paucity of studies to support Premature Infants in Need of Transfusion (PINT)
that abnormal coagulation test results predict 17 de Gast-Bakker DH, de Wilde RBP, Hazekamp MG, study: a randomized, controlled trial of a restrictive 44 The Trial to Reduce Alloimmunization to Platelets
bleeding in the setting of invasive procedures: an et al. Safety and effects of two red blood cell (low) versus liberal (high) transfusion threshold for Study Group. Leukocyte reduction and ultraviolet B
evidence-based review. Transfusion 2005; transfusion strategies in pediatric cardiac surgery extremely low birth weight infants. J Pediatr 2006; irradiation of platelets to prevent alloimmunization
45:1413-1425. patients: a randomized control trial. Intensive Care 149:301-307. and refractoriness to platelet transfusions. N Engl J
Med 2013; 39:2011-2019. Med 1997; 337:1861-915.
5 Abdel-Wahab OL, Healy B, Dzik WH. Effect of fresh 31 Bell EF, Strauss RG, Widness JA, et al. Randomized
frozen plasma transfusion on prothrombin time 18 British Committee for Standards in Haematology, trial of liberal versus restrictive guidelines for red 45 Schiffer CA, Anderson KC, Bennett CL, et al. Platelet
and bleeding in patients with mild coagulation Blood Transfusion Task Force. Guidelines for the blood cell transfusion in preterm infants. Pediatrics transfusion for patients with cancer: clinical practice
abnormalities. Transfusion 2006; 46:1279-1285. clinical use of red blood cell transfusions. Br J 2005; 115:1685-91. guideline of the American Society of Clinical
Haematol 2001; 113:24-31. Oncology. J Clin Oncol 2001; 19:1519-1538.
6 Yang L, Stanworth S, Hopewell S, et al. Is fresh- 32 Lin JC, Strauss RG, Kulhavy JC, et al. Phlebotomy
frozen plasma clinically effective? An update of a 19 Kansagara D, Dyer E, Englander H, et al. overdraw in the neonatal intensive care nursery. 46 Phekoo KH, Hambly H, Sehey SA, et al. Audit of
systematic review of randomized clinical trials. Treatment of anemia in patients with heart disease: Pediatrics 2000; 106:E19. practice in platelet refractoriness. Vox Sang 1997;
Transfusion 2012; 52:1673-1686. a systematic review. Ann Intern Med 2013; 73:81-86.
159:746-757. 33 Venkatesh V, Khan R, Curley A, et al. How we
7 Alam A, Lin Y, Lima A, et al. The prevention of decide when a neonate needs a transfusion. 47 British Committee for Standards in Haematology.
transfusion-associated circulatory overload. 20 Wu W-C, Rathore SS, Wang Y, et al. Blood Br J Haematol 2013; 160: 421-433. Guidelines for the use of platelet transfusions.
Transfus Med Rev 2013; 27:105.112. transfusion in elderly patients with acute myocardial Br J Haematol 2003; 122:10-23.
infarction. N Engl J Med 2001; 345:1230-1236. 34 Brocato B, Holliday N, Whitehurst RM Jr, et al.
8 Ontario Regional Blood Coordinating Network. Delayed Cord Clamping in Preterm Neonates: 48 Boyum JH, Atwell, TD, Schmit GD, et al. Incidence
Ontario Intravenous Immune Globulin (IVIG) 21 Villanueva C, Colomo A, Bosch A, et al. Transfusion A Review of benefits and Risks. Obstet Gynecol and Risk Factors for Adverse Events Related to
Utilization Strategy, Ontario Ministry of Health and strategies for acute upper gastrointestinal bleeding. Surv 2016; 7139-42. Image-Guided Liver Biopsy. Mayo Clin Proc 2016.
Long-Term Care. March 31, 2012. Available at URL: N Engl J Med 2013; 386:11-21. 91:329-35.
http://transfusionontario.org/en/download/ontario- 35 Clinical practice guidelines. Appropriate use of red
intravenous-immune-globulin-ivig-utilization- 22 Hebert PC, Wells G, Blajchman MA, et al. blood cells. National Health and Medical Research 49 George JN, Woolf SH, Raskob JE, et al. Idiopathic
management-strategy/. A multicenter, randomized, controlled clinical Council, Canberra, Australia 2001. thrombocytopenia purpura: a practice guideline
trial of transfusion requirements in critical care. developed by eplicit methods for the American
9 Canadian Society for Transfusion Medicine. Ten N Engl J Med 1999; 340:409-417. 36 Spence RK. Surgical Red Blood Cell Transfusion Society of Hematology. Blood 1996; 88:3-40.
Things Physicians and Patients Should Question. Policies. Blood Management Practice Guidelines
http://www.transfusion.ca/CSTM/media/Documents/ 23 Murphy GJ, Pike K, Rogers CA et al. Liberal Conference. Am J Surg 1995; 170 (Suppl 6A):3S- 50 Development Task Force of the College of American
Choosing-Wisely-10-Things-List.pdf. or restrictive transfusion after cardiac surgery. 15S. Pathologists. Practice parameter for the use of fresh-
N Engl J Med 2015;372:997-1008. frozen plasma, cryoprecipitate and platelets. JAMA
10 Callum JL, Waters JH, Shah BH, et al. The AABB 37 Carson JL, Terrin ML, Noveck H, et al. Liberal or 1994; 271:777-781.
recommendations for the Choosing Wisely 24 Lacroix J, Hébert PC, Hutchison JS, et al. Transfusion restrictive transfusion in high-risk patients after
campaign of the American Board of Internal strategies for patients in pediatric intensive care hip surgery. N Engl J Med 2011; 365:2453-62. 51 Jones J, Engelfriet CP. Massive blood replacement.
Medicine. Transfusion 2014; 54:2344-2352. units. N Engl J Med 2007; 356:1609-19. Vox Sang 1999; 77:239-250.
38 American Society of Anesthesiologists Task Force on
11 Canadian Blood Services. Circular of Information. 25 Corwin HL, Gettinger A, Fabian TC, et al. Efficacy Blood Component Therapy. Practice Guidelines for 52 Baharoglu MI, Cordonnier C, Salman RA, et al.
https://www.blood.ca/sites/default/files/ and safety of epoetin alfa in critically ill patients. Blood Component Therapy. Anesthesiology 1996; Platelet transfusion versus standard care after acute
RedBloodCellsLeukocytesReduced.pdf N Engl J Med 2007; 357:965-976. 84:732-47. stroke due to spontaneous cerebral haemorrhage
(accessed on September 13, 2016). associated with antiplatelet therapy (PATCH): a
26 Roseff SD, Luban NLC, Manno CS. Guidelines for 39 Wells RA, Leber B, Buckstein R, et al. Iron overload randomized, open-label, phase 3 trial. Lancet 2016;
12 Gammon HM, Waters JH, Watt A, et al. Developing assessing appropriateness of pediatric transfusion. in myelodysplastic syndromes: a Canadian 387:2605-2613.
performance measures for Patient Blood Transfusion 2002; 42:1398-1413. consensus guideline. Leuk Res 2008; 32:1338-53.
Management. Transfusion 2011; 51:2500-2509. 53 British Committee for Standards in Haematology,
27 British Committee for Standards in Haematology, 40 Gattermann N. Overview of guidelines on iron Blood Transfusion Task Force. Guidelines; The
13 Expert Working Group. Guidelines for red blood cell Blood Transfusion Task Force. Transfusion guidelines chelation therapy in patients with myelodysplastic administration of blood and blood components
and plasma transfusion for adults and children. for neonates and older children. Br J Haematol syndromes and transfusional iron overload. Int J and the management of transfused patients.
CMAJ 1997; 156 (Suppl 11):S1-S24. 2004; 124:433-53. Hematol 2008; 88:24-9. Transfus Med 1999; 9: 227-238.
146 147
 A P P E N D I C E S

