Core Curriculum in Nephrology

Therapeutic Plasma Exchange: Core

Curriculum 2023
C. Elena Cervantes, Evan M. Bloch, and C. John Sperati

Complete author and article

From producing individual blood components for transfusion to the removal of pathogenic substances, information provided at end
apheresis is a cornerstone of modern medical therapies. The use of therapeutic plasma exchange of article.
(TPE), in which plasma and its soluble constituents are removed from the body in exchange for a
replacement fluid, can be organ- and life-saving in many diseases. Given the notable similarities Am J Kidney Dis.
81(4):475-492. Published
be- tween TPE and hemodialysis, the nephrologist is often responsible for managing TPE. As online February 10, 2023.
such, one
doi: 10.1053/
must be familiar with the technologies, approach to therapy, indications for use, and
j.ajkd.2022.10.017
complications. TPE uses centrifugation or membrane separation technologies, with the latter
able to be performed with certain hemodialysis machines familiar to the nephrologist. Furthermore, © 2022 by the National
primary kidney diseases such as anti–glomerular basement membrane disease are frequently Kidney Foundation, Inc.
associated with autoantibodies, potentially making them ideal candidates for TPE. Nevertheless,
the use of TPE in many kidney dis-
eases is controversial because of the lack of supporting evidence. This review discusses TPE from

Introduction clinical application, and lingering uncertainties.

It has long been postulated that removal of
pathogenic substances from the blood may be
therapeutic or even curative for some diseases.
Phlebotomy dates to ancient times, and, in the
modern era, technology has evolved to enable
separation of specific blood components. The
term apheresis refers to the general technique of
extracorporeal removal of a blood constituent.
As the name suggests, plasmapheresis removes
plasma from a patient, whereas therapeutic
plasma exchange (TPE) entails removing
plasma from the patient in exchange for
replacement fluid. Table 1 describes different
apheresis modalities based on target
molecule.
TPE is an extracorporeal therapy performed
using centrifugation or membrane filtration.
Notably, the ideal characteristics of a
substance to be removed by TPE include
large molecular weight, distribution in the
intravascular space, and prolonged half-life,
among others. As the nephrologist is often
responsible for managing TPE, one must
understand the indications, how to write the
prescription, selection of replace- ment fluid,
appropriate use of anticoagulation, and
monitoring for and treating procedural
complications. With the exception of
anti–glomerular basement membrane (GBM)
disease, in which the evidence of benefit is
acceptably clear, data supporting the use of
TPE for many kidney diseases have been
mixed.

Additional Reading
➢ McLeod BC. Therapeutic apheresis: history,
AJKD Vol 81 | Iss 4 | April 2023 1
 Transfusion. clinical trials have largely used
2010;50(7):1413- centrifugation, the specific modality used
1426. https:// often varies by country. Most TPE sessions in
doi.org/10.1111/ the United States are centrifugation-based.
j.1537-
2995.2009.0250 Centrifugation FEATURE EDITOR
5. Melanie Hoenig
The centrifuge is the functional unit of this
continuous-flow extracorporeal circuit and ADVISORY BOARD
Technique does not require a blood-membrane interface. By Ursula C.
spinning at 2,000-2,500 revolutions per minute, Brewster
Two technologies it separates the components of anticoagulated Michael J. Choi
are available for the Biff F. Palmer
removal of plasma Bessie Young
and its pathogenic
substance(s): The Core
Curriculum aims to
centrifugation and
give trainees in
membrane nephrology a
filtration. strong knowledge
Membrane base in core topics
filtration TPE can in the specialty
only separate by providing an
over- view of the
plasma, whereas topic and citing
centrifugation TPE key references,
can frac- tionate any including the
of the blood
components (eg,
erythrocytes,
platelets, plasma).
As such,
centrifugation TPE
is the apheresis
modality employed
when specific blood
fractions are
targeted. Both
methods are
similarly effective at
removing plasma
proteins, and each
in- volves
administration of
replacement fluid at
an equal or greater
volume to what
was removed. As
shown in Table 2,
however,
membrane
filtration TPE
extracts a smaller
fraction of plasma
(30%) per unit of
time than
centrifugal systems
(80%), requiring
longer treatment
times and higher
blood flow rates.
This can increase
the risk for circuit
clotting. Although

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 Cervantes et al

Table 1. Apheresis Modalities

(polyethylene with γ-ray sterilization) and the Prismaflex
ProcedureTarget Molecule TPE series (polypropylene with ethylene oxide steriliza-
Adsorptive cytapheresis Monocytes, granulocytes tion), although other filters are available worldwide.
ß2-microglobulin column ß2-microglobulin Certain models of continuous kidney replacement therapy
Double filtration plasmapheresis Autoantibodies, immune (CKRT) and intermittent hemodialysis machines are
complexes, lipoproteins compatible with these filters. The separation efficiency
Erythrocytapheresis Red blood cells
depends on plasma filtration rates, membrane properties
Extracorporeal photopheresis Buffy coat (white
such as pore size and surface area, and the sieving co-
blood
cells and platelets) efficients. The latter is a measure of equilibration of a given
Immunoadsorption Immunoglobulins solute between the filtrate and blood sides of the mem-
Leukocytapheresis White blood cells brane, thereby indicating how effectively a molecule is
Lipoprotein apheresis Lipoprotein particles moved across the filter. Sieving coefficients depend on
Red blood cell exchange Red blood cells (exchanged molecule factors such as size, protein binding, and charge.
for replacement fluid) Serum protein adsorption to the membrane will lead to
Rheopheresis High-molecular-weight filter clogging and decreased separation.
plasma components Similar to CKRT modalities that rely on convective
(fibrinogen, α2-macro-
globulin, low-density clearance, high ultrafiltration rates lead to high filtration
lipoprotein fractions, and red blood cell damage and/or filter
cholesterol, and IgM) clotting may occur as the hematocrit level increases.
Therapeutic plasma exchange Plasma (exchanged for Therefore, membrane filtration TPE is limited to a filtration
replacement fluid) fraction of 30%-35% of the plasma, requiring longer
Thrombocytapheresis Platelets treatment ses- sions and higher blood flow rates.
Abbreviation: IgM, immunoglobulin M.
Consequently, mem- brane filtration TPE requires
central venous access.
Unlike hemodialysis or hemofiltration, which removes
substances of low to medium molecular weight from
serum, TPE targets larger-molecular-weight substances
blood according to density. Consequently, the blood sep-
arates around the axis of rotation, with plasma in the present in plasma (Table 2).
innermost layer, then granulocytes (ie, buffy coat),
monocytes, lymphocytes, platelets, and finally red blood Additional Readings
cells in the outermost layer (Fig 1). ➢ Ward DM. Conventional apheresis therapies: a review. J
Centrifugation can pack red blood cells to a hematocrit Clin Apher. 2011;26(5):230-238. https://doi.org/10.1
level of ≥80%, allowing for removal of larger plasma 002/jca.20302
volumes and shorter sessions. Furthermore, because lower ➢ Williams ME, Balogun RA. Principles of separation: in-
blood flow rates are sufficient, peripheral vein access can dications and therapeutic targets for plasma exchange.
be used for centrifugation TPE. Clin J Am Soc Nephrol. 2014;9(1):181-190. https://doi.
org/10.2215/CJN.04680513 +ESSENTIAL READING
Membrane Filtration ➢ Hafer C, Golla P, Gericke M, et al. Membrane versus
centrifuge-based therapeutic plasma exchange: a ran-
Similar in concept to isolated ultrafiltration in dialysis,
plasma constituents are nonselectively removed across a domized prospective crossover study. Int Urol Nephrol.
semipermeable membrane. The two membrane separation 2016;48(1):133-138. https://doi.org/10.1007/s11255-
filters marketed in the United States are the Plasmaflo OP 015-1137-3

Table 2. Apheresis Versus Hemodialysis

Therapeutic Plasma Exchange
Characteristic Centrifugation Membrane Filtration Hemodialysis
Mechanism Centrifugal force Convection Diffusion and/or convection
Blood flow, mL/min 10-150 150-200 Continuous: 100-300;
intermittent: 200->400
Blood volume in circuit, mL 180 125 160-280
Plasma extraction, % 80 30 NA
Molecular weight cutoff, Da >15,000 >15,000 <15,000
Vd, L/kg Low (<0.3) Low (<0.3) Moderate (≤1.5-2)
Protein binding, % >80 >80 <80
Anticoagulation Citrate Heparin Heparin
Sterilization γ-Irradiation; ethylene γ-Irradiation; ethylene Ethylene oxide; steam;
oxide oxide electron beam; γ-irradiation
Abbreviations: NA, not applicable; Vd, volume of distribution.

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 Cervantes et al

Figure 1. Comparison of centrifugation and membrane separation therapeutic plasma exchange (TPE). In centrifugation TPE, blood is re
filtration upon return to the patient. Figure created with Biorender.com.

