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

1.Expectant	· i.e. drug washout -> regenerate Vit K -> regenerate clotting factors · t_1/2β 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
2.FFP	· Contains all clotting factors · IV 15-30mL/kg (or 2-4mL/kg if with prothrombinex) · Also give Vit K to avoid rebound anticoagulation
3.Prothrombinex	· Contains factors 2, 9, 10 · IV 25-50 units/kg · Also give Vit K to avoid rebound anticoagulation
4.FEIBA	· Contains active factor 7a, inactive factors 2,9,10 · IV 50-100 units/kg · Also give Vit K to avoid rebound anticoagulation
5.Novoseven	· 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