Warfarin skin necrosis occurs within the first 2 to 3 days after starting warfarin therapy because:

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Warfarin inhibits the synthesis of vitamin K-dependent coagulation factors (prothrombin, factors VII, IX, and X) and protein C, which is also a vitamin K-dependent protein. Protein C has a shorter half-life than prothrombin and is therefore depleted faster than the procoagulant factors. This leads to a transient hypercoagulable state before full anticoagulation is achieved. In patients with a deficiency of protein C, protein S, or antithrombin, this transient hypercoagulability can predispose them to developing skin necrosis due to thrombosis of small vessels in the skin. Skin necrosis typically occurs within the first 2 to 3 days after starting warfarin therapy.

Warfarin Skin Necrosis Occurs Within the First 2 to 3