➢ Gashti CN. Membrane-based therapeutic plasma ex- Its use should be most strongly considered in those
change: a new frontier for nephrologists. Semin Dial. conditions for which there is evidence to support clinical
2016;29(5):382-390. https://doi.org/10.1111/ benefit. Table 3 describes common plasma proteins and
sdi.12506 +ESSENTIAL READING their characteristics.
➢ Kes P, Janssens ME, Baˇsi´c-Juki´c N, Kljak M. A
ran- domized crossover study comparing membrane Vascular Access
and centrifugal therapeutic plasma exchange Most apheresis devices use centrifugation and require
procedures. Transfusion. 2016;56(12):3065-3072. blood flow rates of 50-120 mL/min, compared with 150-
https://doi.org/1 0.1111/trf.13850 200 mL/min in membrane filtration TPE (Table 2). The
➢ Ahmed S, Kaplan A. Therapeutic plasma exchange us- TPE procedure can be continuous, which requires access
ing membrane plasma separation. Clin J Am Soc Nephrol. and return catheters, or discontinuous, which allows a
2020;15(9):1364-1370. https://doi.org/10.2215/ single catheter to serve for access and return. A discon-
CJN.12501019 +ESSENTIAL READING tinuous setup requires longer procedure times.
Procedure-related factors (urgency, volume[s]
exchanged, frequency), patient-related factors (underlying
Basic Principles and General Considerations disease, mental status, and vascular anatomy), and insti-
tutional capabilities determine the ideal vascular access.
When to Consider TPE
Options include the following.
TPE is most commonly used to target a single
pathogenic substance for removal from the plasma. The Large-Bore Peripheral Intravenous Access
ideal char- acteristics of such substances include large In adults, 17-19–gauge needles are used; these are used to
molecular weight (>15,000 Da), slow rate of formation, supply blood flow rates ranging from >80 to 60 mL/min.
prolonged half-life, higher-percentage intravascular In children, 19-22–gauge needles are used. Routinely,
distribution, and low turnover rate. Nevertheless, within blood is withdrawn from the basilic or cephalic vein and
specific dis- eases, TPE has not always demonstrated returned with replacement fluid to smaller veins in the
clinical benefit. hands.

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Table 3. Distribution and Metabolism of Plasma Proteins

Plasma Concentratio n, Mass, Intravascular, Fractional Turnover, Half-Life,
Protein mg/mL kDa % %/d d
IgA 2.6 160 42 25 6
IgD 0.02 175 75 37 2.8
IgE 0.0001 190 41 94 2.5
IgG 12.1 150 45 6.7 22
IgM 0.9 950 78 19 5
Albumin 42 65 40 10 17
Fibrinogen 2-4 340 80 25 4.2
C3 1.5 240 63 56 2
Abbreviation: Ig, immunoglobulin.
Adapted with permission of the copyright holder from Kaplan, 1999 (A Practical Guide to Therapeutic Plasma Exchange; Blackwell Science); original materials ©1999
John Wiley and Sons.

Central Venous Catheters for Dialysis the method of apheresis, comorbid processes (eg,
In adults, 11.5-F catheters provide consistent and reliable cirrhosis, kidney failure, or thrombocytopenia), and the
blood flow rates and are usually placed into the internal need for systemic anticoagulation for other indications
jugular or femoral veins. (eg, extracorporeal membrane oxygenation [ECMO]).
There are 2 standard anticoagulant agents used to maintain
Ports the patency of the circuit, citrate and heparin.
Ports are subcutaneous chambers with a distal tip that
terminates at the junction of the right atrium and the Citrate
su- perior vena cava. Often, a single-lumen 9-F port is used Citrate is the preferred agent because of its regional effect,
for access (ie, blood draw) with blood and replacement short half-life (30-60 min), and excellent safety profile.
fluid return via peripheral intravenous (IV) access. Dual- Citrate is infused in the circuit before the pump, where it
lumen ports typically have flow rates similar to large- chelates ionized calcium to prevent activation of the coag-
bore pe- ripheral IV accesses. Ports are associated with low ulation cascade. In centrifugation TPE, the risk of citrate
infection rates and provide greater patient comfort. For toxicity is low because 80% is removed with the
central venous catheters (CVC) and port patency, heparin discarded plasma. Membrane filtration TPE, however,
locks at 1,000 U/mL are often used. requires higher blood flow rates and clears only 20%-30%
of the citrate. This increases the risk for citrate toxicity,
Arteriovenous Fistulas or Grafts particularly in patients with liver or kidney disease, and
Arteriovenous fistulas (AVFs) or arteriovenous grafts heparin is preferred with this modality. Calcium must be
(AVGs) are excellent choices for patients undergoing replaced orally or IV to avoid systemic hypocalcemia.
ongoing, repetitive TPE because these accesses provide fast The most commonly used commercial citrate solutions are
blood flow, low risk of infection, and excellent long-term Anticoag- ulant Citrate Dextrose Formula A (ACD-A),
patency. This is the access of choice particularly for he- which is a hy- pertonic solution (sodium concentration of
modialysis recipients who need TPE. AVFs are used in only 252 mmol/L), and ACD-B, which is isotonic to plasma.
2%-4% of apheresis procedures. Given the time needed for Whole blood to anticoagulant ratios of 10:1-14:1
creation and maturation, they are not suitable for patients (expressed in milliliters) are commonly used. The ratio may
requiring urgent or short courses of therapy. be adjusted to deliver more anticoagulant agent if
platelet clumping occurs, while monitoring for increased
Additional Readings citrate reactions.
➢ Ipe TS, Marques MB. Vascular access for therapeutic
plasma exchange. Transfusion. 2018;58(suppl 1):580- Heparin
589. https://doi.org/10.1111/trf.14479 Heparin is inexpensive, has a short half-life (23 minutes to
➢ Barth D, Sanchez A, Thomsen AM, et al. Peripheral 2.48 hours), and is almost entirely cleared during TPE. A
vascular access for therapeutic plasma exchange: a practical bolus of 3,000-5,000 U is administered at the start of
approach to increased utilization and selecting the most treatment, followed by 1,000 U/h if needed. Heparin is the
appropriate vascular access. J Clin Apher. 2020;35(3):178- preferred anticoagulant agent in membrane filtration TPE,
187. https://doi.org/10.1002/jca.21778 and the clot- ting risk is low enough that initial treatment
without anti- coagulation can be considered with modern
Anticoagulation equipment.
Anticoagulation is used to prevent clotting in the extra- There is considerable institutional variability in the
corporeal circuit. The specific anticoagulant depends on management of patients already receiving anticoagulation.
For patients receiving a heparin drip and undergoing
centrifugation TPE, one approach is to discontinue the

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drip

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 Cervantes et

1 hour before TPE with citrate infusion. Treatment of pa- combination can be
tients currently receiving warfarin, low-molecular-weight
heparin, or direct oral anticoagulant agents may be chal-
lenging because of longer drug half-lives, less availability
of reversal agents, and reduced ability to easily monitor
the bleeding risk. TPE with albumin replacement is safe
to perform in individuals receiving warfarin, although
albu- min replacement increases the anticoagulant effect
through removal of clotting factors. At many institutions,
TPE is performed in the standard fashion with citrate or
heparin in patients receiving preexisting anticoagulation.
Finally, in patients with small blood volumes (eg, pe-
diatric patients), many centers use a combination of
ACD-A and heparin (eg, 500 mL ACD-A with 10,000 U
heparin) to minimize the amount of citrate, although a
whole blood to anticoagulant ratio of at least 26:1 is
used.
Additional Readings
➢ Lee G, Arepally GM. Anticoagulation techniques in
apheresis: from heparin to citrate and beyond. J Clin
Apher. 2012;27(3):117-125. https://doi.org/10.1002/
jca.21222 +ESSENTIAL READING
➢ Zantek ND, Morgan S, Zantek PF, Mair DC, Bowman
RJ, Aysola A. Effect of therapeutic plasma exchange on
coagulation parameters in patients on warfarin. J Clin
Apher. 2014;29(2):75-82.
https://doi.org/10.1002/jca.21294
➢ Daugirdas JT, Blake PG, Ing TS. Handbook of Dialysis, 5th
ed. Wolters Kluwer Health; 2015.
➢ Kaplan A, Raut P, Totoe G, Morgan S, Zantek ND.
Management of systemic unfractionated heparin anti-
coagulation during therapeutic plasma exchange. J Clin
Apher. 2016;31(6):507-515. https://doi.org/10.1
002/jca.21441
➢ Shunkwiler SM, Pham HP, Wool G, et al. The man-
agement of anticoagulation in patients undergoing
therapeutic plasma exchange: a concise review. J Clin
Apher. 2018;33(3):371-379. https://doi.org/10.1
002/jca.21592 +ESSENTIAL READING
Replacement Fluids
The choice of replacement fluid depends on the indication
for apheresis, as well as infection and bleeding risks.
Replacement fluids consist of colloids, crystalloids, or a
combination of the 2, although crystalloids are typically
only used for hyperviscosity syndrome. Human albumin
solution is used most frequently for its oncotic properties.
Albumin
Commercially available 5% albumin solutions contain
approximately 145 mmol/L sodium and <2 mmol/L po-
tassium. TPE followed by albumin replacement will
result in a 50%-60% reduction in pro- and anticoagulant
factors. Fortunately, rebound is biphasic, with an initial
increase 4 hours after pheresis and almost complete
recovery by 48 hours. Coagulation testing should not be
performed for 8- 12 hours after albumin replacement. If
cost is a limitation, an 80:20 albumin–saline solution

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 Cervantes et al
used, with a minimum ratio of 70:30. These diluted (c) One plasma volume exchanged every other day
replacement fluids carry a higher risk for hypotension, and (d) One plasma volume exchanged daily
use is commonly limited to hyperviscosity syndrome.
Because albumin is heat-inactivated, it has a lower risk
than plasma of hypersensitivity reactions, transfusion-
related acute lung injury, and transmission of
infection.
Frozen Plasma
Plasma is primarily used to replenish ADAMTS13 in
thrombotic thrombocytopenic purpura (TTP) and clotting
factors in patients with bleeding (eg, diffuse alveolar
hem- orrhage [DAH]). Frozen plasma is typically fresh
frozen plasma or 24-hour frozen plasma. Three or more
sessions of daily TPE may require replacement with 2-4 U
fresh frozen plasma (500-1,000 mL) to reduce the
bleeding risk, although monitoring coagulation studies
to guide this practice is preferred. Frozen plasma contains
approximately 7 mmol citrate per unit, increasing the risk
for citrate toxicity with large-volume infusions. Moreover,
because unit size is 200-300 mL, a single plasma volume
exchange of 3 L will require 10-15 U obtained from this
many donors.
To prevent allergic reactions, patients are often
pretreated with diphenhydramine despite data showing
no benefit of preprocedure antihistamine. If there is a
history of sensitivity to fresh frozen plasma, solvent
detergent plasma (pathogen- inactivated blood product) or
pretreatment with steroids, diphenhydramine, and
ephedrine has been used successfully. Risks associated
with donor plasma include transfusion re- actions and
citrate toxicity. There is a higher rate of infection
transmission in low- and middle-income countries,
whereas the risk is extremely low in high-income
countries.

