When Prophylaxis Turns Pathologic: A Case of LMWH-Induced Necrosis with Secondary Cellulitis

Abstract

Introduction and importance: Low-molecular-weight heparins (LMWHs) are widely used for thromboprophylaxis during pregnancy and postpartum due to their favorable safety profile. However, rare immune-mediated adverse events, such as delayed-type hypersensitivity reactions leading to skin necrosis, may occur and can be complicated by secondary infections. Awareness of this rare complication is important for timely diagnosis and management.
Case presentation: We report the case of a 40-year-old postpartum woman who developed painful necrotic skin lesions one week after cesarean delivery while receiving prophylactic enoxaparin. Lesions appeared at previous injection sites on the abdomen and left arm, with associated erythema and tenderness. Laboratory findings showed leukocytosis, elevated CRP, and ESR, with normal platelet counts, excluding heparin-induced thrombocytopenia. The clinical features were consistent with LMWH-induced delayed-type hypersensitivity complicated by cellulitis. Enoxaparin was discontinued, and the patient was treated with apixaban, intravenous antibiotics, daily wound care, and partial surgical debridement. She improved and was discharged in stable condition.
Clinical discussion: Although LMWHs are considered safe, clinicians should recognize that delayed-type hypersensitivity reactions may mimic infection or thrombotic conditions, complicating diagnosis. Necrotic skin lesions typically appear 5–14 days after LMWH initiation, reflecting T-cell-mediated vascular injury. Early recognition and discontinuation of LMWH, alongside alternative anticoagulation and infection management, are crucial to prevent morbidity. Literature indicates that such cases remain extremely rare, particularly in postpartum patients, underscoring the need for heightened clinical vigilance.
Conclusion: LMWH-induced skin necrosis with secondary cellulitis is a rare but serious complication that requires prompt recognition and management. Clinicians should maintain a high index of suspicion in patients presenting with necrotic lesions at injection sites, especially in the postpartum setting, to ensure timely intervention and favorable outcomes.