1476: Autoimmune Hemolytic Anemia in Systemic Lupus Erythematosus: A Meta-analysis of Prevalence and Clinical Correlates

Background/Purpose: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread immune dysregulation and multi-organ involvement. Autoimmune hemolytic anemia (AIHA), marked by antibody-mediated red blood cell destruction, is a common hematological complication of SLE. The overlap of SLE and AIHA represents a distinct clinical phenotype with diagnostic challenges. This study examined the frequency of AIHA in SLE and its association with other clinical manifestations of SLE.

Methods: The systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and checklists. A comprehensive literature search was conducted using PubMed (1959–2025) with the keywords “systemic lupus erythematosus,” “lupus,” “hemolytic anemia,” “autoimmune hemolytic anemia,” “AIHA,” and “hematologic manifestations. Studies reporting the frequency of AIHA in SLE patients were screened, and eligible articles were included to estimate AIHA prevalence and assess associations with other clinical features of SLE. A random effects model was used to pool AIHA frequency across SLE studies, with forest plots generated for composite estimates and corresponding 95% confidence intervals (CI). Study heterogeneity was assessed using the I² statistic. Correlation analyses were performed to evaluate associations between AIHA and specific SLE features.

Results: Fifty-six studies reported the frequency of AIHA in 25,549 SLE patients. The overall AIHA prevalence was 12.5% (95% CI: 10.3-15.1) using a random-effects model, selected due to substantial inter-study heterogeneity (I² = 96%). While most patients were female, gender-stratified AIHA analyses were limited by inconsistent reporting. Across the included studies, Pearson Correlation Analysis showed that AIHA frequency was significantly correlated with a positive Coombs test (r=0.96, p< 0.001), leukopenia (r=0.79, p< 0.001), lymphopenia (r=0.78, p< 0.001), thrombocytopenia (r=0.79, p< 0.001), lupus nephritis (LN) (r=0.62, p< 0.001), serositis (r=0.76, p< 0.001), neuropsychiatric SLE (NPSLE) (r=0.63, p< 0.001) and thrombosis (r=0.88, p< 0.001).

Conclusion: This study demonstrates that AIHA is present in approximately 1 in 8 patients with SLE (12.5%) and that it frequently co-occurs with Coombs positivity, cytopenias, thrombosis, serositis, LN, and NPSLE—all key markers of major organ involvement. These findings support AIHA as a hallmark hematologic manifestation of SLE, with potential utility as a marker of disease burden and prognostic significance. Further prospective studies are warranted to define the prognostic implications of AIHA and its possible role in SLE disease stratification, monitoring, and therapeutic decision-making in SLE.