Prescribing Principles
Case 1: A 50-kg, 42-year-old woman presents with fatigue
and headache of 2 weeks’ duration. In the emergency
department, she is ill-appearing with heart rate of 115
beats/ min and blood pressure 120/65 mm Hg. She has a
petechial rash. Laboratory results include hematocrit
level of 18%,
platelet count of 12 × 103/μL, serum creatinine (Scr) level of
1.3 mg/dL (from a baseline of 0.8 mg/dL), lactate dehydro-
genase level of 2,100 U/mL, and haptoglobin level of <6 mg/
dL. A peripheral blood smear shows 15% schistocytes.

Question 1: You decide to initiate TPE for treatment of

likely TTP while awaiting results of ADAMTS13 activity.
What is the estimated plasma volume (EPV) to be
exchanged?
(a) 2.7 L
(b) 3.7 L
(c) 4.7 L
(d) 5.7 L
Question 2: Which one of the following is the most
appropriate initial prescription?
(a) Two plasma volumes exchanged every other day
(b) Two plasma volumes exchanged daily

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 Cervantes et

0.9

Question 3: Which one of the following replacement 0.8

fluids would be most appropriate? 0.7

(a) Frozen plasma 0.6

(b) Albumin 0.5
(c) Combination of albumin and frozen plasma

% of initial
0.4
(d) 0.9% saline solution 0.3

For the answers to these questions, see the following text. 0.2
0.1
0
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 2.0
Writing the Prescription Ve/EPV

The average blood volume in adults is 6.5% of body

Figure 2. The relationship of percentage decrease in initial con- centratio
weight (w5 L), of which 60% is plasma (w3 L). EPV can Therapeutic Plasma Exchange; Blackwell Science).
be calculated from estimated blood volume
(0.065 × weight in kilograms) and hematocrit as
EPV = (0.065 × weight) × (1 − hematocrit).
There are numerous formulas and “rules of thumb” for
this calculation, and apheresis machines use a modified
formula that includes patient sex, height, and weight to
estimate the exchange volume. of 1 indicates perfect equilibration across a membrane
One plasma volume exchange removes a fixed propor- and a need for fewer TPE sessions, whereas a solute with
tion (approximately 65%-70%) of the targeted substance a sieving coefficient of 0 does not cross at all.
from the intravascular compartment. Equilibration across • Plasma half-life (also expressed as t1/2): Substances with a
body fluid compartments determines the net clearance of shorter half-life may be synthesized more rapidly, lead-
the substance, represented by the equation X1 = X0 − Ve/ ing to faster rebound and need for more frequent TPE.
EPV, where X1 represents the final plasma concentration, X 0 Conversely, an exogenous substance with a short half-life
the initial concentration, and Ve the volume exchanged. will have faster clearance even in the absence of TPE.
As Ve/EPV increases, however, the incremental decrease • Extravascular concentration: Substances with large
in the initial concentration of the targeted substance also extravascular distribution will be removed more slowly
decreases (ie, the procedure becomes less efficient; Fig 2). because they must redistribute intravascularly for
For example, an exchange of 1.4 times the EPV decreases removal.
the pretreatment levels of a substance approximately 75%, • Rate of synthesis: Faster synthesis may require more
with minimal additional clearance beyond 1.5 plasma frequent TPE and/or additional therapies to decrease
volumes. In addition, the plasma concentration of the endogenous production.
target substance decreases as a result of dilution by the Most immune complex diseases are related to the pro-
replacement fluid. Thus, TPE sessions typically exchange 1 duction of immunoglobulin G (IgG), a molecule with 45%
volume and virtually never more than 1.5. extravascular distribution, long half-life (22 days), and
The extracorporeal volume, which refers to the volume low turnover per day (7%; Table 3). Therefore, several
of blood outside the body during TPE, should be <15% consecutive treatments each separated by 24-48 hours will
of total blood volume to decrease the risk of be required to achieve meaningful clearance. In general,
complications related to hypovolemia. If necessary, a TPE performed every other day for 6 treatments will
blood prime or transfusion may be required. decrease circulating IgG levels to 16%-20% of the baseline
Number of Exchanges, Duration, and level (Fig 3). Diseases with a high autoantibody produc-
Discontinuation tion rate (eg, anti-GBM disease) require daily sessions with
concomitant immunosuppression.
A 70-kg adult with a hematocrit level of 34% will require
In contrast, IgM is a larger molecule with 80% intra-
approximately 3 L of replacement fluid for a single plasma
vascular distribution, shorter half-life (5 days), and
volume exchange, which will last approximately 1.5-2
higher daily turnover (17%). As such, one TPE will
hours with centrifugation TPE and 3 hours with membrane
achieve sig- nificant clearance, but discontinuation of
filtration TPE. The frequency and number of TPE sessions
therapy will lead to faster rebound than for IgG.
depend on the characteristics of the pathogenic substance
Returning to question 1, option (a), 2.7 L, is the best
and the time required to reach the desired clinical
answer. The estimated plasma volume can be calculated as
improvement. The following factors are important de-
(0.065 × 50 kg) × (1 − 0.18) = 2.7 L. For question 2,
terminants of the efficiency of TPE:
option (d), daily exchange of 1 plasma volume, is the best
• Sieving coefficient: A measure of equilibration of a solute answer. TPE is the first-line therapy for TTP, reducing
across a semipermeable membrane. A sieving coefficient mortality from >90% to 5%-10%. TTP needs to be treated
aggressively

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100 ➢ Stanworth SJ. The evidence-based use of FFP and

Pre
Post cryoprecipitate for abnormalities of coagulation tests
and clinical coagulopathy. Hematology Am Soc Hematol
80
Educ Program. 2007:179-186. https://doi.org/10.1182/
asheducation-2007.1.179 +ESSENTIAL READING
60 ➢ Kaplan AA. Therapeutic plasma exchange: a technical
and operational review. J Clin Apher. 2013;28(1):3-10.
% of initial

40 https://doi.org/10.1002/jca.21257
➢ Neyrinck MM, Vrielink H, Joint Task Force for Education
and Certification. Calculations in apheresis. J Clin Apher.
20
2015;30(1):38-42. https://doi.org/10.1002/jca.21347
+ESSENTIAL READING
0 ➢ ABIM Foundation. American Society for Apheresis.
0 1 2 3 4 5
Day Choosing Wisely | Promoting conversations between
providers and patients. Published April 23, 2018.
Figure 3. Immunoglobulin G removal from 1 plasma volume exchangedAccessed
per dayOctober 7, 2022.
for 3 days. The https://www.choosingwisely.
intertreatment increase is a result of equ
org/societies/american-society-for-apheresis/
➢ Zantek ND, Pagano MB, Rollins-Raval MA, et al. He-
mostasis testing and therapeutic plasma exchange: re-
sults of a practice survey. J Clin Apher. 2019;34(1):26-
32. https://doi.org/10.1002/jca.21666
➢ Staley EM, Hoang ST, Liu H, Pham HP. A brief review
of common mathematical calculations in therapeutic
apheresis. J Clin Apher. 2019;34(5):607-612. https://
doi.org/10.1002/jca.21712 +ESSENTIAL READING
(daily TPE initially) with 1-1.5 plasma volume exchanges.
For question 3, option (a), frozen plasma, is the best
answer. Daily sessions with frozen plasma replacement Indications
Case 2: A 70-year-old man presents with fatigue, dyspnea,
fluid are life- saving, as TPE removes autoantibodies against and hemoptysis. He appears ill, with tachycardia and blood
ADAMTS13 and frozen plasma provides functional pressure 84/55 mm Hg. He is intubated for hypoxemic res-
ADAMTS13. piratory failure. Laboratory testing reveals a hemoglobin
level of 8 g/dL, platelet count of 76 × 103/μL, and Scr
Laboratory Monitoring concen- tration of 3.2 mg/dL (from a baseline of 1.2 mg/dL).
Optimal laboratory testing for hemostasis in patients un- Urinal- ysis reveals microscopic hematuria with 10 %
dergoing TPE is not defined, and there is significant acanthocytes on microscopy. Computed tomography of
practice variation across institutions. The American Society the chest is compatible with DAH. Empirical corticosteroids
for Apheresis (ASFA) and Choosing Wisely do not are initiated, and, based on preliminary results of a
kidney biopsy consistent with anti-GBM disease,
recommend routine monitoring of coagulation tests dur-
cyclophosphamide and TPE are started. Serum antibodies
ing a course of TPE unless the procedure is performed
to myeloperoxidase and proteinase 3 (MPO and PR3) are
daily. This includes TPE performed with nonfrozen plasma not detected, and serum anti-GBM antibody is 52 U (
replacement fluids such as albumin. Red blood cell trans- normal is <1 U).
fusion should be considered to maintain hematocrit
level >22%, and ionized calcium should be measured if
symptoms of hypocalcemia develop. The effect at 48 hours Table 4. Effect of a Single Plasma Volume Exchange on the
of 1 plasma volume exchange on different proteins is Removal and Rebound of Common Blood Constituents Using
shown in Table 4. Albumin and/or Crystalloid Replacement Fluid
Additional important treatment recommendations from DecreaseRebound 48
Choosing Wisely include not placing a central venous Constituent vs Baseline, %h Post Apheresis, %
catheter if peripheral vein access is safe, using frozen Antithrombin III 70 100
plasma replacement fluid only when clearly indicated, and C3 63 60-100
establishing a defined course of apheresis. Factor VIII 50-82 90-100
Fibrinogen 67 46-63
Additional Readings Prothrombin 49 48
➢ Wood L, Jacobs P. The effect of serial therapeutic Immunoglobulins 60 44
plasmapheresis on platelet count, coagulation factors, Liver enzymes 55-60 100
plasma immunoglobulin, and complement levels. J Clin Platelets 25-30 75-100
Values are given as means.
Apher. 1986;3(2):124-128. https://doi.org/10.1002/
jca.2920030209

