USMLE Step 2 Clinical Knowledge (CK) Practice Exam

Warfarin primarily inhibits the synthesis of vitamin K-dependent clotting factors in the liver. These factors include prothrombin (factor II), factor VII, factor IX, and factor X. Additionally, warfarin also inhibits the vitamin K-dependent proteins C and S, which play a crucial role in the regulation of coagulation and the prevention of thrombosis.

The rationale for warfarin's mechanism of action involves the interference with the enzyme epoxide reductase, which is necessary for reducing vitamin K to its active form. This reduction process is essential for the gamma-carboxylation of certain glutamic acid residues on these clotting factors, which is a critical modification for their functional activity. Without this carboxylation, the clotting factors cannot effectively participate in the coagulation cascade.

Therefore, the correct answer emphasizes warfarin's comprehensive inhibition of the aforementioned factors, demonstrating its role in anticoagulation therapy. Understanding this mechanism is pivotal for managing conditions such as atrial fibrillation and preventing venous thromboembolism.

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