RHD genotyping of serologic RhD‐negative blood donors in a hospital‐based blood donor center

Abstract

BACKGROUND: Serologic RhD-negative blood donors are tested by a method known to detect weak D antigen expression. Serology does not detect all red blood cells with RhD expression and RHD genotyping has been used to identify variant RHD alleles, which may lead to some RhD expression. The aim of this study was to determine the frequency of RHD variant alleles in serologic RhD-negative blood donors at a hospital-based donor center in Los Angeles.STUDY DESIGN AND METHODS: RHD genotyping of serologic RhD-negative blood donors over a 20-month period was performed using the Immucor RHD BeadChip assay. DNA sequencing was performed when the RHD BeadChip assay failed to assign a genotype. For RHD variants known or suspected to result in RhD expression, recipients of previous blood donations were investigated for alloimmunization. RESULTS: RHD genotyping was performed in 1174RhD-negative blood donors, and 1122 were genotyped for RHCE variants. Eleven donors (0.94%) harbored mutations predicted to yield RhD expression. The predicted phenotypes were, in decreasing frequency, DEL, partial, and weak D phenotypes. Anti-D was not detected in 16 patients who had received blood from these donors after an average follow up of 182 days. CONCLUSION:Genotyping can be used to identify donors with the potential to sensitize RhD-negative recipients. In this limited study, 0.94% of serologic RhD-negative blood donors were found to have variant RHD alleles that might cause alloimmunization in RhD-negative recipients. To our knowledge, a study of this nature has not been reported in the United States.From the

Insights intoanti‐Dformation in carriers ofRhDvariants through studies of3Dintraprotein interactions

“…The exploratory analysis of RHD*weak D type 38 showed that the substitution p.G278D did not produce a single difference in intraprotein interactions relative to standard RhD. This result is in favor of the benignity of p.G278D and is consistent with the absence of anti‐D descriptions for a frequent allele, with over 150 samples listed in the literature 8, 46, 55–67 …”

“…This result is in favor of the benignity of p.G278D and is consistent with the absence of anti-D descriptions for a frequent allele, with over 150 samples listed in the literature. 8,46,[55][56][57][58][59][60][61][62][63][64][65][66][67] This study was limited to RhD variants with only one or two amino acid substitutions relative to the wild-type RhD. Many RhD variants associated with anti-D formation have many amino acid substitutions.…”

“…43 In addition, an exploratory analysis of RHD*weak D type 38 was performed. This variant has been described frequently in Brazilians, [55][56][57][58][59][60] in European populations, 46,[61][62][63][64][65][66] and occasionally in Japanese individuals, 67 but no anti-D production has been reported so far. An investigation of the intraprotein interactions of the product of this allele could potentially shed light on the risk of anti-D formation.…”

D variants in the population of D‐negative blood donors in the north‐eastern region of Croatia

“…Many reports have been published on the detection of D variants in order to reduce the residual risk of alloimmunisation to the D antigen 9,17 . To date, many population studies have provided data on RHD molecular background and have shown that the prevalence of D variants varies by races and ethnicity, even within the same country 1,18‐22 . Therefore, each country must conduct its own population study on the prevalence of D variants and adjust typing strategies according to the most prevalent RHD alleles.…”

It's time to phase out “serologic weak D phenotype” and resolve D types with RHD genotyping including weak D type 4

“…We have observed that when the molecular report does not provide an interpretation and recommendation, clinical practictioners not experienced in blood group genetics hesitate to interpret RHD genotyping results as D+ or D−. For the purposes of RhIG adminstration and transfusion, interpretation of an RHD genotype requires not only pertinent experience but also knowledge of the history 2,5 as well as the current evolving data [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] and literature reports 15,16,[23][24][25][26] of the risks for alloimmunization associated with specific RHD genotypes. 27 Hospital computer systems may require updating to accomodate new requirements, such as the ability to change a prior serologic D typing result, when it is overridden by a different D type based on RHD genotyping results.…”