Clinical Relevance of Anti-S and Anti-M Antibodies in Crossmatch Incompatibility: A Case Series

Background: Alloimmunization is a challenge in transfusion medicine, especially among patients with prior transfusions or pregnancies. Crossmatch incompatibility from unexpected red cell antibodies can delay transfusions, impact outcomes, and cause hemolysis.Aim: To highlight the clinical significance of anti-S and anti-M antibodies of the MNS system in crossmatch incompatibility, by summarizing six cases managed in our department.Methods: We present a retrospective case series of six patients exhibiting serologic incompatibility during pre-transfusion testing between May 2024 and May 2025 at a tertiary care center. Antibody screening and identification were conducted using column agglutination technology (CAT, Ortho vision) with 3-cell and 11-cell commercial panels. Quality control was ensured according to manufacturer protocols. Compatible and incompatible units were recorded using standardized grading and QC systems.Results: Among 55,542 crossmatched patients, six (all females; mean age 36 years; range 11–53) showed crossmatch incompatibility owing to Anti-S (4/6) or Anti-M (2/6) antibodies. Most had prior transfusion or pregnancy history. Anti-M was reactive at 37°C/AHG phase in both cases. Compatible units were identified and transfused as indicated; overall, 51 units were crossmatched (29 incompatible, 22 compatible, see Table 1). Four patients were transfused uneventfully with compatible antigen-negative units.Conclusion: Early identification of clinically significant red cell antibodies and provision of antigen-negative blood are crucial for safe transfusion. Anti-S and Anti-M antibodies, although uncommon, should be considered during incompatibility evaluation, particularly in settings with high transfusion exposure or pregnancy rates.