Warfarin (Coumadin) primarily functions by inhibiting which Vitamin?

• A. Vitamin A
• B. Vitamin B
• C. Vitamin C
• D. Vitamin K

Answer: (D)

Warfarin works by antagonizing vitamin K, blocking the recycling of this vitamin through the vitamin K epoxide reductase enzyme. This prevents conversion of vitamin K to its active reduced form, leading to a shortage of functional vitamin K in the liver. Without sufficient reduced vitamin K, the gamma-carboxylation of glutamic acid residues on certain clotting factors cannot occur, so factors II, VII, IX, and X, along with proteins C and S, are produced in an inactive form that cannot effectively bind calcium or phospholipid surfaces. The result is a dampened coagulation cascade and a prolonged PT/INR. The effect depends on existing factor stores and vitamin K cycling, which is why dietary vitamin K or other drugs that affect vitamin K can alter warfarin’s action. Vitamins A, B, and C do not drive this gamma-carboxylation step, so they are not the target of warfarin.