Warfarin necrosis is acquired protein C deficiency due to treatment with the vitamin K inhibitor anticoagulant warfarin. It is a feared (but rare) complication of warfarin treatment. The syndrome typically occurs during the first few days of warfarin therapy, often in association with the administration of a large initial loading dose of the drug. In initial stages of action, inhibition of protein C may be stronger than inhibition of the vitamin K-dependent coagulation factors (II, VII, IX and X), leading to paradoxical activation of coagulation and necrosis of skin areas. It occurs mainly in patients with a deficiency of protein C. Protein C is an innate anticoagulant, and as warfarin further decreases protein C levels by inhibiting vitamin K, it can lead to massive thrombosis with necrosis and gangrene of limbs.

Since heparin and its low-molecular weight variant act by a different mechanism than warfarin, these drugs can be used to prevent clotting during the first few days of warfarin therapy and thus prevent warfarin necrosis.

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Hematology