BackgroundPacked red blood cell (PRBC) transfusion is critical in managing pediatric patients with conditions requiring frequent transfusions, such as leukemia, thalassemia, and bone marrow disorders. Alloimmunization, the formation of antibodies against foreign antigens in donor blood, is a significant complication of repeated transfusions. Further, auto/alloimmunization is influenced by multiple factors, including antigenic differences between donor and recipient and the recipient’s immune status. ObjectivesThis study aimed to assess the prevalence and risk factors of auto/alloimmunization among pediatric patients requiring multiple PRBC transfusions in a tertiary care hospital in the sub-Himalayan region of Uttarakhand, India. MethodsA cross-sectional study was conducted on multiply transfused 113 pediatric patients aged 4 months to 18 years who received more than one PRBC transfusion between September 2022 and August 2023. Antibody screening and identification were performed using column agglutination techniques. Statistical analysis was conducted to evaluate associations between demographic, clinical factors, and antibody detection. ResultsAlloimmunization was observed in 5.31% of patients, with the majority developing antibodies against the MNS blood group system. Autoantibodies were more common, detected in 17.7% of patients. Significant associations were found between the history of prior PRBC transfusions and the presence of alloantibodies (p=0.005). Age, gender, and ethnicity did not show a statistically significant association with antibody detection. ConclusionsThe study reveals a relatively higher prevalence of autoimmunization among multi-transfused pediatric patients. The history of PRBC transfusions was a significant risk factor, indicating the need for extended RBC phenotyping and tailored transfusion strategies to reduce alloimmunization risks in these patients. Most patients and blood donors in this region belong to the local Garhwali community. This homogeneity may help explain the lower rate of alloimmunization observed, suggesting a degree of antigenic similarity among the blood donors and the recipients.