Which statement best describes warfarin's mechanism of action?

Which statement best describes warfarin's mechanism of action?

• A. Directly inhibits thrombin.
• B. Activates antithrombin III.
• C. Inhibits vitamin K epoxide reductase, reducing synthesis of vitamin K–dependent clotting factors II, VII, IX, X and proteins C and S.
• D. Inhibits platelet aggregation by blocking COX-1.

Answer: (C)

Warfarin acts as a vitamin K antagonist by inhibiting vitamin K epoxide reductase, the enzyme that recycles vitamin K to its active reduced form. Without active vitamin K, the liver cannot gamma-carboxylate glutamate residues on certain clotting factors, so the factors that are produced are undercarboxylated and function poorly. This directly reduces the activity of clotting factors II, VII, IX, and X, as well as the anticoagulant proteins C and S, leading to an overall anticoagulant effect. This mechanism is different from directly inhibiting thrombin or platelet function, which is what other classes of drugs do. Note that because some factors (and especially protein C and S) are affected early, there can be a transient prothrombotic state, and the full anticoagulant effect takes time to develop as existing clotting factors degrade.

Warfarin acts as a vitamin K antagonist by inhibiting vitamin K epoxide reductase, the enzyme that recycles vitamin K to its active reduced form. Without active vitamin K, the liver cannot gamma-carboxylate glutamate residues on certain clotting factors, so the factors that are produced are undercarboxylated and function poorly. This directly reduces the activity of clotting factors II, VII, IX, and X, as well as the anticoagulant proteins C and S, leading to an overall anticoagulant effect. This mechanism is different from directly inhibiting thrombin or platelet function, which is what other classes of drugs do. Note that because some factors (and especially protein C and S) are affected early, there can be a transient prothrombotic state, and the full anticoagulant effect takes time to develop as existing clotting factors degrade.