Appendices
54 Bakchoul T, Bassler D, Heckmann M, et al. 67 Nascimento B, Rizoli S, Rubenfeld G, et al. 79 Shroyer AL, Coombs LP, Peterson ED, et al. Society 92 Storry JR, Castilho L, Daniels G, et al. International
Management of infants born with severe neonatal Cryoprecipitate transfusion: accessing of Thoracic Surgeons. The Society of Thoracic Society of Blood Transfusion Working Group on red
alloimmune thrombocytopenia: the role of platelet appropriateness and dosing in trauma. Surgeons: 30-day operative mortality and morbidity cell immunogenetics and blood group terminology:
transfusions and intravenous immunoglobulin. Transfus Med 2011;21:394-401. risk models. Ann Thorac Surg 2003; 75:1856-1865. Cancun Report (2012). Vox Sang 2014; 107:90-96.
Transfusion 2014; 54:640–5.
68 Rossaint R, Bouillon B, Cerny V, et al. The European 80 Mahomed NN, Barrett JA, Katz JN, et al. Rates 93 Fung MK, Downes KA, Shulman IA. Transfusion
55 Sparger, K, Deschmann E ,Sola-Visner M. Platelet guidelines on management of major bleeding and and outcomes of primary and revision total hip of platelets containing ABO-incompatible plasma:
Transfusions in the Neonatal Intensive Care Unit. coagulopathy following trauma: fourth edition. replacement in the United States medicare a survey of 3156 North American laboratories.
Clinics in Perinatology 2015; 42: 613–623. Crit Care 2016; 20:100 population. J Bone Joint Surg Am 2003; 85:27-32. Arch Pathol Lab Med 2007; 131:909-16.
56 Stanworth S, Tinmouth A. Plasma transfusion and 69 Stein E, McMahon B, Kwaan H, et al. The 81 Statistics Canada. Mortality – Summary list of 94 Linden JV, Wagner K, Voytovich AE, et al.
use of albumin. In Rossi’s Principles of Transfusion coagulopathy of APL revisited. Best Pract causes, 1997. Transfusion errors in New York State: an
Medicine, 4th Ed. Simon TL, Snyder EL, Solheim BG, Res Clin Hematol 2009; 22:153-163. http://www.statcan.ca/english/freepub/84F0209XIB/ analysis of 10-years experience. Transfusion 2000;
Stowell CP, Strauss RG, Petrides M. Wiley-Blackwell, free.htm. 40:1207-1213.
Oxford, UK, 2009, 287-297. 70 Schoneville H, Honohan A, van der Watering LM, et
al. Incidence of alloantibody formation after ABO-D 82 Eichhorn JH. Prevention of intraoperative anesthesia 95 Bluemle LW Jr. Hemolytic transfusion reactions
57 American Association of Blood Banks. Technical or extended matched red blood cell transfusions: a accidents and related severe injury through safety causing acute renal failure. Serologic and clinical
Manual, 16th ed. Roback, JD: AABB, Bethesda, MD, randomized trial (MATCH) study. Transfusion 2016; monitoring. Anesthesiology 1989; 70:572-577. considerations. Post Grad Med 1965; 38:484-9.
2008. 56:311-20.
83 Physicians’ Desk Reference. Montvale, NJ: Medical 96 Davenport RD. Hemolytic transfusion reactions.
58 O’Shaughnessy DF, Atterbury C, Bolton MP, et al. 71 Heddle NM, Blajchman MA, Meyer RM, et al. A Economics, 1996. In Transfusion Reactions, 3rd Ed, Popovsky MA.
Guidelines for the use of fresh-frozen plasma, randomized controlled trial comparing the frequency AABB Press, Bethesda, MD, 2007; 1-55.
cryoprecipitate and cryosupernatant. Br J Haematol of acute reactions to plasma-removed platelets and 84 Palavecino EL, Yomtovian RA, Jacobs MR. Bacterial
2004; 126:11-28. prestorage WBC-reduced platelets. Transfusion contamination of platelets. Transfus Apher Sci 2010; 97 Heddle NM. Pathophysiology of febrile nonhemolytic
2002; 42:556-566. 42:71-82. transfusion reactions. Curr Opin Hematol 1999;
59 Roberts HR, Monroe III DM, Hoffman M. Molecular 6:420-426.
biology and biochemistry of the coagulation factors 72 Clifford L, Jia Q, Subramanian A, et al. 85 Kuehnert MJ, Roth VR, Haley R, et al. Transfusion-
and pathways. In Williams Hematology, 6th Ed. Characterizing the epidemiology of perioperative transmitted bacterial infection in the United States, 98 Geiger TL, Howard SC. Acetaminophen and
Eds Beutler E, Lichtman MA, Coller BS, Kipps TJ, transfusion-associated circulatory overload. 1998 through 2000. Transfusion 2001; 41:1493- diphenhydramine premedication for allergic and
Seligsohn U. McGraw Hill, New York 2001, Anesthesiology 2015; 122:21-28. 1499. febrile nonhemolytic transfusion reactions: good
1409-1434. prophylaxis or bad practice? Transfus Med Rev
73 Serious Hazards of Transfusion Group (SHOT). 86 U.S. Food & Drug Administration. Fatalities 2007; 21:1-12.
60 Black L, Selby R, Brnjac E, et al. Bloody Easy www.shot-uk.org. reported to FDA following blood collection and
Coagulation Simplified. Ontario Regional Blood transfusion. Annual summary for fiscal year 2009. 99 Kennedy LD, Case D, Hurd DD, et al. A prospective,
Coordinating Network. 2013. 74 U.S. Food & Drug Administration. Vaccines, Blood & http://www.fda.gov/biologicsbloodvaccines/ randomized, double-blind controlled trial of
Biologics. www.fda.gov/BiologicsBloodVaccines/ safetyavailability/reportaproblem/ acetaminophen and diphenhydramine pretransfusion
61 Lin Y, Callum JL. Emergency reversal of warfarin SafetyAvailability/ReportaProblem/ transfusiondonationfatalities/. medication versus placebo for the prevention of
anticoagulation. CMAJ 2011; 182:2004. TransfusionDonationFatalities/ucm302847 transfusion reactions. Transfusion 2008; 48:2285-
(accessed 14/09/2016). 87 Brecher ME, Hay SN. Bacterial contamination of 2291.
62 Ansell J, Hirsh J, Hylek E, et al. Pharmacology blood components. Clin Microbiol Rev 2005;
and Management of the Vitamin K Antagonists: 75 Whitaker BI, Henry RA. The 2011 National 18:195-204. 100 Wang SE, Lara PN, Lee-Ow A, et al. Acetaminophen
American College of Chest Physicians Evidence- Blood Collection and Utilization Survey. and Diphenhydramine as premedication for platelet
Based Clinical Practice Guidelines (8th Edition). Department of Health and Social Services, USA. 88 Ramirez-Arcos S, Goldman M, Blajchman MA. transfusions: a prospective randomized double-blind
Chest 2008; 133:160S-198S. www.hhs.gov/ash/bloodsafety/2011-nbcus.pdf Bacterial contamination. In Transfusion Reactions, placebo-controlled trial. Am J Hematol 2002;
(accessed 14/09/2016). 3rd Ed. Ed Popovsky, MA. Bethesda, MD: AABB 70:191-194.
63 Compendium of Pharmaceuticals and Specialties. Press, 2007; 163-206.
Vitamin K. Canadian Pharmacists Association, 76 Rebibo D, Hauser I, Slimani A, et al. The French 101 Silliman CC, Ambruso DR, Boshkov LK. Transfusion-
Ottawa 2001; 1860-1861. Haemovigilence System: organization and results 89 Blajchman, MA. Bacterial contamination and related acute lung injury (TRALI). Blood 2005;
for 2003. Transfus Apher Sci 2004; 31:145-153. proliferation during the storage of cellular blood 105:2274-2280.
64 Wilson SE, Douketis JD, Crowther MA. Treatment products. Vox Sang 1998; 74 (Suppl.2):155-159.
of warfarin-associated coagulopathy: A physician 77 Ontario Transfusion Transmitted Injuries 102 Kleinman S, Caulfield T, Chan P, et al. Toward an
survey. Chest 2001; 120:1972-1976. Surveillance System (TTISS). Ontario TTISS 90 Hong H, Xiao W, Lazarus HM, et al. Detection of understanding of transfusion related lung injury:
Program Report 2013-2014. Available at URL: septic transfusion reactions to platelet transfusion statement of a consensus panel. Transfusion 2004;
65 Bolton-Maggs P, Brook L. The use of vitamin K https://ttiss.mcmaster.ca/wp-content/uploads/ by active and passive surveillance. Blood 2016; 44:1774-1789.
for reversal of over-warfarinization in children. 2016/08/OntarioTTISS-Report-2013-2014-April- 127:496-502.
Br J Haematol 2002; 118:924. 2016-Final.pdf 103 Bux J, Sachs UJ. The pathogenesis of transfusion-
91 Public Health Agency of Canada. Guideline for related acute lung injury (TRALI). Br J Haematol
66 Callum JL, Karkouti K, Lin Y. Cryoprecipitate: the 78 Wilson R, Crouch EA. Risk assessment and investigation of suspected transfusion transmitted 2007; 136:788-799.
current state of knowledge. Transfus Med Rev comparisons. Science 1987; 236:267-270. bacterial contamination. Canada Communicable
2009; 23:177-188. Disease Report 2008; 34S1:1-8. 104 Popovsky MA, Moore SB. Diagnostic and
pathogenetic considerations in transfusion-related
acute lung injury. Transfusion 1985; 25:573-577.