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Table 5. ASFA Category and Grade Recommendations for Therapeutic Apheresis

Disease Modality Indication Category Grade
Acute disseminated encephalomyelitis TPE Steroid-refractory II 2C
Acute inflammatory demyelinating TPE Primary treatment I 1A
polyradiculoneuropathy (Guillain- IA Primary treatment I 1B
Barre´ syndrome)
Acute liver failure TPE-HV – I 1A
TPE – III 2B
Age-related macular degeneration, dry Rheopheresis High risk II 2B
Amyloidosis, systemic B2M column Dialysis-related amyloidosis II 2B
TPE Other causes IV 2C
Anti-GBM disease (Goodpasture TPE DAH I 1C
syndrome) TPE Not receiving dialysis at presentation I 1B
TPE Receiving dialysis at presentation, III 2B
no DAH
Atopic (neuro-)dermatitis (atopic ECP – III 2A
eczema), recalcitrant IA – III 2C
TPE/DFPP – III 2C
Autoimmune hemolytic anemia, severe TPE Severe cold agglutinin disease II 2C
TPE Severe warm autoimmune III 2C
Babesiosis RBC exchange Severe II 2C
Burn shock resuscitation TPE – III 2B
Cardiac neonatal lupus TPE – III 2C
CAPS TPE – I 2C
Chronic focal TPE – III 2C
encephalitis (Rasmussen
encephalitis)
Chronic inflammatory demyelinating TPE/IA – I 1B
polyradiculoneuropathy
Coagulation factor inhibitors TPE – III 2C
IA – III 2B
Complex regional pain syndrome TPE Chronic III 2C
Cryoglobulinemia TPE Severe/symptomatic II 2A
IA Severe/symptomatic II 2B
Cutaneous T-cell lymphoma; mycosis ECP Erythrodermic I 1B
fungoides; Se´zary syndrome ECP Nonerythrodermic III 2C
Dilated cardiomyopathy, idiopathic IA NYHA II-IV II 1B
TPE NYHA II-IV III 2C
Erythropoietic protoporphyria, liver TPE – III 2C
disease RBC exchange – III 2C
Familial hypercholesterolemia LA Homozygotes I 1A
LA Heterozygotes II 1A
TPE Homozygotes/heterozygotes II 1B
FSGS TPE/IA Recurrent in KTx I 1B
LA Recurrent in KTx/steroid-resistant in II 2C
native kidney
TPE Steroid-resistant in native kidney III 2C
Graft-vs-host disease ECP Acute II 1C
ECP Chronic II 1B
HELLP syndrome TPE Postpartum III 2C
TPE Antepartum IV 2C
Hemophagocytic lymphohistiocytosis; TPE – III 2C
hemophagocytic syndrome;
macrophage activating syndrome
Heparin-induced thrombocytopenia TPE Pre-CPB III 2C
and thrombosis TPE Thrombosis III 2C
Hereditary hemochromatosis Erythrocytapheresis – I 1B
Hyperleukocytosis Leukocytapheresis Symptomatic II 2B
Leukocytapheresis Prophylactic or secondary III 2C
(Continued)

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Table 5 (Cont'd). ASFA Category and Grade Recommendations for Therapeutic

Disease Modality Indication Category Grade
Hypertriglyceridemic pancreatitis TPE/LA Severe III 1C
TPE/LA Prevention of relapse III 2C
Hyperviscosity in TPE Symptomatic I 1B
hypergammaglobulinemia TPE Prophylaxis for rituximab I 1C
IgA nephropathy (Berger disease) TPE Crescentic III 2B
TPE Chronic progressive III 2C
Immune thrombocytopenia TPE/IA Refractory III 2C
Inflammatory bowel disease Adsorptive Ulcerative colitis/Crohn disease III 1B
cytapheresis
ECP Crohn disease III 2C
Lambert-Eaton myasthenic syndrome TPE – II 2C
Lipoprotein(a) hyperlipoproteinemia LA Progressive atherosclerotic CVD II 1B
Malaria RBC exchange Severe III 2B
Multiple sclerosis TPE Acute attack/relapse II 1A
IA Acute attack/relapse II 1B
TPE Chronic III 2B
IA Chronic III 2B
Myasthenia gravis TPE/IA Short-term treatment I 1B
TPE/IA Long-term treatment II 2B
Myeloma cast nephropathy TPE – II 2B
Nephrogenic systemic fibrosis ECP/TPE – III 2C
Neuromyelitis optica spectrum TPE Acute attack/relapse II 1B
disorders IA Acute attack/relapse II 1C
TPE Maintenance III 2C
N-methyl-D-aspartate receptor TPE/IA – I 1C
antibody encephalitis
Overdose, envenomation, and TPE Mushroom poisoning II 2C
poisoning TPE Envenomation III 2C
TPE Drug overdose/poisoning III 2C
Paraneoplastic neurological TPE/IA – III 2C
syndromes
Paraproteinemic demyelinating TPE IgG/IgA/IgM I 1B
neuropathies; chronic acquired TPE Anti-MAG neuropathy III 1C
demyelinating polyneuropathies TPE Multiple myeloma III 2C
TPE Multifocal motor neuropathy IV 1C
PANDAS; Sydenham chorea TPE PANDAS, exacerbation II 1B
TPE Sydenham chorea, severe III 2B
Pemphigus vulgaris TPE Severe III 2B
ECP/IA Severe III 2C
Peripheral vascular diseases LA – II 1B
Phytanic acid storage disease TPE/LA – II 2C
(Refsum disease)
Polycythemia vera; erythrocytosis Erythrocytapheresis Polycythemia vera I 1B
Erythrocytapheresis Secondary erythrocytosis III 1C
Posttransfusion purpura TPE – III 2C
PML associated with natalizumab TPE – III 1C
Pruritus due to hepatobiliary diseases TPE Treatment-resistant III 1C
Psoriasis ECP Disseminated pustular III 2B
Adsorptive Disseminated pustular III 2C
cytapheresis
TPE Disseminated pustular IV 2C
Red cell alloimmunization, prevention RBC exchange Exposure to RhD+ RBCs III 2C
and treatment TPE Pregnancy, GA <20 wk III 2C
Scleroderma (systemic sclerosis) TPE – III 2C
ECP – III 2A
(Continued)

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 Cervantes et

Table 5 (Cont'd). ASFA Category and Grade Recommendations for Therapeutic Apheresis
Disease Modality Indication Category Grade
Sepsis with multiorgan failure TPE – III 2B
Sickle cell disease, acute RBC exchange Acute stroke I 1C
RBC exchange Acute chest syndrome, severe II 1C
RBC exchange Other complications III 2C
Sickle cell disease, nonacute RBC exchange Stroke prophylaxis I 1A
RBC exchange Pregnancy II 2B
RBC exchange Recurrent vaso-occlusive pain crisis II 2B
RBC exchange Preoperative management III 2A
Steroid-responsive encephalopathy TPE – II 2C
associated with autoimmune
thyroiditis (Hashimoto
encephalopathy)
Stiff-person syndrome TPE – III 2C
Sudden sensorineural hearing loss LA/rheopheresis/TPE – III 2A
SLE TPE Severe complications II 2C
Thrombocytosis Thrombocytapheresis Symptomatic II 2C
Thrombocytapheresis Prophylactic or secondary III 2C
TMA, coagulation mediated TPE THBD, DGKE, and PLG gene III 2C
variants
TMA, complement mediated TPE CFH autoantibody I 2C
TPE Complement factor gene variants III 2C
TMA, drug associated TPE Ticlopidine I 2B
TPE Clopidogrel III 2B
TPE Gemcitabine/quinine IV 2C
TMA, infection associated TPE/IA STEC-HUS, severe III 2C
TPE Pediatric HUS III 2C
TMA, TTP TPE – I 1A
TMA, transplant associated TPE – III 2C
Thyroid storm TPE – II 2C
Toxic epidermal necrolysis TPE Refractory III 2B
Transplant, cardiac ECP Cellular/recurrent rejection II 1B
ECP Rejection prophylaxis II 2A
TPE Desensitization II 1C
TPE Antibody-mediated rejection III 2C
Transplant, HSCT, ABOi TPE Major ABOi HPC(M) II 1B
TPE Major ABOi HPC(A) II 2B
RBC exchange Minor ABOi HPC(A) III 2C
TPE Major/minor ABOi with pure RBC III 2C
aplasia
Transplant, HSCT, TPE – III 2C
HLA desensitization
Transplant, liver TPE Desensitization, ABOi living donor I 1C
TPE Desensitization, ABOi deceased III 2C
donor/AMR
ECP Desensitization, ABOi III 2C
ECP Acute rejection/immune suppression III 2B
withdrawal
Transplant, lung ECP Bronchiolitis obliterans syndrome II 1C
TPE AMR/desensitization III 2C
Transplant, kidney, ABO compatible TPE/IA AMR I 1B
TPE/IA Desensitization, living donor I 1B
TPE/IA Desensitization, deceased donor III 2C
Transplant, kidney, ABOi TPE/IA Desensitization, living donor I 1B
TPE/IA AMR II 1B
(Continued)

