Autoimmune Hemolytic Anemia in Non-Hodgkin's Lymphoma: Pathogenesis, Diagnosis, and Management

Autoimmune hemolytic anemia (AIHA) is an acquired hemolytic disorder caused by autoantibodies and/or complement-mediated destruction of red blood cells (RBCs), often driven by dysregulated B lymphocyte activity. A notable clinical association exists between AIHA and lymphoproliferative disorders (LPD), particularly chronic lymphocytic leukemia, and non-Hodgkin's lymphoma (NHL). To summarize the clinicopathological link, prevalence, pathogenesis, and management strategies of AIHA associated with NHL. This narrative review synthesizes evidence from 20 peer-reviewed studies published between 2011 and 2024, identified through PubMed, Google Scholar, and manual citation tracking. Eligible studies were restricted to English-language articles addressing the prevalence, pathogenesis, clinical features, diagnosis, or treatment of AIHA in NHL. Approximately 7%-10% of NHL patients develop coexisting AIHA, while up to 20% of AIHA patients are eventually diagnosed with lymphoma. The reported incidence of AIHA among NHL patients varies widely (0.23%-15.7%), reflecting methodological and population differences. Proposed mechanisms include chronic antigen stimulation and dysregulated antibody production. The coexistence of both conditions complicates management: Treatment generally prioritizes NHL-directed therapy, while glucocorticoids and rituximab are commonly used for AIHA control. AIHA and NHL share overlapping immunopathological pathways with important clinical implications. Early recognition of AIHA in NHL is essential to optimize patient outcomes. Future priorities include developing biomarkers to identify high-risk patients and conducting large-scale randomized trials to validate complement inhibitors for cold agglutinin disease (CAD).