A patient is started on warfarin. During the first 48–72 hours, there is a transient PRO-thrombotic state before anticoagulation is achieved. This is because:

• A Warfarin activates Vitamin K reductase transiently before inhibiting it
• B Warfarin first activates thromboxane A2 production in platelets
• C Direct inhibition of antithrombin III during the loading phase
• D Protein C and Protein S (with shorter half-lives) are depleted before factors II, IX, and X are significantly reduced ✓

Explanation

Warfarin inhibits Vitamin K-dependent carboxylation of clotting factors II, VII, IX, X and anticoagulant proteins C and S. Protein C and S have much shorter half-lives (~6–8 hours and ~30 hours respectively) than procoagulant factors. They are depleted first, creating a transient hypercoagulable state before the full anticoagulant effect develops as factors II, IX, and X decline. This is why heparin overlap is required for at least 5 days when initiating warfarin therapy.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.