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Table 5 (Cont'd). ASFA Category and Grade Recommendations for Therapeutic

Disease Modality Indication Category Grade
AAV TPE MPA/GPA/RLV: RPGN, Scr ≥5.7 IIa 1A
mg/dL
TPE MPA/GPA/RLV: RPGN, Scr <5.7 III 2C
mg/dL
TPE MPA/GPA/RLV: DAH I 1C
TPE EGPA III 2C
Vasculitis, IgA (Henoch-Scho€nlein TPE Crescentic RPGN III 2C
purpura) TPE Severe extrarenal manifestations III 2C
Vasculitis, other TPE Hepatitis B polyarteritis nodosa II 2C
TPE Idiopathic polyarteritis nodosa IV 1B
Adsorptive Behcet disease II 1C
cytapheresis
TPE Behcet disease III 2C
VGKC antibody–related diseases TPE/IA – II 1B
Wilson disease, fulminant TPE – I 1C
Abbreviations: AAV, antineutrophil cytoplasmic antibody–associated vasculitis; ABOi, ABO incompatible; AMR, antibody-mediated rejection; ASFA, American Society for
Apheresis; B2M, β2-microglobulin; CAPS, catastrophic antiphospholipid syndrome; CFH, complement factor H; CPB, cardiopulmonary bypass; CVD, cardiovascular
disease; DAH, diffuse alveolar hemorrhage; DFPP, double filtration plasmapheresis; DGKE, diacylglycerol kinase ε; ECP, extracorporeal photopheresis; EGPA, eosino-
philic granulomatosis with polyangiitis; FSGS, focal segmental glomerulosclerosis; GA, gestational age; GBM, glomerular basement membrane; GPA, granulomatosis
with
polyangiitis; HELLP, hemolysis, elevated liver enzymes, and low platelets; HPC, hematopoietic progenitor cell; HSCT, hematopoietic stem cell; HUS, hemolytic uremic
syndrome; IA, immunoadsorption; Ig, immunoglobulin; KTx, kidney transplant; LA, lipoprotein apheresis; MAG, myelin-associated glycoprotein; MPA, microscopic
poly- angiitis; NYHA, New York Heart Association [classification]; PANDAS, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections;
PLG, plasminogen; PML, progressive multifocal leukoencephalopathy; RBC, red blood cell; RhD, rhesus factor D; RLV, renal-limited vasculitis; RPGN, rapidly
progressive
glomerulonephritis; SLE, systemic lupus erythematosus; STEC-HUS, Shiga toxin–producing Escherichia coli hemolytic uremic syndrome; TMA, thrombotic
micro- angiopathy; TPE, therapeutic plasma exchange; TTP, thrombotic thrombocytopenic purpura; THBD, thrombomodulin; VGKC, voltage-gated potassium channel.
Adapted with permission of the copyright holder from Padmanabhan et al, 2019 ( J Clin Apher; https://doi.org/10.1002/jca.21705); original content ©2019 John Wiley and
Sons.
a
Changed to category II from category I in a 2020 update.

Question 4: Which one of the following best describes the Additional Readings
duration of TPE for this patient? ➢ Pham HP, Staley EM, Schwartz J. Therapeutic plasma
(a) Because MPO and PR3 testing gives negative results, exchange-a brief review of indications, urgency,
TPE should be discontinued
schedule, and technical aspects. Transfus Apher Sci.
(b) TPE should be discontinued when serum anti-GBM
antibody is undetectable
2019;58(3):237-246. https://doi.org/10.1016/j.
(c) TPE should be continued for a minimum of 3 sessions transci.2019.04.006
(d) TPE should be continued for a minimum of 10-20 ➢ Padmanabhan A, Connelly-Smith L, Aqui N, et al.
days and until resolution of active organ injury Guidelines on the use of therapeutic apheresis in clin-
ical practice-evidence-based approach from the Writing
For the answer to this question, see the following text. Committee of the American Society for Apheresis: the
eighth special issue. J Clin Apher. 2019;34(3):171-354.
https://doi.org/10.1002/jca.21705 +ESSENTIAL READING
➢ Sanchez AP, Balogun RA. Therapeutic plasma exchange
General Recommendations for TPE in the critically ill patient: technology and indications.
ASFA categorizes and grades 84 diseases and 157 in- Adv Chronic Kidney Dis. 2021;28(1):59-73. https://doi.
dications for therapeutic apheresis. In category I, apheresis org/10.1053/j.ackd.2021.03.005
is first-line therapy. For category II, apheresis is second-
line therapy with efficacy favored by available evidence
but conventional therapy should be tried first. For category Nephrology-Specific Indications for TPE Autoantibodies
III, the role of apheresis has not been established, so the are frequently associated with primary kidney diseases
decision needs to be individualized. In category IV, the and are ideal candidates for TPE. Nevertheless, few
evidence suggests that apheresis is ineffective or harmful. kidney diseases have evidence to support the use of
In terms of ASFA grading, grade 1 is a strong recom- TPE, and, in the 2021 KDIGO glomerular diseases
mendation, whereas grade 2 is weak. Quality of evidence is guideline, the only recommenda- tion for TPE is for
indicated by the letters A, B, and C, which represent anti-GBM disease (KDIGO grade 1C). Other conditions
high- quality, moderate-quality, and low-quality in which TPE may be beneficial are presented as
evidence, respectively (Table 5). These guidelines are practice points. The category I renal in- dications
updated approximately every 3 years, with the most recent based on the ASFA guidelines are reviewed in the
version dated 2019. following sections.

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 Cervantes et

Anti-GBM Disease brain, heart, and skin, although large vessels can also be
Anti-GBM disease (ie, Goodpasture syndrome) is an involved. Approximately 65% of episodes have a precipi-
autoimmune disorder in which IgG antibodies directed tating event.
against the α3 chain of type IV collagen result in glomer- The current ASFA recommendations are based on 5 case
ulonephritis and/or alveolar hemorrhage. Often a rapidly series involving 192 patients, and are as follows:
progressive glomerulonephritis, kidney failure develops in • Management: Anticoagulation, steroids, and TPE and/or
approximately 55% of patients despite treatment. IV immunoglobulin
A single randomized controlled trial (RCT) of 17 pa- • TPE prescription:
tients showed favorable kidney outcomes and improved ○ Plasma volume: 1-1.5 EPV
survival with TPE. In 2001, it was reported that patients
○ Frequency: Daily or every other day
receiving dialysis at presentation with 100% crescents on
○ Replacement fluid: Frozen plasma or frozen plasma/
biopsy did not experience recovery of kidney function.
albumin
In 2018, a retrospective analysis of 123 patients
○ Duration: Minimum of 3 to 5 sessions with longer-
confirmed these findings and further determined that
those with ≥50% global glomerulosclerosis had adverse term duration based on clinical response
kidney outcomes. Therefore, the KDIGO glomerular
diseases guideline recommends TPE except in patients who Additional Readings
require dialysis with (1) 100% crescents or (2) >50% ➢ Rodr´ıguez-Pinto´ I, Moitinho M, Santacreu I, et
global glomerulosclerosis and no pulmonary al. Catastrophic antiphospholipid syndrome (CAPS):
hemorrhage. descriptive analysis of 500 patients from the Interna-
The current ASFA recommendations are as follows: tional CAPS Registry. Autoimmun Rev. 2016;15(12):1120-
• Management: Therapy with corticosteroids, cyclophos- 1124. https://doi.org/10.1016/j.autrev.2016.09.010
phamide, and TPE ➢ Legault K, Schunemann H, Hillis C, et al. McMaster
• TPE prescription: RARE- Best practices clinical practice guideline on
○ Plasma volume: 1-1.5 EPV diagnosis and management of the catastrophic
○ Frequency: Daily antiphospholipid syn- drome. J Thromb Haemost.
○ Replacement fluid: Albumin or frozen plasma if DAH is Published online June 7, 2018.
present https://doi.org/10.1111/jth.14192
○ Duration: Minimum of 10-20 days and until
resolution of active glomerular and/or pulmonary Focal Segmental Glomerulosclerosis Following
injury; some providers continue until antibody Kidney Transplant
testing is negative, although the necessity of this
The etiology of this primary podocytopathy remains un-
approach has not been established with certainty; if
known, but a circulating factor has been postulated.
seronegative disease at presentation, minimum of 10-
Recently, anti-nephrin antibodies have been implicated in
20 days and until reso- lution of active organ injury
the pathogenesis and may represent a target of TPE in this
Returning to question 4, the best answer is (d), TPE disorder for some patients. After transplant, the risks of
should be continued for a minimum of 10-20 days and non-postadaptive recurrence of focal segmental glomer-
until resolution of active organ injury. ulosclerosis (FSGS) are generally 20%-50% in the first
allograft and 80%-100% in subsequent allografts. Despite
Additional Readings treatment, 30%-60% of patients experience progression to
➢ Levy JB, Turner AN, Rees AJ, Pusey CD. Long-term kidney failure within 3-7 years. FSGS may recur a few
outcome of anti-glomerular basement membrane anti- hours to 2 years after transplant.
body disease treated with plasma exchange and immu- The current ASFA recommendations, based on 50 case
nosuppression. Ann Intern Med. 2001;134(11):1033- series involving 628 patients and 4 controlled trials, are as
1042. https://doi.org/10.7326/0003-4819-134-11- follows:
200106050-00009 +ESSENTIAL READING • Management: Steroids, rituximab, and TPE and/or IV
➢ van Daalen EE, Jennette JC, McAdoo SP, et al. Predicting immunoglobulin
outcome in patients with anti-GBM glomerulone- • TPE prescription:
phritis. Clin J Am Soc Nephrol. 2018;13(1):63-72. ○ TPE, lipoprotein apheresis, or immunoadsorption with
https://doi.org/10.2215/CJN.04290417 regenerative adsorbers can be used; for TPE, plasma
volume of 1-1.5 EPV
○ Frequency: Daily or every other day
Catastrophic Antiphospholipid Syndrome
○ Replacement fluid: Albumin
Catastrophic antiphospholipid syndrome (CAPS) is defined
○ Duration: Three daily TPEs followed by 6 more ses-
by the presence of antiphospholipid antibodies and mul-
sions in the following 2 weeks; for lipoprotein
tiple thromboses in at least 3 organ systems in less than 1
apheresis, 2 sessions per week for 3 weeks followed by
week. It typically affects small vessels of the kidneys, lungs,
6 weekly treatments