148 149
 A P P E N D I C E S

Appendices
105 Middelburg RA, van Stein D, Briet E, van der Bom 117 Pineda AA, Taswell HF. Transfusion reactions 131 Menis M, Forshee RA, Anderson SA, et al. 144 Allain JP, Stramer SL, Carneiro-Proietti AB, et al.
JG. The role of donor antibodies in the pathogenesis associated with anti-IgA: Report of 4 cases Posttransfusion purpura occurrence and potential Transfusion-transmitted infectious disease. Biologics
of transfusion-related acute lung injury: a systemic and review of the literature. Transfusion 1975; risk factors among the inpatient US elderly, as 2009; 37:71-77.
review. Transfusion 2008; 48:2167-76. 15:10-15. recorded in large Medicare databases during 2011
through 2012. Transfusion 2015; 55:284-295. 145 Stramer SL, Hollinger FB, Katz LM, et al. Emerging
106 Silliman CC, Paterson AJ, Dickey WO, et al. The 118 Fox SM, Stavely-Haiber LM. Immunoglobulin A (IgA) infectious disease agents and their potential threat
association of biologically active lipids with the levels in blood products and plasma derivatives. 132 Pavenski K, Webert KE, Goldman M. Consequences to transfusion safety. Transfusion 2009; 49:1S-29S.
development of transfusion-related acute lung Immunohematol 1998; 4:5-9. of transfusion of platelet antibody: a case report and
injury: a retrospective study. Transfusion 1997; literature review. Transfusion 2008; 48:1981-1989. 146 Moore FA, Moore EE, Sauaia A. Blood Transfusion.
37:719-726. 119 Fujihara H, Yamada C, Furumaki H, et al. Evaluation An independent risk factor for postinjury multiorgan
of the in hospital hemovigilance by introduction of 133 Wallis JP, Haynes S, Stark G, et al. Transfusion- failure. Arch Surg 1997; 132:620-625.
107 Silliman CC, Boshkov LK, Mehdizadehkashi Z, et al. the information technology-based system. related alloimmune neutropenia: an undescribed
Transfusion-related acute lung injury: epidemiology Transfusion 2015; 55: 2898-2904. complication of blood transfusion. Lancet 2002; 147 Sihler KC, Napolitano LM. Complications of
and a prospective analysis of etiologic factors. Blood 360:1073-1074. massive transfusion. Chest 2010; 137:2009-20.
2003; 101:454-462. 120 DM, Hume HA. Hypotensive transfusion reactions.
In Transfusion Reactions, 3rd Ed. Ed Popovsky MA. 134 O’Brien SF, YI QL, Fan W, et al. Current incidence 148 Harvey MP, Greenfield TP, Sugrue ME, et al.
108 Eder AF, Dy BA, Perez JM, et al. The residual risk of AABB Press, Bethesda, MD, 2007; 251-274. and estimated residual risk of transfusion- Massive blood transfusion in a tertiary referral
transfusion-related lung injury at the American Red transmitted infections in donations made to hospital. Clinical outcomes and haemostatic
Cross (2008-2011): limitations of predominantly 121 Pineda AA, Vamvakas EC, Gorden LD, et al. Trends Canadian Blood Services. Transfusion 2007; complications. Med J Aust 1995; 163:356-359.
male-donor mitigation strategy. Transfusion 2013; in the incidence of delayed hemolytic transfusion 47:316-325.
reactions. Transfusion 1999; 39:1097-1103. 149 Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion
53:1442-1449. of plasma, platelets and red blood cells in a 1:1:1
135 Transfusion-associated transmission of West Nile
109 Popovsky MA, Haley NR. Further characterization of 122 Perrotta PL, Snyder EL. Non-infectious complications Virus – Arizona, 2004. MMWR September 17, vs. a 1:1:2 ratio and mortality in patients with
transfusion related acute lung injury: demographics, of transfusion therapy. Blood Reviews 2001; 2004; 53:842-844. severe trauma: the PROPPR randomized clinical
clinical and laboratory features and morbidity. 15:69-83. trial. JAMA 2015; 313:471-482.
Immunohematology 2000; 16:157-159. 136 www.blood.ca/en/blog/2016-06/whats-risk-
123 Alyea EP, Anderson KC. Transfusion-associated infection-blood-transfusion (accessed August 15, 150 Diab YA, Wong ECC, Luban NLC. Massive
110 Nakagawa M, Toy P. Acute and transient decrease graft-vs-host disease. In Transfusion Reactions, 2016). transfusion in children and neonates. Br J
in neutrophil count in transfusion-related acute lung 3rd Ed. Ed Popovsky MA. AABB Press, Bethesda, Haematol 2013; 1612:15-26.
injury: cases at one hospital. Transfusion 2004; MD, 2007; 229-249. 137 Seed CR, Wong J, Polizzotto MN, et al. The residual
risk of transfusion-transmitted cytomegalovirus 151 Chidester SJ, Williams N, Wang W, et al. A pediatric
44:1689-1694. 124 Rühl H, Bein G, Sachs UJH. Transfusion-associated massive transfusion protocol. J Trauma Acute Surg
infection associated with leucodepleted blood
111 Engelfriet CP, Reesink HW. Transfusion related graft-vs-host disease. Transfus Med Rev 2009; components. Vox Sang 2015; 10911-17. 2012; 73:1273-1277.
acute lung injury. International Forum. Vox Sang 23:62-71.
138 Thiele T, Kruger W, Zimmermann K, et al. 152 Jurkovich GJ, Greiser WB, Lutermom A, et al.
2001; 81:269-283. 125 Schroeder ML. Transfusion-Associated Graft-versus- Hypothermia in trauma victims: an ominous
Transmission of cytomegalovirus (CMV) infection
112 Popovsky MA. Circulatory overload. In Transfusion Host Disease. Br J Haematol 2002; 117:275-287. by leukoreduced blood products not tested for CMV predictor of survival. J Trauma 1987; 27:1019-1024.
Reactions, 3rd Ed. Ed Popovsky MA. AABB Press, 126 Kopolovic I, Ostro J, Tsubola H, et al. A systematic antibodies: a single-center prospective study in high- 153 Rajagopalan S, Mascha E, Na J, et al. The effects
Bethesda, MD, 2001; 331-340. review of transfusion-associated graft-versus host risk patients undergoing allogeneic hematopoietic of mild perioperative hypothermia on blood loss
disease. Blood 2015; 126:406-414. stem cell transplantation (CME). Transfusion 2011; and transfusion requirement. Anesthesiology
113 Vamvakas E, Pineda AA. Allergic and Anaphylactic 51:2620-2626.
Reactions. In Transfusion Reactions, 2nd Ed. Ed 2008;108:71-77.
127 Council of Europe: Guide to the preparation, use
Popovsky MA. AABB Press, Bethesda, MD, 2001; and quality assurance of blood components. 17th 139 O’Brien SF, Scalia V, Zuber E, et al. West Nile Virus 154 Vraets A, Lin Y, Callum JL. Transfusion-associated
83-128. Ed. Council of Europe, Strasbourg, France, 2013. in 2006 and 2007: the Canadian Blood Services’ hyperkalemia. Transfus Med Rev 2011; 25:184-196.
Cited by 129. experience. Transfusion 2010; 50:1118-1125.
114 Palmer DS, O’Toole J, Montreuil T, et al. Screening 155 Sezdi M, Bayik M, Ulgen Y. Storage effects on the
of Canadian Blood Services donors for severe 128 Serrano K, Chen D, Hansen AL, et al. The effect 140 Perkins HA, Busch MP. Transfusion–associated Cole-Cole parameters of erythrocyte suspensions.
immunoglobulin A deficiency. Transfusion 2010; of timing of gamma-irradiation on hemolysis infections: 50 years of relentless challenges and Physiol Meas 2006; 27:623-635.
50:1524-31. and potassium release in leukoreduced red cell remarkable progress. Transfusion 2010; 50:2080-
concentrates stored in SAGM. Vox Sang 2014; 2099. 156 Patient Blood Management Guidelines: Module 1.
115 Sandler SG, Eder AF, Goldman M, et al. The Critical Bleeding Massive Transfusion. National
entity of immunoglobulin A-related anaphylactic 108: 370-381, 141 Agapova M, Busch MP, Custer B. Cost-effectiveness Blood Authority, Australian Government, National
transfusion reactions is not evidence based. 129 Treleaven J, Gennery A, Marsh J, et al. Guidelines of screening the US blood supply for Trypanosoma Health and Medical Research Council. 2011.
Transfusion 2015; 55:199-204. on the use of irradiated blood components cruzi. Transfusion 2010; 50:2220-2232. www.blood.gov.au/system/files/documents/pbm-
116 Koda Y, Watanabe Y, Soejima M, et al. Simple prepared by the British Committee for Standards 142 Ironside JW. Variant Creutzfeldt-Jacob disease. module-1.pdf.
PCR detection of haptoglobin gene deletion in in Heamatology Blood Transfusion Task Force. Haemophilia 2010; 16 (Suppl.5):175-180.
Br J Haematol 2011; 152:35-51. 157 CRASH-2 trial collaborators. Effects of tranexamic
anhaptoglobinemic patients with antihaptoglobin acid on death, vascular occlusive events, and blood
antibody that causes anaphylactic transfusion 143 National Haemophilia Council. Press release:
130 McFarland JG. Posttransfusion purpura. In Haemophilia & Exposure to vCJD. transfusion in trauma patients with significant
reactions. Blood 2000; 95; 1138-1143. Transfusion Reactions, 3rd Ed. Ed Popovsky MA. haemorrhage (CRASH-2): a randomized, placebo-
http://www.nationalhaemophiliacouncil.ie/
AABB Press, Bethesda, MD, 2007; 275-299. homepage.php. Accessed December 17, 2010. controlled trial. Lancet 2010; 376:23-32.

