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

Mixed autoimmune hemolytic anemia (AIHA) may show temporal shifts in its predominant effector mechanism.

We serially assessed clinical course, direct antiglobulin test (DAT) specificity, cold agglutinin activity, complement markers, marrow findings, and immunofixation after rituximab response.

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.

Serial reassessment may identify complement-mediated relapse in mixed AIHA.

Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.