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Additional Readings Current ASFA recommendations, based on 5 case series

➢ Kashgary A, Sontrop JM, Li L, et al. The role of plasma with a total of 174 patients, are as follows:
exchange in treating post-transplant focal segmental • Management: Drug discontinuation plus TPE
glomerulosclerosis: a systematic review and meta- • TPE prescription:
analysis of 77 case-reports and case-series. BMC Neph-
○ Plasma volume: 1-1.5 EPV
rol. 2016;17(1):104. https://doi.org/10.1186/
○ Frequency: Daily or every other day
s12882-016-0322-7
○ Replacement fluid: Frozen plasma
➢ Raina R, Wang J, Sharma A, Chakraborty R. Extracor-
○ Duration: Daily until recovery of hematologic param-
poreal therapies in the treatment of focal segmental
eters (similar to immune TTP)
glomerulosclerosis. Blood Purif. 2020;49(5):513-523.
https://doi.org/10.1159/000506277 +ESSENTIAL READING
Thrombotic Microangiopathy: TTP
Thrombotic Microangiopathy: Factor H TTP is a systemic thrombotic illness of small vessels that
Autoantibody–Mediated has a 90% mortality rate if untreated. Clinical characteris-
Activation of the alternative pathway of complement is a tics include thrombocytopenia and microangiopathic he-
cause of thrombotic microangiopathy (TMA). Genetic var- molytic anemia (MAHA) in combination with deficiency
iants in the alternative pathway are present in of plasma ADAMTS13 activity (<10%). Because the activity
approximately 60% of patients, and an autoantibody assay may not be readily available, the PLASMIC score may
inhibiting comple- ment factor H function is present in help triage patients for TPE who are at high risk for
<10%. ADAMTS13 deficiency. In most patients, IgG autoanti-
TPE in combination with immunosuppression can be an bodies against ADAMTS13 are present. TPE aims to remove
effective therapy, as is treatment with a complement C5 anti-ADAMTS13 antibodies while replacing ADAMTS13
antagonist. The current ASFA recommendations, based on 5 activity through frozen plasma.
case series involving a total of 126 patients, are as follows: Current ASFA recommendations, based on 7 RCTs
involving 301 patients and 5 clinical trials with 270 pa-
• Management: TPE and/or eculizumab with
immunosuppression tients, are as follows:
• TPE prescription: • Management: Steroids and TPE; adjunct therapies can be
○ Plasma volume: 1-1.5 EPV
used in refractory cases; if rituximab is used, a 24-hour
○ Frequency: Daily
interval should be allowed between infusion and TPE;
○ Replacement fluid: Frozen plasma or frozen plasma/
caplacizumab (a monoclonal antibody against von Wil-
albumin lebrand factor) is also available
• TPE prescription:
○ Duration: Until adequate clinical response or antibody
○ Plasma volume: 1-1.5 EPV
titer reduced to less than clinical threshold (similar
○ Frequency: Daily
to immune TTP)
○ Replacement fluid: Frozen plasma
3
Additional Readings ○ Duration: Daily until platelet count is >150 × 10 /μL

➢ Sinha A, Gulati A, Saini S, et al. Prompt plasma ex- and lactate dehydrogenase level is near normal for 2-3
changes and immunosuppressive treatment improves consecutive days
the outcomes of anti-factor H autoantibody-associated
hemolytic uremic syndrome in children. Kidney Int. Additional Readings
2014;85(5):1151-1160. https://doi.org/10.1038/ ➢ Sarode R, Bandarenko N, Brecher ME, et al. Thrombotic
ki.2013.373 +ESSENTIAL READING thrombocytopenic purpura: 2012 American Society for
➢ Iorember F, Nayak A. Deficiency of CFHR plasma Apheresis (ASFA) consensus conference on classifica-
proteins and autoantibody positive hemolytic uremic tion, diagnosis, management, and future research. J Clin
syndrome: treatment rationale, outcomes, and Apher. 2014;29(3):148-167. https://doi.org/10.1
monitoring. Pediatr Nephrol. 2021;36(6):1365-1375. 002/jca.21302
https://doi.org/10.1 007/s00467-020-04652-x ➢ Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and
external validation of the PLASMIC score for rapid
assessment of adults with thrombotic micro-
Thrombotic Microangiopathy: Ticlopidine-
angiopathies: a cohort study. Lancet Haematol.
Associated
2017;4(4):e157-e164. https://doi.org/10.1016/
Drug-induced TMA has been associated with numerous S2352-3026(17)30026-1 +ESSENTIAL READING
drugs, including but not limited to ticlopidine, ➢ Zheng XL, Vesely SK, Cataland SR, et al. ISTH guide-
calcineurin inhibitors, and gemcitabine. Ticlopidine lines for treatment of thrombotic thrombocytopenic
usually presents with severely diminished ADAMTS13 purpura. J Thromb Haemost. 2020;18(10):2496-2502.
levels (<10%) within 2 weeks of drug exposure, often https://doi.org/10.1111/jth.15010 +ESSENTIAL READING
with an autoan- tibody directed against ADAMTS13.

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Living-Donor ABO-Compatible Kidney Transplant, ABO-incompatible kidney transplants. In living-donor

Antibody-Mediated Rejection or Desensitization kidney transplants, A2 donors are preferred over A1
Antibodies to donor HLA and non-HLA antigens may because the risk for rejection is lower as a result of
preclude living-donor transplant and result in antibody- reduced expression of the A antigen on red blood cells
mediated rejection (AMR) after transplant. To permit and endothelium.
successful transplant via desensitization, conditioning Current ASFA recommendations, based on 26 case series
regimens that include TPE may reduce circulating donor- involving 911 patients, are as follows:
specific antibodies to a level insufficient for cytotoxicity. • Management: TPE, immunoadsorption
Similarly, TPE is important in the management of acute • TPE prescription:
AMR after transplant. Although TPE is a mainstay of ○ Plasma volume: 1-1.5 EPV
AMR management, the optimal therapeutic approach ○ Frequency: Daily or every other day
remains unknown. The current ASFA recommendations
○ Replacement fluid: Albumin or frozen plasma
are based on three RCTs involving 61 patients and 8
(should be compatible with recipient and donor ABO
clinical trials with 342 patients (for desensitization from type); frozen plasma is used before and after
living donors, TPE is guided by 6 clinical trials [583 surgery
patients]) and are as follows:
○ Duration: Until cross-match is less than institution-
• Management: AMR can be treated with TPE, double dependent thresholds before transplant
filtration plasmapheresis, and immunoadsorption, always
in conjunction with other immunosuppressive drugs;
Vasculitis, Antineutrophil Cytoplasmic Antibody–
desensitization regimens include IV immunoglobulin,
Associated
rituximab, and optional additional immunosuppression
Antineutrophil cytoplasmic antibody (ANCA)–associ-
• TPE prescription:
ated vasculitis (AAV) is a necrotizing small-vessel
○ Plasma volume: 1-1.5 EPV
vasculitis in which few or no immune deposits are
○ Frequency: Daily or every other day
apparent in kidney biopsy specimens. The kidneys are
○ Replacement fluid: Albumin or frozen plasma plus IV
involved in 70% of cases and the lungs in >50%. The
immunoglobulin 100-200 mg/kg most common kidney manifestation is rapidly pro-
○ Duration: For AMR, TPE is usually daily or every
gressive glomerulonephritis, and lung involvement can
other day for 5 or 6 sessions or based on clinical range from asymptomatic pulmonary lesions to life-
outcomes and decrease in donor-specific antibody threatening DAH. In its clinical presentation, the
titers; for those receiving TPE for desensitization, pulmonary-renal syndrome associated with ANCA may
TPE is performed until cross-match is less than have similarities to anti-GBM disease. In cases in which
institution-dependent thresholds or postoperatively ANCA and anti-GBM are present, the initial therapy
for a minimum of 3 procedures should follow guidelines for management of anti-GBM
disease. An induction regimen with steroids and
Additional Readings cyclophosphamide or rituximab leads to remission in as
➢ Wan SS, Ying TD, Wyburn K, Roberts DM, Wyld M, many as 90% at 6 months. Maintenance therapy
Chadban SJ. The treatment of antibody-mediated can include rituximab, azathioprine, or mycophenolate
rejection in kidney transplantation: an updated sys- mofetil, sometimes in combination with low-dose
tematic review and meta-analysis. Transplantation. steroids.
2018;102(4):557-568. https://doi.org/10.1097/TP. In 2007, results were reported from the MEPEX trial of
0000000000002049 +ESSENTIAL READING 137 patients with AAV randomized to receive standard care
➢ Simmons SC, Adamski J, Berg M, et al. The apheresis (oral steroids and cyclophosphamide) plus IV methylpred-
management of patients undergoing transplantation: a nisolone or TPE. MEPEX enrolled patients with severe kid-
concise review. Transfusion. 2019;59(5):1863-1869. ney injury based on Scr concentration >5.8 mg/dL or
https://doi.org/10.1111/trf.15153 dialysis treatment. In patients receiving TPE, there were
22% and 24% lower risks of kidney failure at 3 and 12
months, respectively. In 2020, the PEXIVAS trial
Living Donor ABO-Incompatible
randomized 704 patients with an estimated
Kidney Transplant, Desensitization
glomerular filtration rate <50 mL/min/1.73 m2 or
If untreated, ABO-incompatible kidney transplants are at pulmonary hemorrhage to receive 0 or 7 sessions of TPE
risk of hyperacute and acute AMR. The use of TPE in the in combination with induc- tion pulse
peritransplant period has been proven to decrease anti-A methylprednisolone and cyclophosphamide or rituximab.
and/or anti-B titers and facilitate graft survival. Short-
The median Scr concentration was 3.8 mg/dL, 20% were
and long-term outcomes are similar in ABO-
receiving dialysis, and 41% had pulmonary involvement.
incompatible and ABO-compatible transplants, although
There was no difference in the primary outcome by 12
BK virus–associated nephropathy is a greater risk in months. In subgroup analysis, however, TPE appeared
favorable in those with pulmonary hemorrhage or severe
kidney disease (Scr >5.7 mg/dL), although this was