150 151
 A P P E N D I C E S

Appendices
158 Charbit B, Mandebral L, Samain E, et al. The 171 Zauber NP, Zauber AG, Gordon FJ, et al. Iron 182 Khalafallah A, Dennisa A, Bates J, et al. 193 Goldberg MA, McCutchen JW, Jove M, et al. A
decrease in fibrinogen is an early predictor of the supplementation after femoral head replacement A prospective randomized controlled trial of safety and efficacy comparison study of two dosing
severity of postpartum hemorrhage. J Thromb for patients with normal iron stores. JAMA 1992; intravenous versus oral iron for moderate iron regimens of epoietin alfa in patients undergoing
Hemost 2007; 5: 266-273. 267:525-527. deficiency anaemia of pregnancy. J Intern Med major orthopedic surgery. Am J Orthop 1996;
2010; 268:286-295. 25:544-552.
159 Patient Blood Management Guidelines: Module 2. 172 Crosby L, Palarski VA, Cottington E, et al. Iron
Perioperative. National Blood Authority, Australian supplementation for acute blood loss anemia after 183 Gurusamy KS, Nagendran M, Broadhurst JF, et al. 194 Karkouti K, McCluskey SA, Evans L, et al.
Government, National Health and Medical Research coronary bypass surgery: a randomized, placebo- Iron therapy in adults without kidney disease. Erythropoietin is an effective clinical modality
Council. 2012. controlled study. Heart Lung 1994; 23:493-499. Cochrane Database of Systematic Reviews for reducing RBC transfusion in joint surgery.
www.blood.gov.au/system/files/documents/pbm- 2014;12:CD010640.DOI:10.1oo2/1465 1858. Can J Anesth 2005; 52:362-368.
module-2.pdf. 173 Sutton PM, Cresswell T, Livesey JP, et al. Treatment CD010640.pub 12.
of anaemia after joint replacement. A double-blind, 195 Canadian Orthopedic Perioperative Erythropoietin
160 Clevenger B, Mallett SV, Klein AA, et al. Patient randomised, controlled trial of ferrous sulphate 184 Wang C, Graham DJ, Kane RC, et al. Comparative Study Group. Effectiveness of perioperative
blood management to reduce surgical risk. Br J versus placebo. J Bone Joint Surg Br 2004; 86:31- risk of anaphylactic reactions associated with recombinant human erythropoietin in elective
Surg 2015; 102:1325-1337. 33. intravenous iron products. JAMA 2015; 314:2062- hip replacement. Lancet 1993: 341:1227-1232.
2068.
161 Karkouti K, McCluskey SA, Evans L, et al. 174 Mundy GM, Birtwistle SJ, Power RA. The effect of 196 Laupacis A. Effectiveness of perioperative epoetin
Rationalizing blood conservation by using a patient- iron supplementation on the level of haemoglobin 185 BioSyent Pharma Inc. Natural and non-prescription alfa in patients scheduled for elective hip surgery.
specific risk index. Can J Anesth 2002; 49:72A. after lower limb arthroplasty. J Bone Joint Surg Br Health Products Directorate, Health Canada. Semin. Hematol, 1996; 33 (Suppl 2):51-54.
2005; 87:213-217. Available at URL: https://health-
162 Vaclavik J, Taborsky M. Antiplatelet therapy in products.canada.ca/lnhpd-bdpsnh/ 197 Stowell CP, Jone SC, Enny C, et al. An open label,
the perioperative period. Eur J Intern Med 2011; 175 Parker MJ. Iron supplementation for anemia after info.do?licence=80033717. randomized, parallel-group study of perioperative
22:26-31. hip fracture surgery. J Bone Joint Surg Am 2010; epoetin alfa versus standard of care for blood
92:265-269. 186 Nitescu N, Bengtsson A, Bengtson JP. Blood salvage conservation in major elective spinal surgery:
163 Dineen PF, Curtin RJ, Hasty JA. A review of the with continuous autotransfusion system compared safety analysis. Spine 2009; 34:2479-85.
use of common anti-platelet agents in orthopaedic 176 Weatherall M. Oral Iron therapy for anaemia after with a haemofiltration system. Perfusion 2002:
practice. J Bone Joint Surg 2010; 92B:1186-1191. orthopaedic surgery: randomized clinical trial. 17:357-362. 198 Fergusson DA, Hebert PC, Mazer CD, et al. A
ANZ J Surg. 2004; 74:1049-1051. comparison of aprotinin and lysine analogues
164 Devereux PJ, Mrkobrada M, Sessler DI, et al. 187 Carless PA, Henry DA, Moxey AJ, et al. Cell salvage in high risk cardiac surgery. N Engl J Med 2008;
Aspirin in Patients undergoing Noncardiac Surgery. 177 Moretti D, Goede JS, Zeder C, et al. Oral iron for minimising perioperative allogeneic blood 358:2319-31.
N Engl J Med 2014; 370:1494-1503. supplements increase hepcidin and decrease iron transfusion. Cochrane Database of Systematic
absorption from daily or twice daily doses in iron Reviews 2010. Issue 4. Art. No.: CD001888. 199 Henry DA, Carless PA, Moxey AJ, et al. Anti-
165 Fowler RA, Berenson M. Blood conservation in depleted young women. Blood 2015; 126:1981- fibrinolytic use for minimising perioperative
the intensive care unit. Crit Care Med 2003; 31 DOI: 10. 1002/14651858. CD001888.pub4.
1989. allogeneic blood transfusion. [Systematic Review]
(12 Suppl):S715-S720. 188 Wang G, Bainbridge D, Martin J, et al. The efficacy Cochrane Injuries Group Cochrane Database of
178 Tolkein Z, Stecher L, Mander LP, et al. Ferrous of an intraoperative cell saver during cardiac Systematic Reviews. 2011; 3: CD 001886.
166 Douketis JD, Berger PB, Dunn AS, et al. The sulphate supplementation causes significant
Perioperative Management of Antithrombotic surgery: a meta-analysis of randomized trials.
gastrointestinal side-effects in adults: a systematic Anesth Analg 2009; 109:320-30. 200 Ferraris VA, Ferraris SP, Sha SP, et al. Perioperative
Therapy: American College of Chest Physicians review and meta-analysis. PLoS One 2015; blood transfusion and blood conservation in cardiac
Evidence-Based Clinical Practice Guidelines 10:e0117383. 189 Messmer K. Consensus statement: using epoetin surgery: the society of Thoracis Surgery and
(8th Edition). Chest 2008; 133; 299S-339S. alfa to decrease the risk of allogeneic blood Cardiovasular Anesthetists Clinical Practice
179 Bager P, Dahlerup JF. Randomized clinical trials: transfusion in the surgical setting. Semin Hematol Guidelines. Ann Thorac Surg 2007; 83:S27-S86.
167 Andrews CM, Lane DW, Bradley, JG. Iron pre-load oral vs. intravenous iron after upper gastrointestinal
for major joint replacement. Transfus Med 1997; 1996; 33 (Suppl 2):78-80.
tract haemorrhage-a placebo-controlled study. 201 Ker K, Prieto-Merino D, Roberts I. Systematic
7:281-286. Aliment Pharmacol Ther 2014; 39:176-187. 190 Dubois RW, Lim D, Hébert P, et al. The development Review, meta-analysis and meta-regression of the
168 Edwards TJ. Randomized clinical trial of preoperative of indications for the preoperative use of effect of tranexamic acid on surgical blood loss.
180 Beris P, Munoz M, Garcia-Erce JA, et al. recombinant erythropoietin. Can J Surg 1998; Br J Surg 2013;100:1271-1279.
intravenous iron sucrose to reduce blood transfusion Perioperative anaemia management: consensus
in anaemic patients after colorectal cancer surgery. 41:351-365.
statement on the role of intravenous iron. 202 Ker K, Roberts I, Shakur H, et al. Antifibrinolytic
Br J Surg 2009; 96:1122-1128. Br J Anaesth 2008; 100:599-604. 191 Faris PM, Spence RK, Larholt KM, et al. The drugs for acute traumatic injury. Cochrane Database
169 Lidder PG. Pre-operative oral iron supplementation predictive power of baseline haemoglobin for of Systemic Reviews 2015 Issue 5 Art.No.CD
181 Kim YH, Chung HH, Kang SB, et al. Safety and transfusion risk in surgery patients. Orthopedics, 004896.
reduces blood transfusion in colorectal surgery-a usefulness of intravenous iron sucrose in the
prospective, randomized, controlled trial. Ann R Coll 1999; 22 (1, suppl):S135-S140.
management of preoperative anemia in patients 203 Wei Z, Liu M. The effectiveness and safety of
Surg Engl 2007; 89:418-421. with menorrhagia: a phase IV, open-label, 192 Feagan BG, Wong CJ, Kirkley A, et al. Erythropoietin tranexamic acid in total hip or knee arthroplasty:
170 Quinn M, Drummond RJ, Ross F, et al. Short course prospective, randomized study. Acta Haematol with iron supplement to prevent allogeneic blood a meta-analysis of 2720 cases. Transfus Med 2015;
pre-operative ferrous sulphate supplementation – 2009; 121:37-41. transfusion in total hip joint arthroplasty. Ann Intern 25:151-162.
is it worthwhile in patients with colorectal cancer? Med 2000; 133:845-854.
Ann R Coll Surg Engl 2010; 92:569-72.

