Explain the mechanism of warfarin and the importance of maintaining INR within a therapeutic range.

• A. Warfarin inhibits platelet aggregation via the P2Y12 receptor.
• B. Warfarin inhibits vitamin K epoxide reductase, reducing synthesis of vitamin K-dependent clotting factors; INR ensures therapeutic anticoagulation.
• C. Warfarin directly inhibits thrombin.
• D. Warfarin activates antithrombin III.

Answer: (B)

Warfarin works by blocking the recycling of vitamin K in the liver. Specifically, it inhibits vitamin K epoxide reductase, so reduced vitamin K isn’t regenerated. Without active vitamin K, the gamma-carboxylation of vitamin K–dependent clotting factors II, VII, IX, and X (and proteins C and S) is impaired, leading to production of clotting factors that are functionally inactive. This reduces the body's ability to form clots, producing anticoagulation that develops over several days as existing factors turn over.

The INR is used to monitor and guide this effect. It standardizes the prothrombin time across laboratories, reflecting how long the extrinsic pathway takes to clot and how strongly warfarin is suppressing clotting factor activity. Keeping the INR within a therapeutic range ensures enough anticoagulation to prevent events like stroke or DVT, while avoiding excessive bleeding risk. If the INR is too low, protection wanes; if it’s too high, bleeding can occur. The exact target range depends on the indication (often about 2.0–3.0, sometimes higher for mechanical heart valves). Diet, drug interactions, and metabolic factors can shift INR, so regular monitoring and dose adjustments are essential.