Patients with Asian-type DEL can safely be transfused using RhD-positive blood

Background and ObjectivesSerologic typing with monoclonal anti‐D is mandatory for RHD antigen determination before transfusion, but due to aberrant (weak or partial) variants of RHD, results may be ambiguous and molecular RHD‐typing is required. Before that, RHD‐negative (RHD –) red blood cells concentrates (RBCs) shall be transfused to avoid anti‐D formation, which probably leads to wastage of RHD ‐ RBCs.Study Design and MethodsAll patients with ambiguous results in serologic RHD‐typing and molecular RHD‐typing were assessed retrospectively. The proportions of patients at risk for anti‐D formation and the proportion of RHD ‐ RBCs transfused unnecessarily were evaluated for the following transfusion strategies: (1) RHD‐positive (RHD + )RBCs for all patients, (2) RHD + RBCs for patients with at least 2+ reaction with anti‐D, (3) RHD + RBCs for patients with C and/or E in their RHCE‐phenotype, (4) RHD + RBCs for patients with C and/or E and at least 2+ reaction, and (5) RHD ‐ RBCs for all patients.ResultsA total of 112 patients were included. Most had weak D type 1–3 and a minority had other, rare RHD variants. The risk of anti‐D formation was 4.5%, 2.9%, 1.8%, 1.0%, and 0% for strategies 1–5, respectively. The proportion of RHD ‐ RBCs transfused unnecessarily was 0%, 49.5%, 0.9%, 50.5%, and 95.5%.ConclusionTransfusing patients with a C and/or E in their RHCE‐phenotype with RHD + RBCs resulted in a very low risk of immunization while avoiding wastage of RHD ‐ RBCs. Therefore, this strategy should be used for some patients with ambiguous results in serologic RHD‐typing and pending results of molecular RHD‐typing.

Section: Discussionmentioning

confidence: 99%

RHD‐negative red cells may be avoided for patients with ambiguous serologic typing for the RHD antigen

Juhl,

Luckner,

Brockmann

et al. 2023

“…29 RHD(1227G>A) expresses a very weak D antigen with the complete repertoire of D antigen epitopes, which indicates that Asian-type DEL recipients may not develop alloanti-D after exposure to RhD-positive RBCs. 12 Although some retrospective studies indicated that no alloantibodies against RBC antigens were identified in cases of pregnancy with RHD(1227G>A), [30][31][32] those women are routinely managed as RHD*01N.01 individuals in most Chinese hospitals. Takahashi et al 16 explored an RHD genotyping method based on amplicon-sequencing and correctly predicted fetal RHD genotyping for eight RhD-negative pregnant women, including three pregnant women carrying RHD (1227G>A).…”

Section: Discussionmentioning

confidence: 99%

Noninvasive screening of fetal RHD genotype in Chinese pregnant women with serologic RhD‐negative phenotype

Duan,

Li,

Jiang

et al. 2023

BackgroundNoninvasive fetal RHD genotyping has been provided to nonimmunized RhD‐negative pregnant women to guide anti‐D prophylaxis. Among the Chinese, more than 30% of the RhD‐negative phenotype is associated with variant RHD alleles, which would limit the accuracy of fetal RHD status prediction; thus, more targeting and proper programs need to be developed.Study Design and MethodsFluorescence quantitative polymerase chain reaction PCR (qPCR) or Sanger sequencing on all RHD exons was used to detect maternal RHD genotypes. For pregnant women with RHD*01N.01 or RHD*01N.03 alleles, the presence of RHD exons 5 and 10 in cell‐free DNA was determined by qPCR. For pregnant women with the RHD(1227G>A) allele, high‐throughput sequencing on exon 9 of the RHD gene and RHCE gene was used to predict fetal RhD phenotype.ResultsAmong 65 cases of Chinese pregnant women with the serologic RhD‐negative phenotype, three major genotypes were identified: RHD*01N.01/RHD*01N.01 (61.5%), RHD*01N.01/RHD(1227G>A) or RHD*01N.03/RHD(1227G>A) (20%), and RHD*01N.01/RHD*01N.03 (13.8%), along with three cases of minor genotypes (4.6%). For 43 pregnant women with the RHD*01N.01 or RHD*01N.03 alleles, qPCR on maternal cell‐free DNA yielded a 98.5% (42/43) accuracy rate and 100% successful prediction rate. High‐throughput sequencing was successfully used to predict fetal RhD phenotypes for 13 pregnant women with RHD(1227G>A).ConclusionOn the basis of maternal RHD genotyping, fetal genotyping through qPCR or high‐throughput sequencing can improve the accuracy and success rate of prenatal fetal RhD phenotype prediction among Chinese pregnant women. It plays a potential role in guiding anti‐D prophylaxis and pregnancy management in Chinese pregnant women.