152 153
 A P P E N D I C E S

Appendices
204 Shemshaki H, Sayed MAN, Nourian N, et al. 215 Simpson E, Lin Y, Stanworth S et al. Recombinant 228 Bohlius J, Tonia T, Schwarzer G. Twist and Shout: 240 Bari K, Minano C, Shea M et al. The combination
One step closer to sparing total blood loss and factor VIIa for the prevention and treatment of One Decade of Meta-Analyses of Erythropoiesis- of octreotide and midodrine is not superior to
transfusion rate in total knee arthroplasty: a meta- bleeding in patients without haemophilia. Cochrane Stimulating Agents in Cancer Patients. Acta albumin in preventing recurrence of ascites after
analysis of different methods of tranexamic acid Database of Systematic Reviews 2012; 14 Haematol 2011; 125:55-67. large-volume paracentesis. Clin Gastroenterol
administration. Arch Orthop Trauma Surg 2015; Mar.DOI10.1002/14651858.CD005011.pub4. Hepatol 2012; 10:1169-1175
135:573-588. 229 Rizzo JD, Brouwers M, Hurley P, et al. American
216 Faris PM, Ritter MA. Epoietin Alfa. A bloodless Society of Clinical Oncology/American Society of 241 Becker G, Galandi D, Blum HE. Malignant ascites:
205 Compendium of Pharmaceuticals and Specialties. approach for the treatment of perioperative Hematology Clinical Practice Guideline Update Systematic review and guideline for treatment.
Canadian Pharmacists Association, Ottawa, 2003: anemia. Clin Orthop 1998; 357:60-67. on the Use of Epoetin and Darbepoetin in Adult EJC Review 2006; 42:589-597.
Cyklokapron (Tranexamic acid). Patients With Cancer. J Clin Oncol 2010; 28:4996-
217 Beutler E. Production and destruction of 5010. 242 Sort P, Navasa M, Arroyd V, et al. Effect of
206 Carless PA, Henry DA, Moxey AJ, et al. erythrocytes. In Williams Hematology, 6th Ed. intravenous albumin on renal impairment
Desmopressin for minimizing perioperative Eds Beutler E, Lichtman MA, Coller BS, et al. 230 Tonia T, Mettler A, Robert N, et al. Erythropoietin and mortality in patients with cirrhosis and
allogeneic blood transfusions. Cochrane Database McGraw Hill, New York, 2001; 355-368. or darbepoetin for patients with cancer. Cochrane spontaneous bacterial peritonitis. N Engl J Med
Syst Rev 2004; 1:CD001884. Database Syst Rev. 2012;12:CD003407. doi: 1999; 341:403-409.
218 Janssen-Ortho Inc. Product monograph. EPREX® 10.1002/14651858.CD003407.pub5.
207 Levi M, Cromheecke ME, de Jonge E, et al. sterile solution. Revised September 22, 2010. 243 Uriz J, Gines P, Cardenas A, et al. Terlipressin plus
Pharmacological strategies to decrease excessive 231 Margarson MP, Soni N. Serum albumin: touchstone albumin infusion: an effective and safe therapy of
blood loss in cardiac surgery: a meta-analysis of 219 Barrett BJ, Fenton SS, Ferguson B, et al. Clinical or totem? Anesthesia 1998; 53:789-803. hepatorenal syndrome. J Hepatol 2000; 33:43-48.
clinically relevant endpoints. Lancet 1999; 354; practice guidelines for the management of anemia
1940-1947. co-existent with chronic renal failure. Canadian 232 Boldt J. The good, the bad and the ugly: should 244 Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A
Society of Nephrology. J Am Soc Nephrol 1999; we completely banish human albumin from our randomized, prospective, double-blind, placebo-
208 Society of Thoracic Surgeons Blood Conservation 10 (Suppl 13):S292-S296. intensive care units. Anesth Analg 2000; 91:887- controlled trial of terlipressin for type 1 hepatorenal
Guideline Task Force. 2011 update to the Society 895. syndrome. Gastroenterology 2008; 134:1360-8.
of Thoracic Surgeons of Cardiovascular 220 Clinical practice guidelines and clinical practice
Anesthesiologists blood conservation clinical recommendations for anemia in chronic kidney 233 Plasbumin®-25 package insert. Grifols, Revised 245 Martin-Llahi M, Pepin MN, Guevara M, et al.
practice guidelines. Ann Thorac Surg 2011; disease in adults. Am J Kidney Dis2006 May; September 2014. Terlipressin and albumin vs albumin in patients with
91:944-82. 47 (5 Suppl 3):S16-85. cirrhosis and hepatorenal syndrome: a randomized
234 Howard G, Downward G, Bowie D. Human serum study. Gastroenterology 2008; 134:1352-9.
209 Bignami E, Cattaneo M, Crescenzi G, et al. 221 Cody JD, Hodson EM. Recombinant human albumin induced hypotension in the post-operative
Desmopressin after cardiac surgery in bleeding erthropoietin versus placebo or no treatment phase of cardiac surgery. Anaesth Intensive Care 246 Angeli P, Volpin R, Gerunda G, et al. Reversal
patients. A multicenter randomized trial. Acta for the anaemia of chronic kidney disease in 2001; 29:591-594. of type 1 hepatorenal syndrome with the
Anesthesiol Scand 2016; 60:892-900. people not requiring dialysis. Cochrane Database administration of midodrine and octreotide.
Syst Rev 2016; 1: CD003266. 235 Bernardi M, Carcini P, Navikis RJ, et al. Albumin Hepatalogy 1999; 29:1690-1697.
210 Rodgers A, Walker N, Schug S, et al. Reduction of infusion in patients undergoing large volume
postoperative mortality and morbidity with epidural 222 Pfeffer MA, Burdmann EA, Chen CY, et al. A trial paracentesis: a meta-analysis of randomized trials. 247 Cavallin M, Kamath PS, Merli M. Terlipressin plus
or spinal anesthesia: results from overview of of darbepoetin alfa in type 2 diabetes and chronic Hepatoloy 2012; 55:1172-1181. albumin versus midodrine and ocredotide plus
randomized trials. BMJ 2000; 321:1493-1497. kidney disease. N Engl J Med 2009; 361:2019-32. albumin in the treatment of hepatorenal syndrome;
236 Runyon BA. AASLD Practice Guidelines Committee. a randomized trial. Hepatology 2015; 62:567-574.
211 Menkis AH, Martin J, Cheng DCH. Drugs, 223 Singh AK, Szczech L, Tang KL, et al. Correction of Management of adult patients with ascites due
devices, technologies and techniques for blood anemia with epoetin alfa in chronic kidney disease. to cirrhosis: an update. Hepatology 2009; 248 Cochrane Injuries Group Albumin Reviewers. Human
management in minimally invasive and conventional N Engl J Med 2006; 355:2085-98. 49:2087-107. albumin administration in critically ill patients:
cardiothoracic surgery. Innovations 2012; systematic reviews of randomized controlled trials.
224 Levin A, Hemmelgarn B, Culleton B, et al. Clinical 237 Graziotto A, Rossaro L, Inturri P, Salvagnini M. BMJ 1998; 317:235-240.
7:229-241. guidelines: guidelines for the management of Reinfusion of concentrated ascitic fluid versus total
212 Carless PA, Henry DA, Anthony DM. Fibrin sealant chronic kidney disease. CMAJ 2008; 179:1154-116. paracentesis. A randomized prospective trial. Dig 249 The SAFE Study Investigators. A comparison of
use for minimising peri-operative allogeneic blood Dis Sci 1997; 42:1708-14. albumin and saline for fluid resuscitation in the
225 Kauffman JS, Reda DJ, Fye CL, et al. Subcutaneous intensive care unit. N Engl J Med 2004; 350:2247-
transfusion. Cochrane Database of Systematic compared with intravenous epoetin in patients 238 Singh V, Dheerendra PC, Singh B, et al. Midodrine
Reviews 2003. Issue 2. Art. No.: CD004171. 2256.
receiving hemodialysis. N Engl J Med 2001; versus albumin in the prevention of paracentesis –
DOI: 10. 1002/14651858. CD004171. 339:578-583. induced circulatory dysfunction in cirrhotics: a 250 Annane D, Siami S, Jaber S, et al. Effects of fluid
213 Compendium of Pharmaceuticals and Specialties. randomized pilot study. Am J Gastroenterol 2008; resuscitation with colloids vs. crystalloids on
226 Aronson N, Bohn R, Finkelstein B, et al. Use of 103:1399-405. mortality in critically ill patients presenting with
Canadian Pharmaceutical Association, Ottawa epoetin for anemia of chronic renal failure. Agency
2011. Thrombin alfa (recombinant) (Recothrom); hypovolemic shock: The CRISTAL randomized trial.
for Healthcare Research and Quality, Rockville, MD. 239 Lata J, Marecek Z, Fejfar T, et al. The efficacy of JAMA 2013:310 1809-1817.
2095. Publication No. 01-E016, 2001. www.ahrq.gov. terlipressin in comparison with albumin in the
214 Alayash A. Blood substitutes; why haven't we prevention of circulatory changes after the 251 Wilkes MM, Navickis RJ. Patient survival after
227 Madore F, White CT, Foley RN, et al. Clinical paracentesis of tense ascites – a randomized human albumin administration. Ann Intern Med
been more successful. Trends Biotechnol 2014; practice guidelines for assessment and management
32:177-185. multicentric study. Hepatogastroenterology 2007; 2001; 135:149-164.
of iron deficiency. Kidney International. 2008; 54:1930-3.
74 (Suppl 110):S7-S11.

