A Rare Case of Delayed Hemolytic Transfusion Reaction Due to Anti-Lea, Anti-Leb, and Anti-M in an Elderly Patient With Choledocholithiasis

Introduction Delayed hemolytic transfusion reactions (DHTRs) are rare but potentially severe immune-mediated complications that typically occur days after red cell transfusion. Although antibodies such as anti-Lea, anti-Leb, and anti-M are commonly considered clinically insignificant due to their cold-reactive nature, these antibodies may trigger significant hemolysis under certain conditions. Method An 89-year-old male with choledocholithiasis developed DHTR following administration of multiple units of packed red blood cells. Initial antibody screening yielded negative results. Upon clinical deterioration, serologic evaluations were performed using conventional tube methods and column agglutination testing. Direct and indirect antiglobulin tests, antibody identification panels, and extended red cell antigen typing were conducted. Results Subsequent testing revealed a positive direct antiglobulin test (2+), elevated lactate dehydrogenase (LDH), progressive hemoglobin decline (from 11.8 to 5.8 g/dL), and acute kidney injury. Antibody identification confirmed the presence of anti-Lea, anti-Leb, and anti-M antibodies. Transfused units were found to be antigen positive for these antibodies. Clinical improvement followed cessation of incompatible transfusions and initiation of supportive care. The case also highlighted variation in antibody detection sensitivity between testing methods, particularly the limitations of column agglutination alone. Conclusion This case illustrates the critical need to recognize the potential clinical significance of antibodies traditionally classified as insignificant, especially in elderly or multi-transfused patients. Extended antigen typing and the use of sensitive detection methods are essential for improving transfusion safety and preventing delayed immune complications.