Which deficiency is classically associated with warfarin skin necrosis when starting anticoagulation?

Which deficiency is classically associated with warfarin skin necrosis when starting anticoagulation?

• A. Protein C deficiency
• B. Protein S deficiency
• C. Antithrombin deficiency
• D. Factor VII deficiency

Answer: (A)

Warfarin skin necrosis happens because starting warfarin creates a temporary imbalance: the natural anticoagulant protein C falls quickly due to warfarin’s effect on vitamin K–dependent proteins, while procoagulant factors decrease more slowly. Protein C has a relatively short half-life, so in someone with a deficiency of Protein C, this early drop is even more pronounced, allowing microvascular thrombosis to form in the skin and leading to necrosis. That rapid, initial prothrombotic shift is the classic trigger, which is why Protein C deficiency is the best answer. Protein S deficiency can also contribute to clotting risk, but it’s not the textbook driver of the skin necrosis being asked about. Antithrombin deficiency predisposes to thrombosis in general rather than specifically to this warfarin-induced phenomenon, and factor VII deficiency causes bleeding, not thrombosis, so they aren’t the classic associations for this scenario.

Warfarin skin necrosis happens because starting warfarin creates a temporary imbalance: the natural anticoagulant protein C falls quickly due to warfarin’s effect on vitamin K–dependent proteins, while procoagulant factors decrease more slowly. Protein C has a relatively short half-life, so in someone with a deficiency of Protein C, this early drop is even more pronounced, allowing microvascular thrombosis to form in the skin and leading to necrosis. That rapid, initial prothrombotic shift is the classic trigger, which is why Protein C deficiency is the best answer.

Protein S deficiency can also contribute to clotting risk, but it’s not the textbook driver of the skin necrosis being asked about. Antithrombin deficiency predisposes to thrombosis in general rather than specifically to this warfarin-induced phenomenon, and factor VII deficiency causes bleeding, not thrombosis, so they aren’t the classic associations for this scenario.