154 155
 A P P E N D I C E S

Appendices
252 Cooper AB, Cohn, SM, Zhang HS, et al. Five percent 266 Ontario Regional Blood Coordinating Network. 279 United Kingdom Clinical Guidelines for 290 Feasby T, Banwell B, Benstead T, et al. Guidelines
albumin for adult burn shock resuscitation: Lack of Ontario Intravenous Immune Globulin Infusion Immunoglobulin Use. 2nd Ed. 2011. United on the use of intravenous immune globulin for
effect on daily multiple organ dysfunction. Guide and Adverse Reaction Chart, Kingdom Department of Health. www.gov.uk. neurological conditions. Transfus Med Rev 2007;
Transfusion 2006; 46:80-89. http://transfusionontario.org/en/download/ontario- 21 (Suppl.1):S57-S107.
intravenous-immune-globulin-infusion-guide-and- 280 Shehata N, Palda V, Brown N, et al. The use of
253 Greenhalgh DG. Burn resuscitation: the results of adverse-reaction-chart/. immunoglobulin therapy for patients with primary 291 Kuitwaard K, de Gelder J, Tio-Gillen A, et al.
the ISBI/ABA survey. Burns 2010; 36:176-82. immune deficiency: an evidence based practice Pharmacokinetics of intravenous immunoglobulin
267 Ontario Regional Blood Coordinating Network. guideline. Transfus Med Rev 2010; 24 (Suppl.1): and outcome in Guillain-Barre syndrome. Ann
254 Pham TN, Cancio LC, Gibran NS. American Burn IVIG Dose Calculator. S28-S50. Neurol 2009;66:597-603.
Association Practice Guidelines, burn shock http://www.transfusionontario.org/dose/.
resuscitation. J Burn Case Res 2008; 29:257-266. 281 Shehata N, Falda VA, Meyer RM, et al. The use of 292 Huges R, Donofrio P, Bril V, et al. Intravenous
268 Kleinman S. Adverse reactions to IVIG. In IVIG immunoglobulin therapy for patients undergoing immune globulin (10% caprylate-chromatography
255 Silver GM, Klein MB, Herndon DN, et al. Standard Utilization Management Handbook 1st Ed. BC solid organ transplantation: an evidence based purified) for the treatment of chronic inflammatory
operating procedures for the clinical management Provincial Blood Coordinating Office 2002; 7-10. practice guideline. Transfus Med Rev 2010; demyelinating polyradiculoneuropathy (ICE study):
of patients enrolled in a prospective study of 24 (Suppl.1):S7-S27. a randomised placebo-controlled trial. Lancet 2008;
inflammation and the host response to thermal 269 Duhem C, Dicato MA, Ries F. Side-effects of 7:136-144.
injury. J Burn Case Res 2007; 28:222-230. intravenous immune globulins. Clin Exp Immunol 282 Peraldi M, Akposso K, Hayman J, et al.
1994; 97 (Suppl 1):79-83. Long-Term Benefit of Intravenous Immunoglobulins 293 Merkies I Bril V, Dalakas M, et al. Health-related
256 Van der Sande FM, Kooman JP, Barendregt JN, in Cadaveric Kidney Retransplantation. quality-of-life improvements in CIPD with immune
et al. Effect of intravenous saline, albumin, or 270 Pierce LR, Jain N. Risks associated with the use of Transplantation 1996; 62:1670-1673. globulin IV 10%: The ICE Study. Neurology 2009;
hydroxyethylstarch on blood volume during intravenous immunoglobulin. Transfus Med Rev 72:1337-1344.
combined ultrafiltration and hemodialysis. 2003; 17:241-251. 283 Casadei D, del C. Rial M, Opelz G, et al.
J Am Soc Nephrol 1999; 10:1303-1308. Randomized and Prospective Study Comparing 294 Baumann A, Hess C, Sturzenegger M. IVIg dose
271 Stiehm ER. Adverse effects of human Treatment with High-Dose Intravenous increase in mulifocal motor neuropathy. Neurology
257 Knoll A, Grabowski JA, Dervin GF, et al. A immunoglobulin therapy. Transfus Med Rev 2013; Immunoglobulin with Monocloncal Antibodies 2009; 256:608-614.
randomized controlled trial of albumin versus 27:171-178. for Rescue of Kidney Grafts with Steroid-Resistant
saline for the treatment of intradialytic hypotension. Rejection. Transplantation 2001; 71:53-58. 295 Zinman L, Ng E, Bril V. IV immunoglobulin in
J Am Soc Nephrol 2004; 15:487-492. 272 Bharath V, Eckert K, Kang M, et al. Incidence and patients with myasthenia gravis: A randomized
natural history of intravenous immunoglobulin- 284 Jordan S. Evaluation of Intravenous Immunoglobulin controlled trial. Neurology 2007; 68:837:841.
258 Denault AY, Belisle S, Hardy J. Fluid management in induced aseptic meningitis; a retrospective review as an Agent to Lower Allosensitization and Improve
major surgery. In Fluid management in the acutely at a single tertiary care centre. Transfusion 2015; Transplantation in Highly Sensitized Adult Patients 296 Gajdos P. Treatment of Myasthenia Gravis
ill. An evidence-based educational program. Ed 55:2597-2605 with End-Stage Renal Disease: Report of the NH Exacerbation with Intravenous Immunoglobulin.
Sibbald WJ, et al. Core Health Services Inc 2001; IG02 Trial. Nephrol 2004; 15:3256-3262. Arch Neurol 2005; 62:1689.
87-111. 273 Padmore R. Possible mechanisms for intravenous
immunoglobulin-associated hemolysis: clues 285 Roberts D, Jiang S, Chadban S. The Treatment of 297 Barth D, Nabavi Nouri M, Ng E, et al. Comparison
259 Martin GS, Moss M, Wheeler AP, et al. A obtained from review of clinical case reports. Acute Antibody-Medicated Rejection in Kidney of IVIg and PLEX in patients with myasthenia gravis.
randomized, controlled trial of furosemide with or Transfusion 2015; 55(Suppl.2):S59-S64. Transplant Recipients – A Systematic Review. Neurology 2011; 76:2017-2023.
without albumin in hypoproteinemic patients with Transplantation 2012; 94:775-783.
acute lung injury. Crit Care Med 2005; 33:1681-7. 274 Pendergrast J, Willie-Ramharack K, Sampson L, 298 Barnett C, Wilson G, Barth D et al. Changes
et al. The role of inflammation in immune globulin 286 Anderson D, Ali K, Blanchette V, et al. Guidelines in quality of life scores with intravenous
260 Martin GS, Mangialardi RJ, Wheeler AP, et al. mediated hemolysis. Transfusion 2015; 55:2597- on the Use of Intravenous Immune Globulin for immunoglobulin or plasmapheresis in patients
Albumin and furosemide therapy in hypoproteinemic 2605. Hematologic Conditions. Transfus Med Rev 2007; with myasthenia gravis. J Neurol Neurosur
patients with acute lung injury. Crit Care Med 2002; 21:S9-S56. Psychiatry. 2012; 84:94-97.
30:2175-82. 275 Ammann EM, Jones MP, Link BK, et al. Intravenous
immune globulin and thromboembolic adverse 287 Neuert C, Lim W, Crowther M, et al. The American 299 Titulaer M, McCracken L, Gabilondo I, et al.
261 Pi D, Petraszko T. IVIG supply and cost. In IVIG events in patients with hematologic. Malignancy. Society of Hematology 2011 evidenced-based Treatment and prognostic factors for long-term
Utilization Management Handbook 1st Ed, BC Blood 2016; 127: 200-207. practice guideline for immune thrombocytopenia. outcome in patients with antiNMDA receptor
Provincial Blood Coordinating Office 2002;1:3. Blood 2011; 117:4190-4207. encephalitis: an observational cohort study.
276 Bresee JS, Mast EE, Coleman PJ, et al. Hepatitis C Lancet Neurol 2013; 12:157-165.
262 CSL Behring, personal communication April 4, 2011. virus infection associated with administration of 288 American Academy of Pediatrics Clinical Practice
intravenous immune globulin. JAMA 1996; Guideline. Management of hyper-bilirubinemia in a 300 Kampylafka E, Kosmidis ML, Panagrotakos DB
263 Canadian Blood Services Data. 276:1563-1567. et al. The effect of intravenous immunoglobulin
newborn infant 35 or more weeks of gestation.
264 www.pptaglobal.org/images/source/2014/FALL/2. Pediatrics 2004; 114:297-316. (IVIG) treatment on patients with dermatomyositis:
277 Agarwal S, Cunningham-Rundles C. Treatment of A 4-year follow-up study. Clin Exp Rheumatol.
Clinical need.pdf (accessed 16 August, 2016.). hypogammaglobulinemia in adults: a scoring system 289 Cordonnier C, Chevret S, Legrand M, et al. Should 2012;30:397-401.
265 Foster PR, Welch AG, McLean C, et al. Studies on to guide decisions on immunoglobulin replacement immunoglobulin therapy be used in allogeneic stem-
the removal of abnormal prion protein by processes therapy. J Allergy Clin Immunol 2013; 131:1699- cell transplantation? A randomized, double-blind, 301 Shojania K. Topics in adult rheumatology. In IVIG
used in the manufacture of human plasma products. 1701. placebo-controlled, multicenter trial. Ann Intern Med Utilization Management Handbook 1st Ed. BC
Vox Sang 2000; 78:86-95. 2003; 139:8-18. Provincial Blood Coordinating Office April 2002,
278 Intravenous Immunoglobulin (IVIG) Utilization 64-67.
Management Program Guideline. British Columbia
Provincial Blood Coordinating Office, Provincial
Health Authority 2014. www.pbco.ca.
156 157
 A P P E N D I C E S

