ANTICOAGULANTS IN THE PICU

A PRACTICAL GUIDE

MOHAMED KHALED
PICU INTENSIVIST
Aswan Heart Centre
Classic coagulation cascade
Coagulation cascade
REVISED VERSION
Cell based model

4 phases :

1. Initiation
2. Amplification
3. Propagation
4. Termination
Basics
1. Most of coagulation factors are made in the liver
2. Factors II,VII,IX,X undergo enzymatic transformation in the liver , only with the
help of vitamin K (4 of 12 coagulation factors)
3. Warfarin prevent this enzymatic transformation
4. Children under 6 months of age have decreased levels of factors (II, VII, IX, X, XI,
and XII) , levels of (protein C, protein S, and AT)
5. Protein C & S , Tissue factor pathway inhibitor (TFPI) , Antithrombin (AT) , are
natural coagulants … protein C&S are vitamin K dependent
Anticoagulant medications

1. Antiplatelets : Aspirin, Clopidogrel, Dipyridamol

2. Unfractionated Heparin
3. Low Molecular Weight Heparin : Enoxaparin
4. Fondaparinox
5. Vitamin K antagonists (VKA) : Warfarin
6. Direct Oral Anticoagulants DOACs (NOACs)
 1. Mechanism of action : prevent
platelet aggregation through
inhibition of COX 1 (no
Antiplatelets Thromboxane A2 production)
2. Dose : oral , anti platelet 5
mg/kg OD , anti inflammatory
10 mg/kg QDS
3. 2 doses should be
administered before stopping
heparin
Aspirin 4. If patient is sensitive to or has
viral infection can be safely
shifted to dipyridamole
 1. Mechanism of action : irreversible
inhibition of platelet activation and
aggregation
2. Dose : Oral (limited data available )

<24 months old : 0.2 mg/kg/dose

Antiplatelets OD

>2 years : 1mg/dose OD

3. Combined with aspirin in PDA

stent patients
4. Give PPI , avoid omeprazole
5. Contraindicated in severe hepatic
Clopidogrel impairment
Plavix 6. In non cardiac brain stroke patients
may increase the dose to 1
mg/kg/dose
Antiplatelets 1. Mechanism of action :
Inhibition of Thromboxane A2
formation
2. Dose : Oral (off - label use )

3-6 mg/kg/day divided Q8hrs

Dipyridamol
 1. Mechanism of action :
inactivates factor Xa by
binding to antithrombin (AT)
Unfractionated heparin 2. Onset of action : IV :
Immediate
3. Monitoring : aPTT,ACT, anti
factor Xa activity
4. Target aPTT of 1.5 to 2.5
times the mean of the
control value
Heparin 5. Antidote : Protamine sulfate
 1. Suspect when platelets count
falls by 50% or more after
starting heparin
2. Usually from day 5 onward ,
Unfractionated heparin appears sooner in patients with
recent exposure to heparin
3. TTT :
● Stop heparin
● Give parentral direct thrombin
inhibitor (argatroban)
Heparin Induced Thrompocytopenia ● Fondaparinux if adequate renal
HIT function
● Direct oral anticoagulants
(Rivaroxaban)
● Warfarin should not be used
until the platelet count has
recovered
 Thrombocytopenia Fall <30% or platelet count <10 × 109/L 0

30–50% fall or platelet count 10–19 × 109/L 1

>50% fall or platelet count 20–100 × 109/L 2

Timing of <5d with no previous heparin exposure 0

thrombocytopenia

Unfractionated heparin
4 Ts score parameters Possibly d5–10 but unclear, e.g. missing platelet counts 1

D5–10 or less if previous heparin exposure 2

Interpretation Thrombosis None 0

1. 0 - 3 points low probability <1% Progressive or recurrent thrombosis or skin lesions or suspected but unproven new
thrombosis
1

2. 4 - 5 intermediate 10 %
3. 6 - 8 high probability 50 % New thrombosis, skin necrosis, acute systemic reaction following heparin injection 2

Other cause of Probable other cause ( e.g DIC , Medications .. ) 0

thrombocytopenia

Possible other cause evident ( e.g sepsis ) 1

No other cause evident 2

Unfractionated heparin 1. Requirement for unusually large
doses (reaching 40 units / kg / hr ) of
heparin in order to achieve an aPTT
or ACT
2. Acquired antithrombin deficiency is
not uncommon post cardiac surgery
3. TTT :
Heparin resistance / ● Fresh Frozen Plasma15 ml/kg
AT deficiency ● Plasma-derived AT concentrate
 1. aPTT is <60 :
● Chest drain removal or
insertion -no need to stop
Unfractionated heparin heparin
● pacing wire removal – stop
heparin for 2 hours prior to
procedure and check aPTT is
<60
2. aPTT >60 STOP HEPARIN 2
Chest drains and Pacing wires
hours prior to procedures
 ● To warfarin : Warfarin and
heparin are simultaneously
administered for four to five
Unfractionated heparin
days until the INR is
therapeutic for a minimum of
24 hours

Transitioning between ● To a DOAC : start the DOAC

anticoagulants when a continuous infusion
of UFH is stopped
 1. Mechanism of action : inactivates
factor Xa
2. Dose : SubQ

Therapeutic :

Low Molecular Weight • < 2 months of age: 1.5

mg/kg BD SC
Heparin (LMWH) • > 2 months of age: 1 mg/kg
BD SC

Prophylactic ::

