Transfusion without fear: Real-world outcomes in warm autoimmune hemolytic anemia challenge historical hesitations

Abstract Introduction Warm autoimmune hemolytic anemia (WAIHA) is an acquired autoimmune disorder characterized by IgG-mediated hemolysis of red blood cells (RBC) due to the presence of a panagglutinin autoantibody. During hemolytic crises, patients may develop life-threatening anemia, requiring urgent RBC transfusion. However, transfusion in WAIHA presents unique clinical challenges. The broad reactivity of panagglutinins renders most donor units serologically incompatible, complicating crossmatching and raising concerns about hemolytic transfusion reactions. While several institutional and case-based studies have described the safety of transfusion in WAIHA, national data characterizing transfusion patterns, complications, and outcomes in this population remain sparse. We carried out this study to characterize real-world transfusion practices in WAIHA and support evidence-based clinical decision-making. Methods We conducted a retrospective cohort study using data from the National Inpatient Sample (NIS) database from 2018 to 2021. Adult hospitalizations with a primary diagnosis of WAIHA were identified and stratified by whether or not they received nonautologous packed RBC transfusions. Primary outcomes included inpatient mortality, length of stay (LOS), total hospitalization costs, and discharge disposition. Secondary outcomes included acute transfusion-related complications. Multivariable logistic and linear regression models were used to adjust for age, sex, race, primary payer, and ZIP code-based income quartile. Results Among 313 adult hospitalizations for WAIHA, 147 (46.9%) received at least one RBC transfusion. In-hospital mortality was higher in the transfused group (4.08%) versus non-transfused (2.41%), but this difference was not statistically significant (p = 0.64); adjusted analysis showed no significant association with mortality (aOR 1.49; 95% CI: 0.28–7.88; p = 0.64). The mean length of stay (LOS) was slightly longer in transfused patients (6.7 vs. 5.8 days; p = 0.16), with adjusted analysis also showing no significant effect on LOS (β = +0.84 days; 95% CI: –0.43 to +2.12; p = 0.20). Mean total hospital charges were higher in transfused patients ($93,600.53 vs. $81,478.87), with an unadjusted difference of $12,121.66 (p = 0.327) that was not statistically significant and an adjusted increase of $20,839.30 trending toward significance (95% CI: –$1,503 to $43,181; p = 0.067). Discharge disposition was similar across groups, with 73.5% discharged home and no significant differences in transfers or facility discharges. No acute transfusion-related complications were observed, supporting the relative safety of RBC transfusion in this population. Conclusion Our study demonstrates that RBC transfusion is common in hospitalized WAIHA patients and is not associated with an increased inpatient mortality. Although transfusion was linked to slightly higher resource use, the low rate of complications supports its safe use when clinically indicated. These findings align with Barros et al.'s systematic review, reinforcing that transfusion in WAIHA—even with panagglutinin presence—can be safely administered and should not be delayed in cases of symptomatic or severe anemia. Transfusion in this setting should be approached confidently rather than with undue caution.