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Table 6. Characteristics of Common Drugs Removed by TPE

➢ Balogun RA, Sanchez AP, Klingel R, et al. Update to
Protein Volume of the ASFA guidelines on the use of therapeutic
Drug Binding, % Distribution, L/kg apheresis in ANCA-associated vasculitis. J Clin Apher.
Acetaminophen <3 0.1 2020;35(5):493- 499.
Acetylsalicylic acida 80-90 0.1-0.2 https://doi.org/10.1002/jca.21820
Azathioprine 30 0.6
Cefazolina 80 0.13-0.22
Ceftriaxonea 90 0.12-0.18 Special Considerations
Cyclosporine 90-98 13
Cyclophosphamide 23 0.8 Concomitant Use of Angiotensin-Converting Enzyme
Digoxin 20-30 5-8 Inhibitors
Eculizumab NA 5-8 Because angiotensin-converting enzyme inhibitors block
Glyburidea 99 0.16-0.3 the degradation of bradykinins, hypotension can occur if
Heparina >90 0.06-0.1 kinins are activated during apheresis in patients taking
Ibuprofena 99 0.15-0.17 these medications. This was reported most commonly with
Levothyroxinea 90 0.1-0.2 the use of hydrophilic, electronegative membranes such as
Prednisone-prednisolone 90-95 0.6-0.7 the polyacrylonitrile AN69 filter. Dextran sulfate systems,
Rituximab NA 3.1-4.5 albumin replacement fluids, and the Plasmaflo OP filter
Valproic acida 90 0.19-0.23 (polyethylene) have also been linked to this reaction. Many
Tobramycin 10 0.25 practitioners continue to hold angiotensin-converting
Vancomycin 70 0.39
enzyme inhibitors 24-48 hours before TPE, particularly
Verapamila 90 NA
if albumin replacement or membrane filtration TPE is used.
Warfarina 97-99 0.11-0.15
Abbreviations: NA, not applicable; TPE, therapeutic plasma exchange.
Based on information in Ibrahim & Balogun, 2012 (Semin Dial; https://doi.org/1 Drug Removal
0.1111/j.1525-139x.2011.01030.x) and Mahmoud et al, 2021 (Neurocrit Care;
https://doi.org/10.1007/s12028-020-00989-1).
Plasma exchange may affect drug concentrations through
a
Drugs that are particularly amenable to removal by TPE. direct removal or via removal of metabolizing enzymes.
This is important for drug dosing and determining
whether extracorporeal therapy can be beneficial in treat-
not statistically significant. In 2020, the ASFA guidelines ing intoxications. In general, all daily drug dosing should
were updated to maintain the category I indication for be administered after the TPE session. TPE is most likely to
DAH, even though Scr concentration ≥5.7 mg/dL or dialysis remove drugs with a very low volume of distribution
was changed to category II. The current ASFA (<0.2 L/kg) and high protein binding (>80%). Glyburide
recommendations are based on 10 RCTs involving 1,091 intoxication, for example, would be more amenable to
patients and 5 clinical trials with 345 patients (before the treatment with TPE than cyclosporine (Table 6).
publication of PEXIVAS) and are as follows: Specific immunosuppressants are worth discussing in
• Management: Induction with pulsed methylprednisolone more detail. Prednisone is converted to prednisolone,
and rituximab or cyclophosphamide with or without TPE which is highly protein-bound with a moderately low
• TPE prescription: volume of distribution. TPE removes only 1% of prednis-
○ Plasma volume: 1-1.5 EPV olone, and additional doses are not required after TPE.
○ Frequency: Daily or every other day Cyclosporine and tacrolimus are predominantly intracel-
○ Replacement fluid: Albumin or frozen plasma if DAH lular and not affected by plasma exchange. Cyclophos-
present phamide is unlikely to be removed by TPE. Rituximab
○ Duration: Seven sessions over a median period of 14 has limited data, although 47%-54% may be removed
days (as many as 12 sessions have been reported) when TPE is performed 24-72 hours after administration.
Most of the effect occurs in 12-24 hours, so a dose can
be administered after a TPE session with delay of the
Additional Readings next session for 24-48 hours.
➢ Jayne DR, Gaskin G, Rasmussen N, et al. Randomized There are limited data on the effect of TPE on many old
trial of plasma exchange or high-dosage and new drugs. Factors such as endogenous clearance and
methylprednisolone as adjunctive therapy for severe extravascular distribution influence their clearance with
renal vasculitis. J Am Soc Nephrol. 2007;18(7):2180- TPE but may not be widely available. According to some
2188. https://doi.org/1 0.1681/ASN.2007010090 studies, additional doses of aspirin, phenytoin, proprano-
➢ Walsh M, Merkel PA, Peh CA, et al. Plasma exchange lol, and thyroxine may be needed after TPE.
and glucocorticoids in severe anca-associated vasculitis.
N Engl J Med. 2020;382(7):622-631. https://doi.org/1
0.1056/NEJMoa1803537 +ESSENTIAL READING Additional Readings
➢ Ibrahim RB, Balogun RA. Medications in patients treated
with therapeutic plasma exchange: prescription dosage,

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timing, and drug overdose. Semin Dial. 2012;25(2):176- symptoms abate and there is cessation of delayed toxin
189. https://doi.org/10.1111/j.1525-139X.2011.01 release from tissues.
030.x For question 5, option (c), protein binding of 90%,
➢ Puisset F, White-Koning M, Kamar N, et al. is the best answer. The volume of distribution of lev-
Population pharmacokinetics of rituximab with or othyroxine is 0.1-0.2 L/kg, with 90% protein-bound
without plas- mapheresis in kidney patients with (Table 6), both of which are favorable characteristics
antibody-mediated disease. Br J Clin Pharmacol. for removal by TPE.
2013;76(5):734-740.
https://doi.org/10.1111/bcp.12098
➢ Mahmoud SH, Buhler J, Chu E, Chen SA, Human T. Additional Reading
Drug dosing in patients undergoing therapeutic plasma ➢ King JD, Kern MH, Jaar BG. Extracorporeal removal of
exchange. Neurocrit Care. 2021;34(1):301-311. https:// poisons and toxins. Clin J Am Soc Nephrol.
doi.org/10.1007/s12028-020-00989-1 +ESSENTIAL 2019;14(9):1408-1415. https://doi.org/10.2215/
READING CJN.02560319 +ESSENTIAL READING

Intoxications Simultaneous Extracorporeal Therapies

Case 3: A 50-kg 35-year-old man with history of Patients who require TPE may also need other extracor-
hypothy- roidism is found unresponsive. In the emergency poreal therapies such as kidney replacement therapy or
department, he is diaphoretic and lethargic with a ECMO. When the procedures are continuous, they can be
temperature of 101 ◦F, rapid atrial fibrillation with heart rate performed independently through separate vascular ac-
of 170 beats/min, and blood pressure 94/60 mm Hg. He is cesses or in parallel through the same access. Potential
given lactated Ringer limitations of the latter approach include access pressure
solution, IV amiodarone, and IV metoprolol. The patient ex- alarms, circuit clotting, and risk for air embolism.
periences cardiac arrest with return of spontaneous In patients receiving intermittent hemodialysis for
circula- tion after 2 rounds of cardiopulmonary resuscitation.
kidney failure, alkalemia may result from repeated
Bedside echocardiogram shows severe global dysfunction.
Hemato- crit level is 38%, and thyroid function tests
apheresis treatments when frozen plasma is the pri-
reveal an unde- tectable thyroid-stimulating hormone level, mary replacement fluid. Therefore, if TPE and dialysis
free thyroxine level >60 ng/dL (reference range, 0.8-1.8 are required on the same day, TPE should be per-
ng/dL), and free triiodothyronine level >50 pg/mL (reference formed first to allow subsequent dialysis to correct the
range, 2-4.9 pg/ mL). Emergent TPE is planned to treat blood pH or hypervolemia resulting from TPE.
thyroid storm with cardiogenic shock thought to have Importantly, TPE should not be used as an ultrafiltra-
resulted from levothyr- oxine intoxication. tion procedure by intentionally replacing less than the
exchanged volume.
Question 5: Which one of the following characteristics of In ECMO, inflow to the TPE circuit can originate
levothyroxine make it amenable to removal by TPE? before or after the oxygenator. Plasma, heparin, and
(a) Volume of distribution >1 L/kg calcium gluconate infusions may be attached to this port
(b) Large intracellular concentration via a stopcock. Return from the TPE circuit connects before
(c) Protein binding of 90%
the oxygenator to prevent air embolism. If the returning
(d) Slow release from tissue
blood enters before the centrifugal pump, resistance tubing
For the answer to the question, see the following text. may be needed to maintain adequate return pressures.
Because the ECMO circuit is anticoagulated with heparin,
In addition to low volume of distribution (<0.2 L/ citrate is not used, and frozen plasma is the preferred
kg) and high protein binding (>80%), the time between replacement fluid. High circuit pressures may be a
drug/toxin administration and TPE initiation determines limitation, and lower ECMO blood flow rates can help run
removal by apheresis. Routinely, albumin is used as the both circuits simultaneously.
replacement fluid to facilitate binding and trapping of
the substance in the blood compartment for elimination. Additional Readings
However, there are some substances that may prefer- ➢ Laverdure F, Masson L, Tachon G, Guihaire J, Stephan
entially bind to plasma proteins other than albumin.
F. Connection of a renal replacement therapy or plas-
Examples include dipyridamole, quinidine, imipramine, mapheresis device to the ECMO circuit. ASAIO J.
propranolol, and chlorpromazine, which have strong 2018;64(1):122-125. https://doi.org/10.1097/MAT.
affinities for α-1-acid glycoprotein. Some venoms 0000000000000621
may cause coagulopathy and microangiopathy, and ➢ Manuel L, Fong LS, Lahanas A, Grant P. How to do
frozen plasma can restore ADAMTS13 and coagulation it: Plasmapheresis via venoarterial extracorporeal
factors. In these examples, frozen plasma is preferred.
TPE of 1-2 plasma volumes daily continues until clinical

