Influenza‐Induced Hemolysis in Hemoglobin H Disease: A Case Report

Hemoglobin H (HbH) disease is a rare form of alpha‐thalassemia caused by deletion or mutation of three alpha‐globin genes, resulting in the formation of beta‐globin tetramers and chronic hemolysis. Disease severity is variable, and physiologic stressors such as infection can precipitate acute hemolytic crises. Adult presentations are uncommon and often occur in patients lost to longitudinal care. We report a case of severe viral‐induced hemolysis in an adult with HbH disease following influenza infection. A 40‐year‐old Laotian male presented with one week of progressive fatigue and altered mental status after developing an upper respiratory tract infection. He had not received the annual influenza vaccination. On examination, he was jaundiced with hepatosplenomegaly. Labs revealed severe microcytic anemia (hemoglobin 3.5 g/dL and mean corpuscular volume 77 fL), hyperbilirubinemia (total bilirubin 7.4 mg/dL and direct bilirubin 2.8 mg/dL), and elevated transaminases (AST 674 U/L and ALT 370 U/L). Direct Coombs test was negative, and imaging excluded acute intracranial or intra‐abdominal pathology. Influenza A infection was confirmed. The patient required intensive care admission, transfusion of packed red blood cells, and antiviral therapy with oseltamivir. High‐performance liquid chromatography detected a hemoglobin variant suggestive of hemoglobin H (HbH) or Hb Barts but was unable to quantify the HbH fraction. The report noted suspicion for Hb Constant Spring; however, molecular genotyping was not performed. Prior records confirmed HbH disease but did not include genotype or quantitative HbH data. The patient improved with supportive care and was discharged with hematology follow‐up. This case illustrates that HbH disease may present in adulthood with life‐threatening, infection‐induced hemolysis. Recognition of hemoglobinopathies in at‐risk populations, particularly individuals of Southeast Asian ancestry, remains critical. Preventive strategies, including annual influenza vaccination, genetic confirmation, and sustained hematology follow‐up, are essential to reducing avoidable morbidity.