Recurrent Mixed Autoimmune Hemolytic Anemia With Evans Syndrome and High-Risk Relapse Features: A Case Report

Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disorder characterized by immune-mediated red blood cell destruction, often posing diagnostic and therapeutic challenges, particularly in patients with multiple comorbid conditions. We report a complex case of recurrent mixed AIHA occurring in the setting of Evans syndrome, human immunodeficiency virus (HIV) infection, metastatic malignancy, and recent exposure to an immune checkpoint inhibitor. The patient presented with profound anemia and laboratory evidence of hemolysis, with a positive direct antiglobulin test demonstrating both IgG and complement (C3) involvement, consistent with mixed AIHA. The clinical course was marked by multiple relapses despite initial treatment with corticosteroids, intravenous immunoglobulin, and transfusion support, ultimately requiring escalation to rituximab for sustained hematologic stabilization. Notably, the disease course demonstrated discordant recovery patterns between hemoglobin and platelet counts, reflecting complex immune dysregulation. This case highlights the challenges in managing mixed AIHA with overlapping risk factors and underscores the potential role of immune checkpoint inhibitors and chronic immune activation in precipitating or exacerbating autoimmune cytopenias. It also emphasizes the importance of early recognition of high-risk features, including severe anemia and concomitant thrombocytopenia, which may warrant prompt escalation to second-line therapy. Further investigation is needed to better define optimal treatment strategies and the underlying mechanisms driving relapse in this population.