The first case of severe acute hemolytic transfusion reaction caused by anti‐Sc2

Abstract

BACKGROUND Alloantibodies to the low‐frequency antigen Scianna‐2 (Sc2) have been implicated in cases of hemolytic disease of the fetus and newborn but never in hemolytic transfusion reactions (HTRs); thus, the clinical significance of anti‐Sc2 has yet to be fully addressed. STUDY DESIGN AND METHODS A 26‐year‐old woman with thalassemia presented rigors, fever, nausea, abdominal pain, and hemolytic biochemistry after exposure to 75 mL of plasma‐reduced red blood cells (RBCs). The RBC unit was issued by electronic crossmatch but was 3+ incompatible on recrossmatch by gel indirect antiglobulin test (IAT). The patient had anti‐Sc2 previously identified, but considered to be clinically insignificant. The transfusion history was reviewed and a monocyte monolayer assay (MMA) was performed. RESULTS The patient was investigated for a RBC reaction 9 years prior, when she developed symptoms of HTR. The RBC unit was crossmatched by immediate spin due to consistent screen negativity. Full crossmatch found the RBC 1+ incompatible by gel IAT with both pre/post samples, while direct antiglobulin test was negative (pre) and 1+ immunoglobulin G positive (post). The antibody remained unidentified and she was committed to gel IAT crossmatch. Two‐years later, the specificity to Sc2 was deduced when one RBC unit was found 3+ incompatible. Finally, the transfusion reaction reported herein occurred when she received by happenstance RBCs from the same donor who was associated with the remote reaction 9 years earlier. MMA yielded highly positive phagocytic indices only for Sc2+ RBCs, including the donor's RBCs that triggered the severe HTR. CONCLUSION This is the first case of HTR caused by anti‐Sc2 confirmed by clinical findings and MMA.

SCAR: The high‐prevalence antigen 013.008 in the Scianna blood group system

“…Other alloantibodies to high‐prevalence Scianna antigens, such as Sc3 21,44–46 and SCAN, 21 have been documented to be clinically relevant 7,13 . Using autologous monocytes in an MMA has recently corroborated the clinical relevance of alloanti‐Sc2 in a patient with severe hemolytic transfusion reaction 20 . Alloanti‐Sc4 has also been known to cause HDFN 18 .…”

“…The low titer of anti‐SCAR in the patient (Table 3) may have prevented an obvious transfusion reaction at that time. Also, the MMA used allogeneic monocytes, which may not have closely replicated the immune status and Fc‐receptor polymorphisms of the patientʼs monocytes 20 . However, the occurrence of anti‐SCAR had a clinical consequence, because the patient was transitioned to hydroxyurea to prevent any boosting of the anti‐SCAR titer through continued SCAR+ red cell transfusions, which might eventually have resulted in a transfusion reaction.…”

“…Allogeneic peripheral blood mononuclear cells were incubated in chamber slides for 1 hour at 37°C, as previously described. 20,30 Red cells sensitized in vitro with patientʼs plasma were layered onto the monocyte monolayer and incubated for 1 hour at 37°C. The slides were rinsed to remove non-adherent red cells and the monocytes were stained.…”

“…SC antibodies to high‐prevalence antigens, particularly Sc1, and also Sc3, Sc5, Sc6, and Sc7, can mask other antibodies, when inhibition using soluble protein is possible and helpful 15,16 . Previous reports suggest alloantibodies to Sc2 17 and Sc4 18 are associated with severe hemolytic disease of the fetus and newborn (HDFN) and some with acute hemolytic 19,20 or delayed hemolytic or serologic transfusion reactions 3,7,13,21 . Autoantibodies binding to the SC protein have been reported in patients with clinically relevant autoimmune hemolytic anemia 7,19,22–25 …”

Serologic assessments in acute transfusion reactions: practices and yields

“…However, all findings in the complicated allergic reactions (involving three recipients) and in the ‘other’ category (involving nine recipients) solely reflected acquired ABO isohaemagglutinins rather than host‐derived antibodies. After subtracting isohaemagglutinins, the rank order for informative (non‐isohaemagglutinin) discoveries was owing to a patient with high‐risk fever (one case, targeting Sc2) and a reaction with both high‐risk fever and cardiorespiratory features (one case, targeting AnWj, in its first recognition).…”