Warfarin inhibits VKORC1, reducing gamma-carboxylation of glutamate residues in certain coagulation factors. Which factors are affected?

• A. Factors II, VII, IX, X
• B. Factors III, VII, IX, X
• C. Factors III, VII, VIII, X
• D. Factors II, VII, VIII, X

Answer: (D)

Warfarin blocks VKORC1, which stops the recycling of reduced vitamin K needed for gamma-carboxylation. Without this modification, certain clotting factors cannot bind calcium properly and become active on phospholipid surfaces. The factors that depend on this vitamin K–driven gamma-carboxylation are II (prothrombin), VII, IX, and X. Factor VIII does not require this process, so it is not affected by warfarin. Therefore, the factors affected are II, VII, IX, and X.