摘要
A 76-year-old patient was admitted to our hospital with dyspnea. His past medical history disclosed a 17-year duration of polycythemia vera with thrombocytosis; arterial hypertension; diabetes mellitus; hyperuricemia; auricular fibrillation; and chronic bronchitis. He had been treated with hydroxyurea, digoxin, allopurinol, and enalapril. Although pulmonary embolism was not demonstrated, at admission, as a result of the presence of thrombocytosis and arrhythmia, prophylactic treatment with subcutaneous enoxaparin, 60 mg twice daily, was prescribed. Five days after the first injection, two symmetric erythematous patches, 5 cm in diameter, were noted at the abdominal wall area coincident to the points of subcutaneous enoxaparin injection. During the following 24 h, the lesions enlarged and evolved to form purplish-blue necrotic plaques, 15 cm × 5 cm in diameter (Figs 1 and 2). The development of this localized side-effect led to the discontinuation of treatment with enoxaparin. A skin biopsy taken from the margin of the lesion showed multiple fibrin thrombi in the dermal microvasculature with ischemic necrosis of the overlying epidermis (Fig. 3). Routine laboratory testing showed: hemoglobin, 74 g/L; white blood cell count, 28.5 × 109/L; platelets, 1025 × 109/L; creatinine, 1.5 mg/dL; and uric acid, 11.8 mg/dL. Coagulation studies showed: prothrombin time ratio, 1.17; thromboplastin time ratio, 1.36; fibrinogen, 3.6 g/L; normal protein C; and negative lupic anticoagulant factor. contrast, protein S function was reduced: 56% (normal, 71- 142% ) with low free protein S (63% ; normal, 72- 139% ) and normal total protein S (protein S deficiency type III). Immu- noglobulin G (IgG) antiphospholipid antibody was normal, but IgM was increased to 4.25 (normal, < 3.1). Heparin-platelet factor 4 (PF4) antibodies were also demonstrated. There was no significant change in the platelet count throughout the patient s admission. The lesions were treated locally, and complete healing was observed after approximately 1 month. Skin necrosis is a rare complication of subcutaneous low-molecular- weight heparin injections. Heparin-induced skin necrosis is now thought to be caused by an antibody-mediated local prothrombotic condition associated with platelet activation and increased thrombin production. The association of heparinin duced skin necrosis with antibodies directed against PF4 is a well-established phenomenon. The concomitant participation of other procoagulant factors, however, has received little attention in the literature. The observation of heparin-induced skin necrosis should motivate a systematic search for the presence of anti-PF4 antibodies, but also for additional genetic or acquired procoagulant factors. As heparin-induced skin necrosis may be a marker for increased risk of systemic arterial or venous thromboembolism, an increased awareness regarding the significance of this potential side-effect is important in order to .avoid further potentially severe associated complications.
A 76-year-old patient was admitted to our hospital with dyspnea. His past medical history disclosed a 17-year duration of polycythemia vera with thrombocytosis; arterial hypertension; diabetes mellitus; hyperuricemia; auricular fibrillation; and chronic bronchitis. He had been treated with hydroxyurea, digoxin, allopurinol, and enalapril. Although pulmonary embolism was not demonstrated, at admission, as a result of the presence of thrembocytosis and arrhythmia, prophylactic treatment with subcutaneous enoxaparin, 60 mg twice daily, was prescribed. Five days after the first injection, two symmetric erythematous patches, 5 cm in diameter, were noted at the abdominal wall area coincident to the points of subcutaneous enoxaparin injection. During the following 24 h, the lesions enlarged and evolved to form purplish-blue necrotic plaques, 15 cm × 5 cm in diameter （Figs i and 2）. The development of this localized side-effect led to the discontinuation of treatment with enoxaparin. A skin biopsy taken from the margin of the lesion showed multiple fibrin thrombi in the dermal microvasculature with ischemic necrosis of the overlying epidermis （Fig. 3）.