• < 2 months of age: 0.75

Enoxaparin mg/kg BD SC or 1.5 mg/kg
Clexane OD SC

• > 2 months of age: 0.5

mg/kg BD SC or 1mg/kg OD
SC (max 20mg BD or 40mg
OD)
 3. LMWH VS UFH :

Low Molecular Weight - Greater bioavailability, longer

Heparin (LMWH) duration af action, twice daily
only, low risk of HIT , low
incidence of osteoporosis
- Delayed onset of action (20-30
min) , less easily inactivated with
protamine sulfate
Enoxaparin
Clexane
 - To warfarin : Warfarin and
heparin are simultaneously
administered for four to five
Low Molecular Weight days until the INR is
Heparin (LMWH) therapeutic for a minimum of
24 hours

- To (DOACs) : administe the

Transitioning between oral agent within zero to two
anticoagulants
hours before the next
scheduled dose of LMW
heparin is due
 1. Mechanism of action : binds to
AT with a higher affinity ,
selective anti-Xa inhibitor
2. Dose : SubQ 0.1 mg /kg/dose
Fondaparinux OD
3. Advantages : long half life (OD)
, no HIT , monitoring not
required
4. Disadvantages : no antidote,
no monitoring
5. Monitor renal function for
possible adjustment
 - To fondaparinux : rapid
onset, stop the other agent
and start . from warfarin :
INR< 2
Fondaparinux
- From fondaparinux :
1. To warfarin : bridge till INR
reaches therapeutic level
Transitioning between 2. To DOACs : 24 hrs after the
anticoagulants last dose of fondaparinux
 1. Mechanism of action :
inhibits vitamin K epoxide
reductase
2. Monitoring : INR
3. In cases of bleeding : give
Vitamin K antagonists FFP , Vitamin K
4. INR < 1.5 before chest
drain or pacing wires
removal
5. Complete reversal of
anticoagulation will require
Warfarin
Marevan stopping 5 d before
surgery, for partial reversal
3d
 ● Drug interactions :
1. Phenobarbital decreases
effect of warfarin
2. Cephalosporins, Macrolides,
Vitamin K antagonists Acetaminophen,NSAIDs,Asp
irin increase risk of bleeding

Warfarin
Marevan
DOACs ● FDA approved 2010
Direct oral anticoagulants ● Direct factor Xa inhibitors
NOACs (e.g rivaroxaban )
Novel oral anticoagulants ● Direct thrombin inhibitors
(ie, dabigatran)
● No routine lab monitoring
 1. Mechanism of action : direct,
selective and reversible
inhibition of factor Xa (FXa) in
both the intrinsic and extrinsic
DOACS coagulation pathways
2. Indications in pediatrics (after
fontan, VTE , PE)
3. Other indications (adults,not
yet well established in peds )
● Non valvular AF
● Coronary artery disease
Rivaroxaban ● HIT

4. Dose :PO start from 1.1

mg/dose BD
DOACS ● Food has no significant effect
on rivaroxaban
● Contraindicated:
ketoconazole and other
azole-antimycotics
● Contraindicated if liver
disease with coagulopathy,
Rivaroxaban baseline PT>13sec
● Not used in Mechanical
valves
● Don’t prescribe if eGFR <15
DOACS ●
-
To warfarin :
UFH or LMWH + Warfarin till
target INR
● From warfarin : DC , start
when INR < 3
● DOAC to another DOAC : no
overlap needed
Transitioning between
anticoagulants
When to stop 1. Warfarin 2-4 days
2. Aspirin – Do not stop in shunt /
anticoagulation stent dependent circulation,
pre-operatively? other patients stop 7 days pre-op
3. Clopidogrel – Stop 7 days pre-op
or cardiac catheterization
4. UFH - stop 4 hours
5. LMWH 12 - 24 hours
6. Fondaparinux : Stop 2-4 days
before elective surgery
Overview of indications for anti-coagulation / antithrombotic therapy in cardiac patients
Immediate Post-operative
Post-op
Anticoagulation required? Long term
Operation anticoagulation
anticoagulation

BT / Central shunt / Yes Heparin Aspirin

Sano

Glenn No +_ aspirin , warfarin for

high risk

Fontan Yes Heparin Warfarin 6 months

Hybrid procedure with Yes Heparin Warfarin or LMWH +

PDA stent Aspirin or clopedogril
Overview of indications for anti-coagulation / antithrombotic therapy in cardiac patients

Post-op
Immediate Post-operative Long term
Operation anticoagulation
Anticoagulation required? anticoagulation

ASD / VSD / AVSD No

ASO No

TOF No

TAPVD No

Cardiomyopathy , EF<25 Warfarin may

with risk factors add aspirin
Overview of indications for anti-coagulation for Valve Surgery

Immediate
Post-operative Post-op anticoagulation Long term
Operation
Anticoagulation anticoagulation
required?

RV-PA valved conduits : No Yes Aspirin 3 months ,

Homograft / Contegra / consider warfarin in
free style high risk for thrombosis

Valve repair : No Yes Aspirin 3-6 months

annuloplasty ,
pericardial patch

Ross No Yes Aspirin 3 months

Mechanical valves Yes Heparin when bleeding Warfarin , INR 2-3 +_

stops Aspirin
 1. Before starting know the cost
& benefits of anticoagulations
2. While your patient is on
Take home message anticoagulant always check for
signs of bleeding / intracranial
hemorrage
3. Take care of undercoagulation
4. Always choose an agent you
are familiar with , can reverse if
needed
5. Before stoppage , consult
“ This is the reality of intensive care : at any point
we are about to harm as we are to heal. “

- Unknown