Nonsurgical bleeding diathesis in anemic thrombocytopenic patients

Abstract

The identification of 12 novel RHD alleles represents a significant addition to the known repertoire of unusual RHD variants and, at the same time, serves to deepen our understanding of the molecular basis of weak and partial D. The accurate molecular typing of RHD alleles would allow to reduce the alloimmunization risk.

Variant screening of the RHD gene in a large cohort of subjects with D phenotype ambiguity: report of 17 novel rare alleles

“…Using a previously established approach, 10 we systematically screened the RHD coding sequences as well as the exon‐intron boundaries in 806 subjects with doubtful D phenotypes and found DNA variants in 755 samples, with a variant detection frequency of 93.7%. In particular, this effort resulted in the identification of 10 novel single‐nucleotide substitutions (Table 1) and seven novel complex alleles (Table 2).…”

“…Although direct sequencing is currently the gold standard in mutation identification, it is still relatively laborious and expensive. To circumvent these limitations, we established a DHPLC‐based screening assay that enabled us to retrospectively identify 12 novel RHD alleles in 2007 10 . Here, using the same method, we prospectively analyzed a large cohort of samples with doubtful D phenotypes and identified further novel RHD alleles.…”

“…Genomic DNA was extracted from a 2‐mL blood sample with the DNA whole blood kit (the QuickGene‐810 system, Fujifilm Europe GmbH, Düsseldorf, Germany) in accordance with the manufacturer's instructions. Variant screening of the RHD gene was performed as previously described 10 . Briefly, hemizygosity of the most common RHD deletion was first assessed by a long‐range polymerase chain reaction (PCR).…”

Weak D caused by a founder deletion in the RHD gene

“…Blood samples with a doubtful D phenotype (determined by routinely used serologic analyses) were obtained from several regional sites (i.e., Bretagne, Normandy, Pays‐de‐la‐Loire, Nord‐de‐France, Rhône‐Alpes, and Pyrénées‐Méditerranée) of the French Transfusion Organization (Etablissement Français du Sang) as previously described 2,3 …”

Applying molecular immunohematology discoveries to standards of practice in blood banks: now is the time

“…Approximately two‐thirds of these publications, however, would outright qualify as “molecular.” 29‐80 Many molecular immunohematology publications addressed routine clinical applications 29‐39 and clinical consequences 36‐43 . A large number of publications on basic transfusion medicine research topics 43‐76 document the need to explore genetic features and to collate the allelic variety present within and among the various populations worldwide 29,42,44,46‐54,71,73 . A Workshop on Molecular Methods in Immunohematology was sponsored in September 2006 by Food and Drug Administration (FDA)/Center for Biologics Evaluation and Research, Department of Health and Human Services Office of the Secretary/Office of Public Health and Science, National Institutes of Health/National Heart, Lung, and Blood Institute.…”