Fetal inheritance of GP*Mur causing severe HDFN in an unrecognized case of maternal alloimmunization

Abstract

BACKGROUND The clinical and laboratory features of hemolytic disease of the newborn can be challenging to diagnose during pregnancy in the apparent absence of a blood group antibody. Low‐frequency antibodies go undetected due to the lack of appropriate antigen‐positive reagent red blood cells (RBCs). CASE REPORT A pregnant woman of Southeast Asian descent was referred to a maternal‐fetal medicine outpatient clinic due to a complicated obstetric history and a negative antibody screen. This initial visit at 29 weeks and 0 days’ gestational age (GA) was unremarkable. A hydropic infant, born at 29 weeks and 5 days’ GA, succumbed on the seventh day of life. Comprehensive laboratory testing was performed after birth. The hospital blood bank performed a maternal antibody identification. Direct antiglobulin test was performed on the cord blood. A reference laboratory confirmed an anti‐Mia, performed paternal Mia phenotyping, and identified a hybrid glycophorin B‐A‐B GP*Mur allele. DISCUSSION Maternal alloimmunization to low‐frequency antigens remains a challenge. Southeast Asians make up a significant percentage in some US locations. Worldwide reports on the frequency of maternal alloimmunization of the MNS system can be used to guide the use of specific reagent RBCs for testing. Such strategies rely on the identification of blood donor units for reagent manufacture and use in perinatal antibody screens. CONCLUSION The incidence of Mia and related antibodies is significant among Southeast Asians. In North America, prenatal antibody screening cells are not routinely chosen to match this population. The clinical and societal implications are discussed.

Low prevalence red blood cell antigens: transfusions, babies, and changing demographics

“…Future efforts may result in the ready availability of US antibody screening reagents tailored to detection of antibodies found in locally prevalent ethnic groups. As advocated by Mallari,6 this is the ideal solution. At present, the increased demand for the appropriate antigen-positive RBCs may not be commercially viable or sustainable even with increased screening protocols.…”

“…Reagent RBCs based on FDA and JPAC requirements are used in areas where antigens typically of low prevalence in the European population occur at higher prevalence rates, either widely or within subpopulations. Mallari and colleagues 6 reviewed the antigens created on hybrid glycophorin A and glycophorin B variants in the MNS system. The antigens Mi a and Mur are found singly or together on seven of the 21 reported glycophorin hybrids, 7 GP.Mur being the most common.…”

“…Yet global migration and immigration are changing the discussion of which LPA antigens and associated antibodies may be encountered in the donor and patient populations. Mallari et al 6 present compelling information on how the increasing Asian populations in areas of the western United States may be expected to impact the incidence of Mi a and other antigens found on MNS glycophorin hybrids. Based on analysis of 2018 Census Bureau estimates, Hispanics and Asians were the fastest-growing minority groups in the United States between 2010 and 2018 with increases of 18.3% and 27.4%, respectively.…”

“…Are unrecognized antibodies to LPA more significant in the setting of pregnancy and possible HDFN? In this issue of TRANSFUSION, Mallari and colleagues describe a case of severe HDFN caused by anti‐Mi a resulting in postnatal fetal demise. The striking feature of this report is that the proposita resides in the United States, where anti‐Mi a is infrequently encountered but with population centers where the antigen is likely of higher prevalence.…”

Universal Detection of Mia Antigen and Frequencies of Glycophorin Hybrids among Blood Donors in Taiwan by Human Monoclonal Antibodies against Mia (MNS7), Mur (MNS10), and MUT (MNS35) Antigens

“…These antibodies are a combination of several specificities or monospecific specificity, such as anti-Vw + Hut + Mur + Mut + Hil or anti-Mur only [ 6 , 17 ]. Alloantibodies, such as anti-Mi a , anti-Mur, anti-Hut, and anti-Vw, cause hemolytic disease of the fetus and newborn and delayed hemolytic transfusion reactions [ 18 , 19 , 20 , 21 ]. Patients with these antibodies need to be transfused with RBC negative for the corresponding antigens [ 14 ].…”