Enoxaparin, a low-molecular-weight heparin used to treat and prevent deep venous thrombosis, has been evaluated in several clinical trials [1, 2]. The wide use of the drug makes it imperative that possible side effects, including skin reactions, be studied [3, 4]. We report the rare occurrence of skin necrosis that developed after enoxaparin administration. To our knowledge, previous reports of side effects of enoxaparin have described local skin inflammation and pruritis, but not necrosis. One report [5] noted that a different low-molecular-weight heparin caused skin necrosis. We surveyed approximately 8000 subcutaneous injections of enoxaparin (40 mg once a day or 20 mg twice a day) administered in the Meir General Hospital in Kfar-Saba, Israel, in 1993-1994. The only remarkable complications we identified were two cases of skin necrosis.

Patient 1, a 59-year-old woman, had surgery for myoma of the uterus. Because of her history of atrial fibrillation, treatment with enoxaparin, 40 mg in a single daily subcutaneous injection, was initiated. The drug was given alternately in the right and left arms. Six days later, the injection sites on both arms became red, tender, and indurated. A small black area, 25 mm in diameter, appeared on the left arm. Examination of a biopsy specimen of the lesion indicated severe vasculitis in the dermis and in the dermal-epidermal junction. Results of tests of blood clotting and blood count were within normal ranges. Enoxaparin treatment was discontinued, and the necrotic wound was treated with silver sulphadiazine cream. After local debridement, the wound was allowed to close spontaneously.

Patient 2 was a 34-year-old women in her 42nd week of pregnancy. She had a cesarean delivery because of rupture of the uterus and fetal distress. When deep venous thrombosis developed in her right foot after surgery, the patient was treated with 40 mg of subcutaneous enoxaparin injections once a day. The drug was given periumbilically or in either arm. A purple-red, tender area that appeared in the periumbilical region 10 days later became progressively necrotic (Figure 1). Examination of a wedge biopsy specimen showed epidermal necrosis and hyalinized vessels with mononuclear perivascular infiltration in the dermis. After local treatment with silver sulphadiazine cream, the necrotic wound was debrided and left to close spontaneously.

View larger version (114K): [in this window] [in a new window]   Figure 1. Necrosis in periumbilical area of patient 2 that developed after treatment with enoxaparin.

Skin necrosis occurring after administration of a low-molecular-weight heparin is rare, and the pathogenesis of this complication is not well understood. Our experience may alert medical personnel to the possibility of such a side effect.