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Background: Reduced D antigen on red blood cells (RBCs) may be due to "partial" D phenotypes associated with loss of epitope(s) and risk for alloimmunization or "weak" D phenotypes that do not lack major epitopes with absence of clinical complications. Genotyping of samples with weak and discrepant D typing is recommended to guide transfusion and RhIG prophylaxis. The goal was to compare the impact of RHD genotyping on transfusion practice in two centers serving different populations., Study Design and Methods: Fifty-seven samples from Denmark and 353 from the United States with weak or discrepant D typing were genotyped. RBC typing was by multiple methods and reagents. DNA isolated from white blood cells was tested with RBC-Ready Gene D weak or CDE in Denmark or RHD BeadChip in the United States. RHD was sequenced for those unresolved., Results: Of Caucasian samples from Denmark, 90% (n = 51) had weak D types 1, 2, or 3; two had other weak D, two partial D, and two new alleles. In diverse ethnic U.S. samples, 44% (n = 155) had weak D types 1, 2, or 3 and 56% (n = 198) had other alleles: uncommon weak D (n = 13), weak 4.0 (n = 62), partial D (n = 107), no RHD (n = 9), and new alleles (n = 7)., Conclusion: Most samples with weak or variable D typing from Denmark had alleles without risk for anti-D. In U.S. samples, 48% could safely be treated as D+, 18% may require consideration if pregnancy possible, and 34% could potentially benefit from being treated as D-. Black and multiracial ethnicities were overrepresented relative to population., (© 2020 AABB.)

Background: Reliability of noninvasive prenatal RHD genotype test (NIP RHD) depends on having sufficient amounts of cell-free fetal DNA (cffDNA) in the maternal plasma sample. The fraction of cffDNA in maternal plasma is inversely related to maternal body mass index (BMI), suggesting that high maternal BMI may limit the test's accuracy. This study determined the effect of maternal BMI on the accuracy of NIP RHD., Study Design and Methods: Results from NIP RHD performed in Gestation Week 25 were correlated to maternal BMI in Week 12. The accuracy of NIP RHD result was determined by correlation with serologic RhD types of the neonates., Results: A total of 1618 pregnancies in 1588 D- women were included. Median BMI in these pregnancies was 24.2 (10%-90%, 20.1-32.4), and in 261 of 1618 (16%) pregnancies BMI was 30 or more (median BMI in this group was 33.6; 10th-90th percentiles, 30.5-41.1). NIP RHD was positive in 987 of 1618 (61%), negative in 582 of 1618 (36%), and inconclusive in 49 of 1618 (3.0%). Compared to the neonate's serologic RhD type, nine of 987 (0.9%) positive NIP RHD results were false positive, and four of 582 (0.7%) negative NIP RHD results were false negative (FN). In five of 49 (10%) inconclusive NIP RHD results, the neonatal RhD type was positive. There was no difference in median BMI between individuals who tested inconclusive or FN compared to those with true positive or true negative results (p = 0.80)., Conclusion: The accuracy of NIP RHD testing performed in Gestation Week 25 does not depend on maternal BMI in the 12th gestation week., (© 2018 AABB.)

Background: The RhD antigen is very immunogenic and is a significant cause of hemolytic disease of the newborn (HDN). The RHD-CE(8-9)-D hybrid allele is commonly associated with a D- phenotype. Here, we report a case of high-titer maternal anti-D and late onset of HDN in a newborn carrying a RHD-CE(9)-D variant supposedly encoding the same partial D antigen as the RHD-CE(8-9)-D allele, but with significant expression of D antigen., Study Design and Methods: To elucidate the blood group antigen background of the case, we carried out serologic, flow cytometric, and genetics studies of the newborn and his father., Conclusion: Individuals carrying the RHD-CE(9)-D allele do express D antigen, but do so at significantly lower levels than those carrying the more common D+ phenotypes (e.g., DCe/dce). It may mitigate and delay otherwise severe HDN in pregnancies complicated by high-titer anti-D., (© 2014 AABB.)

Background: A combination of antenatal and postnatal RhD prophylaxis is more effective in reducing D immunization in pregnancy than postnatal RhD prophylaxis alone. Based on the result from antenatal screening for the fetal RHD gene, antenatal RhD prophylaxis in Denmark is given only to those D- women who carry a D+ fetus. We present an evaluation of the first national clinical application of antenatal RHD screening., Study Design and Methods: In each of the five Danish health care regions, blood samples were drawn from D- women in Gestational Week 25. DNA was extracted from the maternal plasma and analyzed for the presence of the RHD gene by real-time polymerase chain reaction targeting two RHD exons. Prediction of the fetal RhD type was compared with serologic typing of the newborn in 2312 pregnancies, which represented the first 6 months of routine analysis., Results: For the detection of fetal RHD, the sensitivity was 99.9%. The accuracy was 96.5%. The recommendation for unnecessary antenatal RhD prophylaxis for women carrying a D- fetus was correctly avoided in 862 cases (37.3%), while 39 women (1.7%) were recommended for antenatal RhD prophylaxis unnecessarily. Two RHD+ fetuses (0.087%) were not detected, and antenatal RhIG was not given., Conclusion: These data represent the first demonstration of the reliability of routine antenatal fetal RHD screening in D-, pregnant women to ascertain the requirement for antenatal RhD prophylaxis. Our findings should encourage the implementation of such screening programs worldwide, to reduce the unnecessary use of RhIG., (© 2011 American Association of Blood Banks.)