IgA driven autoimmune hemolytic anemia: a monocentric Italian report and literature review

Abstract

Background - Atypical autoimmune hemolytic anemias (AIHA) include DAT-negative forms and those driven by IgA autoantibodies. IgA-mediated AIHA is rare, with limited evidence on clinical severity and management beyond first-line steroids. We revised our series of IgA-mediated AIHA and reviewed the literature.

Material and methods - We retrospectively evaluated patients with IgA-positive AIHA followed at a tertiary hematologic center in Milan since May 1978. Published reports from 2010 to January 28, 2025 were also reviewed.

Results - Thirteen patients with IgA-mediated AIHA were identified among 409 AIHA cases. Median age was 60 years, and 69.2% were female. Fatigue was the most common symptom; mean hemoglobin was 7.9 g/dL. Dual IgA/IgG positivity occurred in 69.2%, while triple IgA/IgG/IgM positivity occurred in 7.7%. All but one patient received corticosteroids, 33% rituximab, 16.6% IVIg, and 23.1% transfusions. One patient received bortezomib followed by mycophenolate mofetil and plasma exchange. During a median follow-up of 36 months, 63.6% relapsed. Infections and thrombotic events occurred in 16.7% each, with no deaths. The literature review included 35 patients from 19 studies. Most were female (62%), aged 3 months to 77 years. Tachycardia and dyspnea were the most common symptoms; mean hemoglobin was 5.6 g/dL. DAT showed dual IgA/IgG or IgA/IgM positivity in 54.3%. Corticosteroids were administered to all reported patients, IVIg and rituximab to 14% and 23%, respectively. Splenectomy was performed in 6%, and 93% received transfusions. Infections occurred in 14%, thrombotic events in 7.1%, and one patient was refractory and died.

Discussion - IgA-mediated AIHA is a rare, heterogeneous subtype characterized by frequent dual antibody positivity, suboptimal corticosteroid response, and substantial risks of relapse and complications, requiring careful monitoring and individualized management. These findings highlight the need for improved recognition of IgA-mediated disease and prospective studies to define optimal second-line therapies and outcomes in affected patients.