Rapidly Progressive and Severe Hemolytic Anemia Associated With Epstein-Barr Virus: A Case Report

Epstein-Barr virus (EBV) infection is rarely associated with severe hemolytic anemia.We report a case of a 41-year-old woman with sickle cell trait who developed rapidly progressive hemolytic anemia following travel to Guinea.She presented with fever, jaundice, abdominal pain, and splenomegaly.Laboratory evaluation revealed severe hemolysis, with hemoglobin declining from 11.4 g/dL to 4.6 g/dL, complicated by hemodynamic instability and acute kidney and liver injury.Despite a reported history of malaria, repeated blood smears and Plasmodium polymerase chain reaction (PCR) testing were negative.The initial direct antiglobulin test (DAT) was negative, but repeat testing became positive for complement C3d, while cold agglutinin testing remained negative.EBV serology and polymerase chain reaction findings raised suspicion for EBV-associated hemolysis, although a definitive causal relationship could not be established.The patient required multiple red blood cell transfusions, corticosteroids, and supportive care, with gradual clinical improvement.This case highlights the diagnostic challenges of severe hemolytic anemia with evolving immunohematologic findings.It emphasizes the importance of repeat DAT testing and the consideration of EBV as a potential associated infection.