Diagnostic utility of peripheral blood smear in fatal hemophagocytic lymphohistiocytosis complicating severe falciparum malaria in pregnancy: a case report and review of the literature

Abstract

Malaria, a common public health concern in endemic regions, poses significant risks during pregnancy and can rarely trigger secondary hemophagocytic lymphohistiocytosis (sHLH), a life-threatening hyperinflammatory condition. It is characterized by a cytokine storm and hyperactive macrophage-mediated phagocytosis of blood cells. To our knowledge, only one case of malaria-associated sHLH in pregnancy has been reported, where malaria was an incidental finding in an HIV-confounded presentation. We describe the first case of sHLH in pregnancy primarily triggered by malaria. This case was uniquely diagnosed via peripheral blood morphology, without bone marrow biopsy, and was accompanied by a leukoerythroblastic reaction on smear examination. A 20-year-old primigravida Ethiopian woman presented in her third trimester with intermittent high-grade fever, tachycardia, tachypnea, and splenomegaly. Laboratory findings revealed bicytopenia (anemia and thrombocytopenia), leukocytosis, and Plasmodium falciparum on peripheral smear. Despite resuscitation, intravenous artesunate, and broad-spectrum antibiotics, her condition deteriorated rapidly, culminating in fatal cardiac arrest within hours. Postmortem reevaluation of the peripheral smear demonstrated definitive hemophagocytic features, including phagocytosed erythrocytes, suggesting the diagnosis of sHLH. sHLH in pregnancy is often overlooked due to nonspecific symptoms mimicking common conditions and limited access to diagnostic criteria in resource-limited settings. In this case, delayed recognition likely contributed to mortality. While rare, identifying hemophagocytic histiocytes on peripheral smears is critical. Laboratory personnel play a vital role in flagging these morphological anomalies. Strengthening this collaboration, combined with heightened clinical suspicion, is essential to reducing diagnostic delays and facilitating life-saving intervention.