What is the mechanism of warfarin?

• A. Inhibits platelet aggregation.
• B. Direct thrombin inhibition.
• C. Increases fibrinogen synthesis.
• D. Inhibits vitamin K epoxide reductase.

Answer: (D)

Warfarin works by blocking the recycling of vitamin K in the liver. It inhibits the enzyme vitamin K epoxide reductase, which is needed to convert vitamin K to its active reduced form. Without active vitamin K, the gamma-carboxylation of clotting factors II, VII, IX, and X (and the regulatory proteins C and S) cannot occur properly. As a result, these clotting factors are produced in an inactive form and cannot participate effectively in coagulation, producing an anticoagulant effect.

Because existing clotting factors in the circulation must break down before the full anticoagulant effect appears, onset is delayed and monitoring with INR is used to gauge intensity. Warfarin is a vitamin K antagonist and does not directly inhibit thrombin, does not act by inhibiting platelets, and does not increase fibrinogen synthesis.