Safety and clinical impact of least-incompatible transfusions in autoimmune hemolytic anemia: a real- world multicenter study

Background Red blood cell transfusion in Autoimmune Hemolytic Anemia (AIHA) poses significant clinical challenges due to pan-reactive autoantibodies that interfere with cross-matching, often raising concerns regarding the safety of transfusing serologically "incompatible" blood. Methods This retrospective multicenter study evaluated the frequency, management criteria, and safety profile of red blood cells transfusions in a cohort of adult patients affected by AIHA, with a specific focus on the "least incompatible" units. Results We analyzed 93 adult patients diagnosed with AIHA at two hematology referral centers in Palermo, Italy, between 2020 and 2025. Transfusion support was required in 31.2% (N = 29) patients. Decisions were mainly guided by a "double trigger" of low hemoglobin (mean 6.3 g/dL) and symptoms of tissue hypoxia, rather than by fixed hemoglobin thresholds. Notably, 61.1% of characterized units were serologically "incompatible" due to autoantibodies. Despite this, the adverse reaction rate was extremely low (1.2% per unit), with no hemolytic reactions recorded. This safety profile was likely supported by concomitant immunosuppressive therapy (89.6% of transfused patients), acting as "biological premedication". Splenomegaly was identified as a marker for higher transfusion dependence (41.2% vs 29.5%). Conclusions Transfusion in AIHA is a safe and effective life-saving measure when managed with appropriate immunohematological oversight. The use of "least incompatible" blood does not lead to hemolysis when alloantibodies are excluded, and clinical management should rely on symptom-based triggers while recognizing splenomegaly as a potential indicator of refractory disease