Financial implications of RHD genotyping of pregnant women with a serologic weak D phenotype.

In the United States, rates of hemolytic disease of the fetus and newborn (HDFN) have declined dramatically since the introduction of Rh immunoprophylaxis to prevent maternal–fetal alloimmunization.1,2 HDFN is caused by the transplacental passage of maternal IgG alloantibodies directed against fetal blood group antigens3 and classically involves incompatibility of the Rh blood group D (RhD) antigen.4 Fetomaternal hemorrhage in a D− pregnant female with a D+ fetus can induce production of anti-D, leading to potentially severe HDFN and possible fetal death during current or future pregnancies.3 The American College of Obstetrics and Gynecology recommends antenatal and postpartum use of RhIG for D− pregnant females with D+ fetuses.4 D− females requiring transfusion are also only provided with D− red blood cells (RBCs). RhD alloimmunization during pregnancy has declined dramatically and now occurs in approximately six of every 1000 live births.2 While guidelines for administration of RhIG to D− women are clear, prophylactic practices for pregnant women who have serologic weak D phenotypes vary. A serologic weak D phenotype is defined as absent or weak (<2+) reactivity of RBCs with an anti-D reagent in initial testing, but moderate to strong agglutination with addition of antihuman globulin (weak D test), if performed. In the United States, a small minority of individuals have an altered RHD gene, which encodes expression of D antigen that may type as weaker than expected, depending on the method and reagent used for detection.5-9 While a 2006 American College of Obstetrics and Gynecology recommendation states that women with weak D phenotypes should be considered D+ and not be given RhIG,4 AABB (formerly known as American Association of Blood Banks) Standards state that “the test for weak D is unnecessary when testing the patient,” thereby encouraging the conservative management of these women as D−.10 A 2012 survey from the College of American Pathologists demonstrated a lack of consistent practices for the management of pregnant women with serologic weak D phenotypes.11 Developing standard practices for the management of these individuals has implications for patient health as well as financial consequences. Further complicating the design of an appropriate management strategy for individuals with serologic weak D phenotypes is the extensive genetic variability in RHD alleles associated with this phenotype, since only certain alleles are associated with any risk of D alloimmunization. A recently convened AABB and College of American Pathologists work group concluded that individuals with serologic weak D phenotypes associated with alleles that encode weak D Types 1, 2, or 3 could be safely managed as D+ and has proposed incorporating RHD genotyping in the management of pregnant women presenting with D typing discrepancies.12 In this analysis, we evaluated the financial implications of using RHD genotyping to guide the management of pregnant females identified as having serologic weak D phenotypes. We modeled a dynamic US population undergoing pregnancies, births, and deaths, tracking pregnancy-related costs and events. The model also incorporated race and ethnicity-dependent probabilities of alternative RHD genotypes to realistically estimate financial impact across the entire US population.