AUTHOR=Xia Wenxia , Lu Jialing , Hou Junjie , Zhou Jihao , Lin Haiqing , Lai Xiaoxuan , Zhang Xinyou , Zhang Ruiting , Ke Peng 

TITLE=Case Report: Severe autoimmune hemolytic anemia in an elderly patient caused by warm-reactive IgG and IgA autoantibodies

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1664498

DOI=10.3389/fimmu.2025.1664498

ISSN=1664-3224

ABSTRACT=BackgroundAutoimmune Hemolytic anemia (AIHA) a relatively uncommon form of hemolytic anemia, which is characterized by the presence of autoantibodies directed against erythrocyte surface antigens, most frequently of the IgG isotype. A positive Direct Antiglobulin Test (DAT) is a key diagnostic criterion for AIHA. However, when hemolysis involves multiple autoantibodies, the standard DAT (polyspecific, anti-IgG + C3) may fail to detect certain antibodies, potentially delaying appropriate treatment.Cases presentationWe reported one patient with severe AIHA mediated by IgG and IgA autoantibodies was successfully treated with Multi-drug combination regimens. A 58-year-old female was admitted to the hospital presenting with a history of fatigue, jaundice and soy sauce-colored urine for one day. Upon admission, a complete blood count revealed a critically low hemoglobin level of 41 g/L and a life-threatening condition. Initially diagnosed with IgG-mediated AIHA via standard DAT, the patient showed suboptimal response to glucocorticoids, intravenous immunoglobulin (IVIG), and transfusion support. Subsequently, through the extended DAT (monospecific, anti-IgA, anti-IgG, anti-IgM, and anti-C3) test results, the patient was diagnosed as severe AIHA mediated by IgG and IgA. Based on extended DAT results, the treatment plan was modified to include combination therapy with dexamethasone, rituximab, cyclosporine, and bortezomib, alongside intensified plasma exchange.ConclusionsThe extended DAT testing is recommended for all patients with clinical and laboratory evidence of acute hemolysis. Early detection helps in avoiding further investigations and provide efficient management. Severe AIHA mediated by multiple autoantibodies requires early intensive combination therapy, including immunosuppressive agents, IVIG and plasma exchange.