Clinical and Immunohematological Significance of Anti-Leᵃ, Anti-Leᵇ, and Anti-E Antibodies in Pre-Transfusion Testing

Background: Unexpected red cell antibodies detected during pretransfusion testing can pose significant challenges in transfusion management, particularly in obstetric patients. While some antibodies are clinically insignificant, others may lead to hemolytic transfusion reactions, necessitating careful immunohematological evaluation. Case Presentation: We report three cases of unexpected red cell antibodies detected during routine pretransfusion testing. In Case 1, a 28-year-old gravida 3 para 1 female with no prior transfusion history showed incompatible crossmatches, and further workup identified an Anti-Leᵇ antibody, with no transfusion required due to minimal blood loss. In Case 2, a 26-year-old primigravida at term with fetal distress demonstrated Anti-Leᵃ antibody during antibody screening. Despite its presence, one unit of PRBC compatible was transfused uneventfully during cesarean section, consistent with the typically clinically insignificant nature of Lewis antibodies. In Case 3, a 46-year-old multiparous female with a history of prior transfusions presented with abnormal uterine bleeding and was found to have anti-E alloantibody. Results: Two cases showed positive direct antiglobulin test (DAT) with negative autocontrol, suggesting alloimmunization. Lewis antibodies (anti-Leᵃ and anti-Leᵇ) were clinically insignificant and did not impact transfusion outcomes, whereas anti-E, a clinically significant Rh antibody, required careful antigen-matched transfusion support. Conclusion: These cases highlight the importance of comprehensive antibody screening and identification in pretransfusion testing. While Lewis system antibodies are usually benign, clinically significant antibodies such as anti-E necessitate antigen-negative blood selection to prevent hemolytic complications. Early detection and appropriate transfusion strategies are essential for ensuring patient safety.