Complement-Dominant Relapse of Mixed Autoimmune Hemolytic Anemia After Rituximab Response.

INTRODUCTION: Mixed autoimmune hemolytic anemia (AIHA) may show temporal shifts in its predominant effector mechanism. METHODS: We serially assessed clinical course, direct antiglobulin test (DAT) specificity, cold agglutinin activity, complement markers, marrow findings, and immunofixation after rituximab response. RESULTS: During winter relapse, the previously identified κ-restricted CD20-positive population was no longer detectable by marrow flow cytometry. Hemolysis was cold-reactive and complement-dominant. Hemoglobin increased without transfusion after sutimlimab, with C4 recovery and total hemolytic complement activity (CH50) suppression despite persistent cold agglutinin activity. Immunofixation later identified IgG-κ and IgM-κ monoclonal proteins. CONCLUSIONS: Serial reassessment may identify complement-mediated relapse in mixed AIHA. UNLABELLED: Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.