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



·     Warfarin effect

·     Warfarin reversal




Wisconsin Alumni Research Foundation


Factors affected (half life)

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

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

Timeline of effect

·     Initial procoagulant effect

o Short half lives of anticoagulant protein C

o Long half lives of procoagulants II and X (most important)

·     Then anticoagulant effect

o Onset ~8-12 hours

o Peak ~3 days

o Duration ~5 days




·         i.e. drug washout -> regenerate Vit K -> regenerate clotting factors

·         t1/2β 40 hours -> offset in 5 days

·         ↑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)

·         Can operate immediately if a) low risk of bleeding b) benign consequences of bleeding c) easily compressible site

2.Vitamin K

·         i.e. replenish substrate -> regenerate clotting factors

·         PO 1-2mg for effect in 12-24 hours

·         IV 5-10mg for effect in 6-12 hours


·         Contains all clotting factors

·         IV 15-30mL/kg (or 2-4mL/kg if with prothrombinex)

·         Also give Vit K to avoid rebound anticoagulation


·         Contains factors 2, 9, 10

·         IV 25-50 units/kg

·         Also give Vit K to avoid rebound anticoagulation


·         Contains active factor 7a, inactive factors 2,9,10

·         IV 50-100 units/kg

·         Also give Vit K to avoid rebound anticoagulation


·         Activated Factor 7a

·         IV 50mcg/kg

·         Given in addition to FFP and/or prothrombinex

·         Only if persistent uncontrollable haemorrhage despite all other physiological, pharmacological and surgical efforts



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