IMMUNOPATHOLOGICAL EVENTS OF ADVERSE CUTANEOUS REACTIONS TO COUMARIN AND HEPARIN

We here describe a female patient with thromboembolic disease, who exh ibited allergic reactions to heparin and who developed a large necroti c area on the abdomen when coumarin treatment was instituted. On immun ohistology of the necrotic lesion, tumour necrosis factor a was marked ly expressed, with decreasing intensity towards the central necrotic p art of the lesion, Furthermore, endothelial cell adhesion molecule exp ression was upregulated, particularly in the haemorrhagic zone at the periphery of the lesion, These findings suggest that the pathology of coumarin necrosis is mediated via tumour necrosis factor alpha-associa ted inflammatory events, after activation of the coagulation pathway d ue to an inherited or transiently induced, acquired protein C-deficien cy. In view of these findings, we propose that patients be treated in the future with tumour necrosis factor a antagonists such as pentoxify lline.