Red blood cell alloimmunization and minor red blood cell antigen phenotypes in transfused Ghanaian patients with sickle cell disease.

BACKGROUND: The routine pretransfusion investigations in Southern Ghana involve only ABO-D blood group typing and ABO compatibility testing without screening for irregular red blood cell (RBC) antibodies. The prevalence and specificities of RBC antibodies and frequencies of most minor blood group antigens in transfused patients with sickle cell disease (SCD) in Ghana are not known and are the objectives of this study. STUDY DESIGN AND METHODS: This was a cross-sectional study that investigated transfused patients with SCD for the presence of irregular RBC antibodies and Rhesus, Kell, Duffy, Kidd, and Ss antigens. RESULTS: From a total of 154 patients (median age, 9 years), 10 patients (6.5%) possessed 13 antibodies, predominantly against D, C, and E antigens. In three patients, the antibodies (anti-D, anti-D + C, and anti-C + e) were against antigens they possessed by serology. Genotyping showed that two of these patients had variant RHCE genes that encode for weak and partial e antigens and one patient had a partial RHC gene. Frequencies of most RBC antigens were comparable with frequencies established among the African American population; however, K-k- and Jk(a-b-) phenotypes were more frequent and were present in 21% and 17% of patients, respectively. CONCLUSION: The prevalence of RBC alloimmunization in transfused Ghanaian patients with SCD was 6.5% and the majority of antibodies were against antigens of the Rh system. Our findings stress the need to include pretransfusion testing for RBC antibodies in patients with SCD, to improve transfusion safety.

Development of red blood cell autoantibodies following treatment with checkpoint inhibitors: a new class of anti-neoplastic, immunotherapeutic agents associated with immune dysregulation.

CONCLUSIONS: Ipilimumab, nivolumab, and pembrolizumab represent a new class of immunotherapeutic drugs for treating patients with advanced cancer. Known as checkpoint inhibitors, these drugs act to upregulate the cellular and humoral immune response to tumor antigens by inhibiting T-cell autoregulation. As a consequence, they can be associated with immune-related adverse events (irAEs) due to loss of self-tolerance, including rare cases of immune-related cytopenias. We performed a retrospective clinical chart review, including serologic, hematology, and chemistry laboratory results, of two patients who developed red blood cell (RBC) autoantibodies during treatment with a checkpoint inhibitor. Serologic testing of blood samples from these patients during induction therapy with ipilimumab and nivolumab, respectively, showed their RBCs to be positive by the direct antiglobulin test (IgG+, C3+) and their plasma to contain panreactive RBC autoantibodies. Neither patient had evidence of hemolysis. Both patients developed an additional irAE during treatment. A literature review for patients who had developed immune-mediated cytopenia following treatment with a checkpoint inhibitor was performed. Nine other patients were reported with a hematologic irAE, including six with anemia attributable to autoimmune anemia, aplastic anemia, or pure RBC aplasia. Hematologic irAEs tend to occur early during induction therapy, often coincident with irAEs of other organs. In conclusion, checkpoint inhibitors can be associated with the development of autoantibodies, immune-mediated cytopenias, pure RBC aplasia, and aplastic anemia. Immunohematology reference laboratories should be aware of these agents when evaluating patients with advanced cancer and new-onset autoantibodies, anemia, and other cytopenias.