The second reported case of a hemolytic transfusion reaction caused by anti-Sc2: a clinical diagnosis

SC2 is a low-prevalence antigen of the Scianna blood group system, historically associated with hemolytic disease of the fetus and newborn and only one prior case of hemolytic transfusion reaction (HTR). We report a second case of anti-Sc2-mediated HTR in a 33-year-old woman with β-thalassemia major and a history of anti-Sc2. She presented for routine transfusion and received 1 group O, D-E-K-S-Jk(a-) red blood cell (RBC) unit that was crossmatch compatible by the antihuman globulin (AHG)-polyethylene glycol testing method. Shortly after the transfusion, she developed chills and back pain that resolved with meperidine. Several hours later, she experienced jaundice, dark urine, and fatigue. Laboratory evaluation revealed a hemoglobin drop below the pre-transfusion baseline, elevated bilirubin (8.0 mg/dL, reference range ≤1.2 mg/dL), and a 2+ incompatibility between the post-transfusion sample and the donor RBC unit segment. Although the direct antiglobulin test and the antibody screen remained negative, reference testing confirmed anti-Sc2 in the post-transfusion plasma, and the donor RBC unit was Sc2+. This case reinforces the clinical relevance of anti-Sc2, highlights limitations of conventional antibody screening and the AHG crossmatch in detecting low-prevalence antigens, and supports the need for heightened clinical suspicion and individualized transfusion strategies, including additional targeted pre-transf usion testing, early consultation with reference laboratories, and sourcing of antigen-negative units in patients with known rare alloantibodies.