Necrosis of skin induced by coumarin in a patient deficient in protein S.

Abstract

weeks plasma total thyroxine and thyroid stimulating hormone concentrations were normal. He had no diarrhoea or allergic symptoms and was more active and lively. Iodine supplements were stopped. After eight weeks his response to thyrotrophin releasing hormone was normal. He had gained 1 5 kg in weight and 2 0 cm in height.

Warfarin-Induced Skin Necrosis in a Patient with Heparin-Induced Thrombocytopenia: Two Diseases or One?

“…In early descriptions of WISN, the patients demonstrated abnormalities of the natural anticoagulant pathway, such as congenital deficiency of protein C, protein S, or antithrombin III [1, 3.] This observation led to the idea that WISN occurred because of the more rapid decrease in the level of the major natural anticoagulant factor (protein C; half-life 6 h) compared with the level of the major procoagulant factor (prothrombin; half-life 72 h) during warfarin initiation.…”

“…As initially determined in patients with hereditary thrombophilia, the proposed theoretical mechanism of WISN is that necrosis occurs during a transient prothrombotic state due to the short half-life of the natural anticoagulant protein C (half-life 6 h) compared to the half-life of the major procoagulant factor prothrombin (half-life 72 h) [1,2,3]. Despite this proposed mechanism, most patients with WISN have no identifiable hereditary hypercoagulable state [4].…”

Skin Necrosis Induced by Coumarin Congeners

“…4,15,18 Sites are random but usually involve areas with abundant subcutaneous tissue, such as the breast, abdomen, buttocks, and thighs. 1,4,11,15 Other sites include the arms, 11,15,25 hands, 15,25,27 feet, 3,14,15,18,26,27 extremities, 3,6,15 nose, 15 and penis. 7,16 Single lesions are most prevalent.…”

“…1,13 The popular hypothesis that coumarin congeners are themselves toxic to the vascular endothelium of the skin lacks convincing proof. 1,2,4,13,20 Probable contributory factors (whose precise roles remain ill-defined) include congenital or acquired deficiencies of protein C, protein S, and antithrombin III, 3,6,8,10,14,21 G20210A mutation of the prothrombin gene, 19 and heparin-induced thrombocytopenia.…”

“…But if the necrosis becomes fully developed, it might need débridement, resection (breast), skin grafting, or amputation of affected extremities. 6,13,21,22,24,26 Topical or systemic antibiotics are indicated to control or eradicate infection of involved sites. 11,21,23 Use of fibrinolytic agents, corticosteroids, vasodilators, hypothermia (ice packs), vitamin C, and sympathetic nerve block has not shown benefit.…”