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Table 7. Complications Associated With TPE

Complication Mechanism Frequency
Access-related
Peripheral access Hematomas, nerve damage, sclerosis of 1.48%
veins/ arteries
CVC Thrombosis, infections, pneumothorax, arterial 0.11%-0.36% (more
puncture, air embolism complications in subclavian
[60%] vs jugular [20%] CVCs)
Ports Early: pneumothorax, hematomas, arrhythmia, 18%
arterial puncture; late: thrombosis, port-pocket
infection, pinch-off syndrome
AVF/AVG Thrombosis 12%-20%
Inadequate maturation 60%
Anticoagulation-related
Hypomagnesemia Citrate chelation NA
Thrombocytopenia Heparin-induced thrombocytopenia 1%-5% (not specific to TPE)
Procedure-related
Anemia Hematocrit may decrease 10% due to NA
intravascular expansion with hyperoncotic
fluids; hemolysis if hypo-oncotic priming
solutions used
Hypotension, dyspnea, Complement-mediated membrane 0.4%-15%
chest pain bioincompatibility; ethylene oxide
hypersensitivity
Thrombocytopenia Loss of platelets in the discarded plasma, circuit NA
clotting, or dilutional effect by replacement fluid
Vitamin deficiencies Depletion of protein-bound vitamins (A, B6, B12, NA
C, and E and β-carotene) of 24%-48% with
rebound to pretreatment levels within 24 h
Replacement fluid–related
Anaphylactoid reactions Transfusion of IgA in donor plasma to patients 0.02%-0.07%
with selective IgA deficiency; contamination
with bacteria, endotoxins, pyrogens; presence
of prekallikrein activator and bradykinin (ACEI);
antibodies to polymerized albumin (rare)
Coagulopathy Depletion of coagulation factors and its 0.06%-0.14% for thrombosis,
inhibitors related to albumin replacement alone 0.06% for bleeding
(Table 4)
Electrolyte/acid base Hypokalemia (albumin), hypocalcemia (frozen 9%-19.6% for hypocalcemia,
abnormalities plasma), hypomagnesemia (frozen plasma), 0.03% for alkalosis
metabolic alkalosis (frozen plasma)
Infection Hypogammaglobulinemia (albumin), viral NA
transmission (frozen plasma)
Transfusion-related Transfusion of donor antibodies (frozen plasma) NA
lung injury
Hypervolemia Administration of replacement fluid NA
Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; AVF, arteriovenous fistula; AVG, arteriovenous graft; CVC, central venous catheter; IgA, immunoglobulin A;
NA, not applicable; TPE, therapeutic plasma exchange.

membrane oxygenation circuit for thyroid storm. Ann

Med Surg (Lond). 2021;67:102485. https://doi.org/10.1 an increase in urinary protein-creatinine ratio (from 0.2 to
016/j.amsu.2021.102485 3.9 g/g) with worsening allograft function. You suspect
recurrence of FSGS and initiate membrane filtration TPE
with a Prismaflex TPE-2000 filter and frozen plasma
replacement while awaiting results of allograft biopsy.
Complications
Question 6: Eighty minutes into her TPE session, the patient
Case 4: A 22-year-old woman with kidney failure caused by reports muscle cramps and paresthesia. Which one of the
primary FSGS is seen 3 days after deceased-donor following is the most likely cause of her symptoms?
kidney transplant. She has persistent sanguineous drainage a. Citrate-induced electrolyte abnormalities
from Jackson-Pratt drains. Immunosuppression includes b. Bradykinin generation caused by interaction of tacrolimus
tacroli- mus twice daily, mycophenolate mofetil 1,000 mg with the filter
twice daily, and prednisone 10 mg/d. Laboratory testing
demonstrates

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 Cervantes et

c. Ethylene oxide hypersensitivity Additional Readings

d. IgA-induced anaphylactoid reaction ➢ Kaplan A. Complications of apheresis. Semin Dial.
2012;25(2):152-158. https://doi.org/10.1111/
For the answer to the question, see the following text. j.1525-139X.2011.01026.x +ESSENTIAL READING
➢ Lemaire A, Parquet N, Galicier L, et al. Plasma exchange
in the intensive care unit: Technical aspects and com-
TPE is generally a safe procedure, but the practitioner plications. J Clin Apher. 2017;32(6):405-412. https://
must be vigilant for numerous potential complications doi.org/10.1002/jca.21529 +ESSENTIAL READING
(Table 7). Hypocalcemia is the most common ➢ Coirier V, Lesouhaitier M, Reizine F, et al. Tolerance
complication and is more frequent with frozen plasma and complications of therapeutic plasma exchange by
(20%) than albu- min (9%). Patients with reduced renal or centrifugation: a single center experience. J Clin Apher.
liver excretion of citrate are more susceptible to the 2022;37(1):54-64. https://doi.org/10.1002/jca.21
development of citrate toxicity. Different interventions 950
such as the addition of IV calcium to albumin bottles,
slowing the citrate infusion, or using ACD-B have been
Article Information
reported, but most practices provide intermittent IV
calcium or a continuous IV calcium infusion with the Authors’ Full Names and Academic Degrees: C. Elena
returning blood. Hypokalemia can result from the Cervantes, MD, Evan M. Bloch, MBChB, MS, and C. John
Sperati, MD, MHS.
approximately 25% reduction in blood potassium concen-
Authors’ Affiliations: Division of Nephrology, Department of
tration seen with albumin replacement. Similar to calcium, Medicine (CEC, CJS), and Division of Transfusion
the addition of potassium to the albumin bottle can be Medicine, Department of Pathology (EMB), Johns Hopkins
helpful in preventing this. Hypotension has been reported University School
in of Medicine, Baltimore, MD.
0.4%-15% of treatments and is more common with com- Address for Correspondence: C. John Sperati, MD, MHS, 1830 E
Monument St, Room 416, Baltimore, MD 21287. Email:
bination albumin–saline solution replacement. Potential jsperati@ jhmi.edu
mechanisms include delayed or inadequate volume replace- Support: None.
ment, vasovagal episodes, low oncotic fluid replacement,
Financial Disclosure: Dr Sperati reports membership in the
anaphylaxis, transfusion-associated lung injury, arrhythmia, American Board of Internal Medicine (ABIM) Nephrology
bradykinin reactions, bleeding from vascular access, and Longitudinal Knowledge Assessment Approval Committee and
cardiovascular collapse. If an 80:20 ratio of albumin to receipt of honoraria from Alexion Pharmaceuticals for serving on
saline solution is used, one approach to minimize data safety monitoring boards. Dr Bloch reports personal fees and
hypotension is to replace at 110% of the volume exchanged. nonfinancial support from Terumo BCT and Abbott Laboratories
The mortality rate associated with apheresis is low, outside of the submitted work and membership in the US Food
and Drug Administration (FDA) Blood Products Advisory
ranging from 0.03% to Committee. Dr Cervantes declares that she has no relevant
0.05%, and is primarily related to the underlying disease(s). financial interests.
For question 6, answer (a), citrate-induced electrolyte Disclaimer: No ABIM examination questions are shared or
abnormalities, is the best answer. Frozen plasma is 14% otherwise disclosed in this article. Any views or opinions that
citrate, and the risk for citrate-induced hypocalcemia and are expressed in this manuscript are those of the authors,
based on their own scientific expertise and professional
hypomagnesemia is higher in membrane filtration TPE
judgment; they do not necessarily represent the views of either
than in centrifugation TPE. Bradykinin generation was the Blood Products Advisory Committee or the formal position
most common with older polyacrylonitrile membranes in of the FDA, and also do not bind or otherwise obligate or
the setting of angiotensin-converting enzyme inhibitor use commit either Advisory Committee or the Agency to the views
(not tacrolimus), although some albumin lots can also expressed.
have increased concentrations of prekallikrein-activating Peer Review: Received August 10, 2022, in response to an
factor activity. Ethylene oxide from membrane steriliza- invitation from the journal. Evaluated by 3 external peer reviewers
tion or transfusion of IgA present in frozen plasma into and a member of the Feature Advisory Board, with direct editorial
input from the Feature Editor and a Deputy Editor. Accepted in
patients with selective IgA deficiency can result in revised form October 19, 2022.
anaphylactoid reactions. Paresthesia, however, is more
commonly a result of hypocalcemia.

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