Appendices
302 Schroeder JO, Zeuner RA, Euler HH, et al. High 314 Daya S, Gunby J, Porter F, et al. Critical analysis of 327 Kalina U, Bickhard H, Schulte S. Biochemical 339 Josephson CD, Su LL, Hillyer KL, et al. Transfusion in
dose intravenous immunoglobulins in systemic intravenous immunoglobulin therapy for recurrent comparison of seven commercially available the patient with sickle cell disease: a critical review
lupus erythematosus: clinical and serological results miscarriage. Hum Reprod Update 1999; 5:475-482. prothrombin complex concentrates. Int J Clin of the literature and transfusion guidelines. Transfus
of a pilot study. J Rheumatol 1996; 23:71-75. Pract 2008; 62:1614-1622. Med Rev 2007; 21:118-133.
315 Stephenson MD, Fluker MR. Treatment of repeated
303 Boletis JN, Ionnidis JP, Boki KA, et al. Intravenous unexplained in vitro fertilization failure with 328 Sarode R, Milling TJ, Rejaai MA, et al. Efficacy 340 Howard J, Hart N, Roberts-Harewood M, et al.
immunoglobulin compared with cyclophosphamide intravenous immunoglobulin: a randomized and safety of a 4-factor prothrombin complex Guideline for the management of acute chest
for proliferative lupus nephritis. Lancet 1999; placebo-controlled Canadian trial. Fertil Steril concentrate in patients on vitamin K antagonists syndrome in sickle cell disease. Br J Haematol 2015;
354:569-570. 2000; 74:1108-1113. presenting with major bleeding: a randomized 169:492-505.
plasma-controlled phase lllb study. Circulation 2013;
304 Newburger J, Takahashi M, Burns J, et al. 316 Werdan K. Intravenous immunoglobulin for 128:1234-1243. 341 Vichinsky EP, Neumayr LD, Earles AN, et al. Causes
The Treatment of Kawasaki Syndrome with prophylaxis and therapy of sepsis. Curr Opin and outcomes of the acute chest syndrome in sickle
Intravenous Gamma Globulin. N Engl J Med 1986; Crit Care 2001; 7:354-361. 329 Pollack CV, Reilly PA, Eikelboom J, et al. cell disease. National Acute Chest Syndrome Study
315:341-347. Idaruczimab for Dabigitran reversal. N Engl Group. N Engl J Med 2000; 342:1855-1865.
317 Alejandria MM, Lansang MA, Dans LF, et al. J Med 2015; 373:511-520.
305 Barron K, Murphy D, Silverman E, et al. Treatment Intravenous immunoglobulin for treating sepsis 342 Turner JM, Kaplan JB, Cohen HW, et al. Exchange
of Kawasaki Syndrome: A comparison of two and septic shock. Cochrane Data Base Syst Rev, 330 Qureshi, H, Massey E, Kirwan D, et al. BCSH versus simple transfusion for acute chest syndrome
dosage regimens of intravenously administered 2003, Issue 3. guidelines for the use of anti-D immunoglobulin for in sickle cell anemia adults. Transfusion 2009;
immune globulin. J Pediatr 1990; 117:638-644. the prevention of haemolytic disease of the fetus 49:863-868.
318 Kaul R, McGeer A, Norby-Teglund A, et al. and newborn. Transfus Med 2014; 24: 8-20.
306 Newburger J, Takahashi M, Beiser A, et al. Intravenous immunoglobulin therapy for 343 Wayne AS, Kevy SV, Nathan DG. Transfusion
A Single Intravenous Infusion of Gamma Globulin streptococcal septic shock syndrome – a 331 Cid J, Lozano M, Ziman A, et al. Low frequency management of sickle cell disease. Blood 1993;
as Compared with Four Infusions in the Treatment comparative observational study. Clin Infect of anti-D alloimmunization following D+ platelet 81:1109-1123.
of Acute Kawasaki Syndrome. N Engl J Med 1991; Dis 1999; 28:800-807. transfusion: the anti-D alloimmunization after
324:1633-1639. D-incompatible platelet transfusions (ADAPT) 344 Johnson CS. The acute chest syndrome. Hematol
319 Darenberg J, Ihendyana N, Sjolin J, et al. study. Br J Haematol 2015; 168: 598-603. Oncol Clin North Am. 2005; 19:857-79, vi-vii.
307 Terai M, Shulman S. Prevalence of coronary artery Intravenous immunoglobulin G therapy in
abnormalities in Kawaski disease in highly streptococcal toxic shock syndrome: a European 332 Weinstein R, Simard A, Ferschke J, et al. Prospective 345 Venketasubramanian N, Prohovnik I, Hurlet A,
dependent on gamma globulin dose but randomized, double-blind, placebo-controlled trial. surveillance of D- recipients of D+ apheresis et al. Middle cerebral artery velocity changes during
independent of salicylate dose. J Pediatr 1997; Clin Infect Dis 2003; 37:341-343. platelets: alloimmunization against D is not transfusion in sickle cell anemia. Stroke 1994;
131:888-893. detected. Transfusion 2015; 55: 1327-1330. 25:2153-2158.
320 Haywood CT, McGeer A, Low DE. Clinical
308 Shulman ST. Recommendations for the use of experience with 20 cases of group A streptococcus 333 Yawn BP, Buchanan G, Afenyi-Annan AN, et al. 346 Hulbert ML, Scothorn DJ, Panepinto JA, et al.
intravenous immunoglobulin therapy in Kawasaki necrotizing fasciitis and myonecrosis: 1995-1997. Management of sickle cell disease: summary of Exchange blood transfusion compared with simple
disease. Pediatr Infect Dis J 1992; 11:985-6. Plast Reconst Surg 1999; 108:1567-1573. the 2014 evidence based report by expert panel transfusion for first overt stroke is associated with
members. JAMA 2014; 1033-1048. a lower risk of subsequent stroke: a retrospective
309 Barron SJ, DelVecchio MT, Aronoff C. Intravenous 321 Seal DV. Necrotizing fasciitis. Curr Opin Infect cohort study of 137 children with sickle cell anemia.
immunoglobulin in the treatment of Stevens- Dis 2001; 14:127-132. 334 National Institutes of Health. The Management J Pediatr 2006; 149:710-712.
Johnson syndrome and toxic epidermal necrolysis: a of Sickle Cell Disease, 4th Ed. revised June 2002.
meta-analysis and meta-regression of observational 322 Chow A. Topics in infectious diseases. In IVIG NIH National Heart, Lung and Blood Institute. 347 Vichinsky EP, Haberkern CM, Neumayr L, et al.
studies. Inter J Dermatol 2015; 54:108-115. Utilization Management Handbook 1st Ed. BC NIH Publication No. 02-2117. A comparison of conservative and aggressive
Provincial Blood Coordinating Office, April 2002; http://www.nhlbi.nih.gov/health/prof/blood/ transfusion regimens in the perioperative
310 Engineer I, Ahmed AR. Emerging treatment for 90-100. sickle/sc_mngt.pdf [accessed Nov 20 2010]. management of sickle cell disease. The Preoperative
epidermolysis bullosa acquisita. J Am Acad Dermatol Transfusion in Sickle Cell Disease Study Group.
2001; 44:818-828. 323 Pildal J, Gotzsche PC. Polyclonal immunoglobulin for 335 Swerdlow PS. Red cell exchange in sickle cell N Engl J Med 1995; 333:206-213.
treatment of bacterial sepsis: a systematic review. disease. Hematology Am Soc Hematol Educ
311 Ahmed AR, Dahl MD. Consensus statement on the Clin Infect Dis 2004; 39:38-46. Program 2006:48-53. 348 Steinberg MH. Management of Sickle Cell
use of intravenous immunoglobulin therapy in the Disease. N Engl J Med 1999; 340:1021-1028.
treatment of autoimmune mucocutaneous blistering 324 Clinical Guide to Transfusion 2006:44-45. 336 Alexy T, Pais E, Armstrong JK, et al. Rheologic
diseases. Arch Dermatol 2003; 139:1051-1059. https://professionaleducation.blood.ca/en/ behavior of sickle and normal red blood cell 349 Howard J, Malfroy C, Llewelyn L, et al. The
transfusion/clinical-guide-transfusion. mixtures in sickle plasma: implications for transfusion alternatives preoperatively in sickle cell
312 Stephenson MD. Topics in obstetrics and transfusion therapy. Transfusion 2006; 46:912-918. disease (TAPS) study. A randomized, controlled,
gynecology. In IVIG Utilization Management 325 Sigel J. Immunoglobulins and Obesity. Pharmacy multicentre clinical trial Lancet. 2013; 381:930-938.
Handbook 1st Ed. BC Provincial Blood Coordinating Practice News 2010; 37:01. 337 Vichinsky EP. Current issues with blood
Office, April 2002, 81-89. transfusions in sickle cell disease. Semin 350 Adams RJ, McKie VC, Hsu L, et al. Prevention of
326 National Advisory Committee on Blood and a first stroke by transfusions in children with sickle
Blood Products. Recommendations for use of Hematol 2001; 38:14-22.
313 Scoble T, Wijetilleka S, Khamashta MA. cell anemia and abnormal results on transcranial
Management of refractory anti-phospholipid Prothrombin Complex Concentrates in Canada 338 Saarinen UM, Chorba TL, Tattersall P, et al. Doppler ultrasonography N Engl J Med. 1998;
syndrome. Autoimmun Rev 2011; 10:669-673. 2014. www.nacblood.ca/resources/guidelines/ Human parvovirus B19-induced epidemic acute 339:5-11.
PCC-recommendations-final-2014-05-16.pdf. red cell aplasia in patients with hereditary
hemolytic anemia. Blood 1986; 67:1411-1417.

