Warfarin Mechanism Detail — MFDS Part 1 MCQ

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ModeratePharmacologyWarfarin Mechanism DetailMFDS Part 1

Warfarin reduces the gamma-carboxylation and biological activity of vitamin K-dependent coagulation factors. Which molecular target is inhibited to produce this anticoagulant effect?

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Correct answer: C — Vitamin K epoxide reductase (VKORC1)

The correct answer is C. Warfarin inhibits vitamin K epoxide reductase, principally VKORC1, reducing regeneration of the active, reduced form of vitamin K. This impairs gamma-carboxylation and activation of factors II, VII, IX and X and the anticoagulant proteins C and S. The alternatives represent other antithrombotic mechanisms: COX-1 is irreversibly inhibited by aspirin; thrombin is directly inhibited by agents such as dabigatran; factor Xa is directly inhibited by drugs such as apixaban and rivaroxaban; and GPIIb/IIIa receptors are blocked by antiplatelet drugs such as abciximab. Warfarin does not directly inhibit an activated coagulation factor or platelet receptor.

Reference: Berkner KL et al. Vitamin K-Dependent Protein Activation: Normal Gamma-Glutamyl Carboxylation and Disruption in Disease. Int J Mol Sci, 2022 (VKORC1 regeneration of reduced vitamin K; warfarin inhibition). https://pubmed.ncbi.nlm.nih.gov/35628569/ — corroborated by Warfarin 5 mg tablets SmPC, section 5.1, eMC: https://www.medicines.org.uk/emc/product/14333/smpc