Objective: To investigate detection strategies for autoantibodies coexisting with alloantibodies and alloantibody-like specific antibodies in patients with autoimmune hemolytic anemia (AIHA), providing a theoretical basis for formulating safe and effective transfusion protocols in complex crossmatching scenarios.Methods: Serum autoantibodies and combined antibodies were detected using a combination of saline method, classic anti-human globulin test (Coombs test), and microcolumn gel assay. Antibody specificity and titer were determined through panel cell reaction pattern analysis, absorption/elution tests, and antibody titration.Results: Serum analysis revealed the presence of autoantibodies, anti-E alloantibody (titer: 1), anti-Wra alloantibody, and an antibody mimicking anti-Ce specificity (titer: 4). Crossmatch tests showed that the strong agglutination (2+) in the major crossmatch with group A, CCDee washed red blood cells (RBCs), weak agglutination (±) in the major crossmatch with group A, ccDEE washed RBCs. Consequently, 2 units of group A, ccDEE washed RBCs were transfused. The patient exhibited a satisfactory increase in hemoglobin post-transfusion, confirming transfusion efficacy without adverse reactions.Conclusion: In patients with multiple coexisting antibodies, priority must be given to excluding autoantibody interference before selecting the most compatible RBCs for transfusion based on antibody affinity and clinical urgency. The combined application of serological techniques and individualized transfusion strategies enhances transfusion safety in patients with complex serology.