158 159
 A P P E N D I C E S

Appendices
351 Ware RE, Schultz WH, Davis BR, et al. 362 Malinowski AK, Shehata N, D'Souza R, et al. 373 Raghupathy R, Manwani D, Little JA. Iron overload
Hydroxycarbamide versus chronic transfusion for Prophylactic transfusion for pregnant women in sickle cell disease. Adv Hematol 2010;
maintenance of transcranial doppler flow velocities with sickle cell disease: a systematic review and 2010:272940.
in children with sickle cell anaemia-TCD With meta-analysis. Blood 2015; 126:2424-35.
transfusions Changing to Hydroxyurea (TWiTCH): 374 Shander A, Hofmann A, Ozawa S, et al. Activity
a multicentre, open-label, phase 3, non-inferiority 363 Klings ES, Machado RF, Barst RJ, et al. An based costs of blood transfusions in surgical
trial Lancet. 2016; 387:661-670. official American Thoracic Society Clinical Practice patients at four hospitals. Transfusion 2010;
Guideline: diagnosis, risk stratification, and 50:753-65.
352 Ware RE, Helms RW. Stroke with transfusions management of pulmonary hypertension in sickle
changing to hydroxyurea (SWiTCH) Blood 2012; cell disease. Am J Respir Crit Care Med 2014; 375 Shander A, Ozawa S, Hofmann A. Activity-based
119:3925-3932. 189:727-740. costs of plasma transfusions in medical and surgical
patients at a US hospital. Vox Sang 2016; 111:55-
353 Adams RJ, Brambilla D. Optimizing Primary 364 Kato GJ, McGowan V, Machado RF, et al. 61
Stroke Prevention in Sickle Cell Anemia (STOP 2) Lactate dehydrogenase as a biomarker of hemolysis-
Trial Investigators. Discontinuing prophylactic associated nitric oxide resistance, priapism, leg 376 Bodnaruk ZM, Wong CJ, Thomas MJ. Meeting the
transfusions used to prevent stroke in sickle cell ulceration, pulmonary hypertension, and death clinical challenge of care in Jehovah’s Witnesses.
disease. N Engl J Med 2005; 353:2769-2778. in patients with sickle cell disease. Blood 2006; Transfus Med Rev 2004; 18:105-116.
107:2279-2285.
354 DeBaun MR, Gordon M, McKinstry RC, et al.
Controlled trial of transfusions for silent cerebral 365 Vichinsky EP, Earles A, Johnson RA, et al.
infarcts in sickle cell anemia. N Engl J Med2014; Alloimmunization in sickle cell anemia and
371:699-710. transfusion of racially unmatched blood.
N Engl J Med 1990; 322:1617-1621.
355 Prengler M, Pavlakis SG, Prohovnik I, et al. Sickle
cell disease: the neurological complications. Ann 366 Vichinsky EP, Luban NLC, Wright E, et al.
Neurol 2002; 51:543-552. Prospective RBC phenotype matching in a stroke-
prevention trial in sickle cell anemia: a multicentre
356 Miller ST, Wright E, Abboud M, et al. Impact of transfusion trial. Transfusion 2001; 41:1086-1092.
chronic transfusion on incidence of pain and acute
chest syndrome during the Stroke Prevention Trial 367 Danaee A, Inusa B, Howard J, et al. Hyperhemolysis
(STOP) in sickle-cell anemia. J Pediatr 2001; in patients with hemoglobinopathies: a single-centre
139:785-789. experience and review of the literature. Transfus
Med Rev 2015; 29:220-230.
357 Koshy M, Burd L, Wallace D, et al. Prophylactic
red-cell transfusions in pregnant patients with 368 Win N, New H, Lee E, et al Hyperhemolysis
sickle cell disease. A randomized cooperative syndrome in sickle cell disease: case report
study. N Engl J Med 1988; 319:1447-1452. (recurrent episode) and literature review.
Transfusion 2008; 48:1231-1238.
358 Wanko SO, Telen MJ. Transfusion management in
sickle cell disease. Hematol Oncol Clin North Am 369 Win N, Sinha S, Lee E, Mills W. Treatment with
2005; 19:803-26, v-vi. intravenous immunoglobulin and steroids may
correct severe anemia in hyperhemolytic transfusion
359 Walker EM, Mitchum EN, Rous SN, et al. reactions: case report and literature review.
Automated erythrocytopheresis for relief of Transfus Med Rev 2010; 24:64-67.
priapism in sickle cell hemoglobinopathies.
J Urol 1983; 130:912-916. 370 Johnson CS. Arterial blood pressure and
hyperviscosity in sickle cell disease. Hematol
360 Mantadakis E, Ewalt DH, Cavender JD, Rogers ZR, Oncol Clin North Am 2005; 19:827-37.
Buchanan GR. Outpatient penile aspiration and
epinephrine irrigation for young patients with sickle 371 Kim HC, Dugan NP, Silber JH, et al.
cell anemia and prolonged priapism. Blood 2000; Erythrocytapheresis therapy to reduce iron
95:78-82. overload in chronically transfused patients with
sickle cell disease. Blood1994; 83:1136-1142.
361 Chernoff AI, Shapleigh JB, Moore CV. Therapy of
chronic ulceration of the legs associated with sickle 372 Olivieri NF. Progression of iron overload in sickle
cell anemia. JAMA1954; 155:1487-1491. cell disease. Semin Hematol 2001; 38:57-62.

160 161
 Red Blood Cell Pre-Transfusion Checklist

Alternatives failed or q Anemia investigations completed (e.g., CBC, blood film,

have been ordered? ferritin, iron saturation, vitamin B12, reticulocyte count)

q Iron (oral and IV), vitamin B12, erythropoietin ordered

Bloody Easy Blood Administration
Bloody Easy Blood Administration or not indicated
handbook is ideal for nurses or
Patient advised of risks of:
q TACO 1 in 100
healthcare professionals Consent?
administering blood. It provides
an overview of blood and blood q Hemolytic reaction 1 in 7,000
q TRALI 1 in 10,000
products, the risks associated with

q Major allergic reaction 1 in 40,000

them, and how they should be
administered. In addition, it
describes the types of transfusion q Bacterial infection 1 in 250,000
reactions that may occur.
Female under 45? q Order Kell-negative units
q Inform recipient of the potential risk of transfusion causing
Bloody Easy Coagulation hemolytic disease of the newborn in future pregnancies

Bloody Easy Coagulation Order irradiated blood if patient has any history of the following:
q Hodgkin’s lymphoma
At risk for FATAL
handbook provides practical
transfusion-
q Allogeneic or autologous stem cell transplant
information on Coagulation.
associated Graft vs.
It is designed to enhance the
q Ever treated with fludarabine, cladribine, bendamustine,
Host Disease?
knowledge of physicians,
nurses and medical laboratory alemtuzumab, anti-thymocyte globulin (ATG)

q Congenital immunodeficiencies
technologists about the basics
of coagulation from laboratory
testing to anticoagulant drugs Does my patient have a history of:
q Age greater ≥70 years
Diuretics?
and management of common

q Renal dysfunction
bleeding disorders.

q Left ventricular dysfunction

q Prior or current CHF
q Severe euvolemic anemia (hemoglobin <50 g/L)

q If YES to any of the above: prescribe PO/IV furosemide

pre-transfusion (unless currently hypovolemic)

q Specify rate of infusion (default rate is over 2 hours per unit;

Design and layout by Hope Creative Inc., Toronto, Ontario
Rate and Dose?
Published by Ontario Regional Blood Coordinating Network inpatients and patients at risk for TACO (need diuretics) infuse
over 3-4 hours)

q Order 1 unit at a time (unless bleeding)

Printed in Canada

ISBN 978-0-9869176-2-2 TACO: Transfusion-Associated Circulatory Overload, TRALI: Transfusion-Related Acute Lung Injury,
CHF: Congestive Heart Failure