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Warfarin-induced skin necrosis (or, more generally, coumadin-induced skin necrosis or Anticoagulant-induced skin necrosis) is a condition in which skin and subcutaneous tissue necrosis (tissue death) occurs due to acquired protein C deficiency following treatment with anti-vitamin K anticoagulants (coumadins, such as warfarin). Warfarin necrosis is a rare but severe complication of treatment with warfarin or related anticoagulants. The typical patient appears to be an obese, middle aged woman (median age 54 years, male to female ratio 1:3).〔〔James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. ISBN 0-7216-2921-0.〕 This drug eruption usually occurs between the third and tenth days of therapy with warfarin derivatives.〔 The first symptoms are pain and redness in the affected area. As they progress, lesions develop a sharp border and become petechial, then hard and purpuric. They may then resolve or progress to form large, irregular, bloody bullae with eventual necrosis and slow-healing eschar formation. Favored sites are breasts, thighs, buttocks and penis,〔 all areas with subcutaneous fat.〔 In rare cases, the fascia and muscle are involved. Development of the syndrome is associated with the use of large loading doses at the start of treatment. ==Disease mechanism== Warfarin necrosis usually occurs three to five days after drug therapy is begun, and a high initial dose increases the risk of its development.〔 Heparin-induced necrosis can develop both at sites of local injection and - when infused intravenously - in a widespread pattern.〔 In warfarin's initial stages of action, inhibition of protein C and Factor VII is stronger than inhibition of the other vitamin K-dependent coagulation factors II, IX and X. This results from the fact that these proteins have different half-lives: 1.5 to six hours for factor VII and eight hours for protein C, versus one day for factor IX, two days for factor X and two to five days for factor II. The larger the initial dose of vitamin K-antagonist, the more pronounced these differences are. This coagulation factor imbalance leads to paradoxical activation of coagulation, resulting in a hypercoagulable state and thrombosis. The blood clots interrupt the blood supply to the skin, causing necrosis. Protein C is an innate anticoagulant, and as warfarin further decreases protein C levels, it can lead to massive thrombosis with necrosis and gangrene of limbs. Notably, the prothrombin time (or international normalized ratio, INR) used to test the effect of coumadins is highly dependent on factor VII, which explains why patients can have a therapeutic INR (indicating good anticoagulant effect) but still be in a hypercoagulable state.〔 In one third of cases, warfarin necrosis occurs in patients with an underlying, innate and previously unknown deficiency of protein C. The condition is related to purpura fulminans, a complication in infants with sepsis (blood stream infection) which also involves skin necrosis. These infants often have protein C deficiency as well. There have also been cases in patients with other deficiency, including protein S deficiency, activated protein C resistance (Factor V Leiden) and antithrombin III deficiency. Although the above theory is the most commonly accepted theory, others believe that it is a hypersensitivity reaction or a direct toxic effect.〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Warfarin necrosis」の詳細全文を読む スポンサード リンク
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