Anti-D Antibodies in Pregnant D Variant Antigen Carriers Initially Typed as RhD+

Abstract

Background: To evaluate the incidence, the consequences, and the prevention strategy of anti-D alloimmunizations of D variant carriers in the obstetric population of Split-Dalmatia County, Croatia. Methods: RhD immunization events were evaluated retrospectively for the period between 1993 and 2012. Women were tested for RhD antigen and irregular antibodies. Those with anti-D antibody who were not serologically D- were genotyped for RHD. They were evaluated for their obstetric and transfusion history and their titer of anti-D. The neonates were evaluated for RhD status, direct antiglobulin test (DAT), hemoglobin and bilirubin levels, transfusion therapy as well as phototherapy and outcome. Results: Out of 104,884 live births 102,982 women were tested for RhD antigen. Anti-D immunization occurred in 184 women which accounts for 0.9% of individuals at risk of anti-D formation. 181 cases occurred in women serologically typed as D-. Three women were partial D carriers (DVa n = 2, DNB n = 1), initially typed RhD+, and recognized as D variant carriers after the immunization occurred. Anti-D titer varied from 1:1 to 1:16. Six children were RhD+, four had positive DAT, and two underwent phototherapy. Conclusion: Anti-D immunization occurred in pregnant partial D carriers (DVa, DNB). RhD+ children had serologic markers of hemolytic disease of the fetus and newborn (HDFN), with no cases of severe HDFN.

Anti‐D reagents should be chosen accordingly to the prevalence of D variants in the obstetric population

“…They did not receive immunoprophylaxis and one of them was transfused with D+ RBC unit. The single case of partial DNB category was detected after the immunization had occurred, similarly as previously reported by other authors . We were therefore unable to determine the prevalence of partial D variant category DNB in our population, because it was typed as D+ due to our reagent selection criteria.…”

Anti‐D in a mother, hemizygous for the variant RHD*DNB gene, associated with hemolytic disease of the fetus and newborn

“…A HDFN case due to anti‐D in a woman carrying the partial D DNB has not been published previously; this case shows it can occur and strengthens the recommendations that women carrying partial D DNB should be offered anti‐D prophylaxis . One case was recently reported by Lukacevic Krstic and coworkers where a newborn from a DNB mother with anti‐D that was barely detectable required phototherapy; however, there was no information in the literature to suggest that 1) anti‐D was eluted from the newborn's RBCs and 2) ABO incompatibility was not ruled out as the cause of HDFN …”

“…Individuals with the partial D, when exposed to RBCs carrying the epitopes they lack, may develop anti‐D . Individuals expressing DNB have been known to produce alloanti‐D with titers ranging up to 128 . This article reports a pregnant woman who groups as D+, carrying the RHD*DNB gene, who was not offered prophylactic anti‐D or D– RBCs and formed alloanti‐D.…”

Frequency and characterization ofRHDvariants in serologically D– Surinamese pregnant women and D– newborns

“…Our study had some limitations: First, our study was performed in D– individuals, while RHD variants are also common in serologically D+ individuals from African descent . In the presence of variants, serologically D+ women may be at risk for anti‐D when pregnant with children carrying wild‐type D antigens . Second, the RH ‐MLPA assay detects most common RHD variants and other (novel) variants may have been missed.…”