“…And based on the resolution of the molecular structure, it was predicted early on that Asian‐type DEL recipients “might not even develop anti‐D after exposure to regular” RhD‐positive red cells. “Because of the sheer number of patients and of blood units involved, this topic could considerably affect—and might ease—transfusion practice in East Asian populations.” 17 These predictions have since been confirmed by many studies and their clinical advantages are now becoming widely implemented in clinical practice for Asian‐type DEL 14 . In contrast, some other DEL variants are categorized as partial and lack one or more D‐epitopes, making them prone to develop anti‐D if exposed to regular RhD‐positive red cells 6,8 …”

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confidence: 93%

“…17 These predictions have since been confirmed by many studies and their clinical advantages are now becoming widely implemented in clinical practice for Asian-type DEL. 14 In contrast, some other DEL variants are categorized as partial and lack one or more D-epitopes, making them prone to develop anti-D if exposed to regular RhDpositive red cells. 6,8 Various HLA alleles have been reported to increase or decrease red cell alloimmunization.…”

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confidence: 99%

“…6 The most common DEL variant is designated as the "Asian-type" DEL (RHD*DEL1, or RHD:c.1227G > A) 5,[11][12][13] and has been shown to harbor a complete set of D-epitopes. 6 For this reason, no anti-D immunization seemed to have occurred in individuals with the Asian-type DEL, 14 despite multiple reports in DEL patients. It has been recommended that patients, pregnant women, and donors with the Asian-type DEL are managed as RhD-positive.…”

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confidence: 99%

See 1 more Smart Citation

Asian‐type DEL (RHDDEL1*) with an allo‐anti‐D: A paradoxical observation in a healthy multiparous woman

Ohto

Srivastava

et al. 2023

BackgroundThe DEL phenotype is the D variant expressing the least amounts of D antigen per red cell. Asian‐type DEL (RHD:c:1227G > A) is the most prevalent DEL in East Asia without any anti‐D alloimmunization reported before. We investigated the first observation of an anti‐D in any DEL phenotype, reported in the Japanese language at a 1987 conference, only 3 years after the discovery of DEL.MethodsWe contacted the proband 35 years after the initial report. Standard hemagglutination, adsorption/elution, and flow cytometry tests were performed, as was nucleotide sequencing for the RHD, RHCE, and HLA class I and class II genes.ResultsThe healthy multiparous Japanese woman, a regular blood donor, still had the anti‐D of titer 8 representing an alloantibody by standard serologic methods. Unexpectedly, she carried an Asian‐type DEL without any additional RHD gene variation. All 12 HLA alleles identified were known in the Japanese population. Interestingly, one of her HLA‐DRB1 and a variant of her HLA‐DQB1 alleles had previously been associated with anti‐D immunization.ConclusionWe described an allo‐anti‐D, maintained for more than three decades, in an Asian‐type DEL. The combination of two implicated HLA alleles were rare and could have contributed to the anti‐D immunization. Continued monitoring of anti‐D immunization events in patients with DEL is warranted, and we discuss possible mechanisms for further study. As only this single observation has been recognized in the last 35 years, the current recommendation is affirmed: Individuals with Asian‐type DEL should be treated as Rh D‐positive for transfusion and Rh immune prophylaxis purposes.