Hemolytic disease of the fetus and newborn mediated by anti-Di^a in a U.S. hospital

Di^a is one of the most clinically significant low-prevalence antigens in the Diego blood group system, since antibodies to Di^a have, albeit rarely, been implicated in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn (HDFN). Given the geographical association, most anti-Di^a HDFN cases have been reported in Japan, China, and Poland. We describe a case of HDFN in a neonate born to a 36-year-old G4P2012 woman of self-identified Hispanic ethnicity and of South American descent with multiple negative antibody detection tests in a U.S. hospital. Upon delivery, a cord blood direct antiglobulin test was positive (3+ reactivity), and neonatal bilirubin levels were moderately elevated, but phototherapy and transfusion were not required. This case highlights a rare, unexpected cause of HDFN in the United States secondary to anti-Di^a, given the near-universal absence of this antigen and antibody in most U.S. patient populations. The case also demonstrates the need for awareness of antibodies to antigens that are considered “low-prevalence” in most populations but that might be encountered more frequently in specific racial or ethnic groups and may require more extensive testing.