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

Drug	Wisconsin Alumni Research Foundation
Mechanism
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

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 · t_1/2_β 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)