2012B01 How does warfarin exert its anticoagulant effect?
What methods can be used to reverse the effects of warfarin prior to surgery?

 

List:

·      Warfarin effect

·      Warfarin reversal

 

Warfarin:

Drug

Wisconsin Alumni Research Foundation

Mechanism

Factors affected (half life)

·  Anticoagulants: II (60h), VII (6h), IX (24h), X (36h)

·  Procoagulants: protein C (8h), protein S (30h)

Timeline of effect

·  Initial procoagulant effect

o Short half lives of procoagulants (proteins C & S)

o Long half lives of most important anticoagulants (Factors II, X)

·  Then anticoagulant effect

o Onset ~8-12 hours

o Peak ~3 days

o Duration ~5 days

 

Reversal:

Considerations

·  Depends upon urgency of surgery

·  Depends if actively bleeding

·  Check INR shortly pre-op to ensure adequate

Stop and wait

·  Time 3-5 days

·  t1/2β 40 hours

·  Need drug elimination + production of new coag factors

·  ↑Duration if: Vit K deficient e.g. malnourished, CYP inhibitor (e.g. cimetidine), CYP competition e.g. amiodarone

·  ↓Duration if: CYP inducer (e.g. barbiturates)

Vitamin

·  PO 1-2mg for effect in 12-24 hours

·  IV 5-10mg for effect in 6-12 hours

Blood products

·  Effect immediate

·  FFP 10-15mL/kg (note risk of APO); or

·  FFP 2-4mL/kg + prothrombinex (factors 2, 9, 10) 25-50 units/kg

·  +/- Activated Factor 7 (if ↑↑INR and bleeding)

 

 

 

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