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Transfusion strategy for weak D Type 4.0 based on RHD alleles and RH haplotypes in Tunisia.

ABSTRACT: BACKGROUND:With more than 460 RHD alleles, this gene is the most complex and polymorphic among all blood group systems. The Tunisian population has the largest known prevalence of weak D Type 4.0 alleles, occurring in one of 105 RH haplotypes. We aimed to establish a rationale for the transfusion strategy of weak D Type 4.0 in Tunisia. STUDY DESIGN AND METHODS:Donors were randomly screened for the serologic weak D phenotype. The RHD coding sequence and parts of the introns were sequenced. To establish the RH haplotype, the RHCE gene was tested for characteristic single-nucleotide positions. RESULTS:We determined all RHD alleles and the RH haplotypes coding for the serologic weak D phenotype among 13,431 Tunisian donations. A serologic weak D phenotype was found in 67 individuals (0.50%). Among them, 60 carried a weak D Type 4 allele: 53 weak D Type 4.0, six weak D Type 4.2.2 (DAR), and one weak D Type 4.1. An additional four donors had one variant allele each: DVII, weak D Type 1, weak D Type 3, and weak D type 100, while three donors showed a normal RHD sequence. The weak D Type 4.0 was most often linked to RHCE*ceVS.04.01, weak D Type 4.2.2 to RHCE*ceAR, and weak D Type 4.1 to RHCE*ceVS.02, while the other RHD alleles were linked to one of the common RHCE alleles. CONCLUSIONS:Among the weak D phenotypes in Tunisia, no novel RHD allele was found and almost 90% were caused by alleles of the weak D Type 4 cluster, of which 88% represented the weak D Type 4.0 allele. Based on established RH haplotypes for variant RHD and RHCE alleles and the lack of adverse clinical reports, we recommend D+ transfusions for patients with weak D Type 4.0 in Tunisia.

SUBMITTER: Ouchari M

PROVIDER: S-EPMC5803429 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Transfusion strategy for weak D Type 4.0 based on RHD alleles and RH haplotypes in Tunisia.

Ouchari Mouna M Srivastava Kshitij K Romdhane Houda H Jemni Yacoub Saloua S Flegel Willy Albert WA

Transfusion 20171129 2

<h4>Background</h4>With more than 460 RHD alleles, this gene is the most complex and polymorphic among all blood group systems. The Tunisian population has the largest known prevalence of weak D Type 4.0 alleles, occurring in one of 105 RH haplotypes. We aimed to establish a rationale for the transfusion strategy of weak D Type 4.0 in Tunisia.<h4>Study design and methods</h4>Donors were randomly screened for the serologic weak D phenotype. The RHD coding sequence and parts of the introns were se ...[more]

PMID: 29193104

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Project description:D- red blood cells (RBCs), always in short supply, and Rh immune globulin (RhIG) are not needed for patient care if D+ RBCs can safely be transfused. According to a recent work group recommendation, patients with the RHD*weak D type 4.0 allele can be considered D+. We report an African American woman who presented for delivery at the end of the third trimester, at which time anti-U and a serologic weak D phenotype were recognized, requiring U-, D- RBC units. We obtained 3 U- RBC units, including 1 D- unit. Later, the RHD*weak D type 4.0 allele was determined by RHD genotyping, only 6 days before delivery. The patient had an uneventful vaginal delivery of a D+ baby. No transfusion was needed for mother or baby. In this case, a pregnant woman with the RHD*weak D type 4.0 allele can safely be managed as D+, relaxing the unnecessary D- restriction for the limited U- RBC supply. The procured U-, D- RBC unit was frozen with 14 days of shelf-life remaining. To conserve D- RBC units, not limited to U-, for patients with a definite need, we recommend molecular analysis of a serologic weak D phenotype before a transfusion becomes imminent. The best time to resolve a serologic weak D phenotype with RHD genotyping is early in a pregnancy. Immunohematology 2021;37:1-4 .D– red blood cells (RBCs), always in short supply, and Rh immune globulin (RhIG) are not needed for patient care if D+ RBCs can safely be transfused. According to a recent work group recommendation, patients with the RHD*weak D type 4.0 allele can be considered D+. We report an African American woman who presented for delivery at the end of the third trimester, at which time anti-U and a serologic weak D phenotype were recognized, requiring U–, D– RBC units. We obtained 3 U– RBC units, including 1 D– unit. Later, the RHD*weak D type 4.0 allele was determined by RHD genotyping, only 6 days before delivery. The patient had an uneventful vaginal delivery of a D+ baby. No transfusion was needed for mother or baby. In this case, a pregnant woman with the RHD*weak D type 4.0 allele can safely be managed as D+, relaxing the unnecessary D– restriction for the limited U– RBC supply. The procured U–, D– RBC unit was frozen with 14 days of shelf-life remaining. To conserve D– RBC units, not limited to U–, for patients with a definite need, we recommend molecular analysis of a serologic weak D phenotype before a transfusion becomes imminent. The best time to resolve a serologic weak D phenotype with RHD genotyping is early in a pregnancy. Immunohematology 2021;37:1–4 .

Project description:BackgroundRed cell (RBC) blood group alloimmunization remains a major problem in transfusion medicine. Patients with sickle cell disease (SCD) are at particularly high risk for developing alloantibodies to RBC antigens compared to other multiply transfused patient populations. Hemagglutination is the classical method used to test for blood group antigens, but depending on the typing methods and reagents used may result in discrepancies that preclude interpretation based on serologic reactivity alone. Molecular methods, including customized DNA microarrays, are increasingly used to complement serologic methods in predicting blood type. The purpose of this study was to determine the diversity and frequency of RH alleles in African Americans and to assess the performance of a DNA microarray for RH allele determination.Material and methodsTwo sets of samples were tested: (i) individuals with known variant Rh types and (ii) randomly selected African American donors and patients with SCD. Standard hemagglutination tests were used to establish the Rh phenotype, and cDNA- and gDNA-based analyses (sequencing, PCR-RFLP, and customized RHD and RHCE microarrays were used to predict the genotype).ResultsIn a total of 829 samples (1658 alleles), 72 different alleles (40 RHD and 32 RHCE) were identified, 22 of which are novel. DNA microarrays detected all nucleotides probed, allowing for characterization of over 900 alleles.ConclusionsHigh-throughput DNA testing platforms provide a means to test a relatively large number of donors and potentially prevent immunization by changing the way antigen-negative blood is provided to patients. Because of the high RH allelic diversity found in the African American population, determination of an accurate Rh phenotype often requires DNA testing, in conjunction with serologic testing. Allele-specific microarrays offer a means to perform high-throughput donor Rh typing and serve as a valuable adjunct to serologic methods to predict Rh type. Because DNA microarrays test for only a fixed panel of allelic polymorphisms and cannot determine haplotype phase, alternative methods such as Next Generation Sequencing hold the greatest potential to accurately characterize blood group phenotypes and ameliorate the clinical course of multiply-transfused patients with sickle cell disease.

Dataset Information

Transfusion strategy for weak D Type 4.0 based on RHD alleles and RH haplotypes in Tunisia.

Publications

Transfusion strategy for weak D Type 4.0 based on RHD alleles and RH haplotypes in Tunisia.

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