Immunopathological events of adverse cutaneous reactions to coumarin and heparin

We here describe a female patient with thromboembolic disease, who exhibited allergic reactions to heparin and who developed a large necrotic area on the abdomen when coumarin treatment was instituted. On immunohistology of the necrotic lesion, tumour necrosis factor alpha was markedly expressed, with decreasing intensity towards the central necrotic part of the lesion. Furthermore, endothelial cell adhesion molecule expression 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-associated inflammatory events, after activation of the coagulation pathway due to an inherited or transiently induced, acquired protein C-deficiency. In view of these findings, we propose that patients be treated in the future with tumour necrosis factor alpha antagonists such as pentoxifylline.