Fatal hemolytic disease of a newborn due to anti‐D in an Rh‐positive D<sup>u</sup> variant mother*

Lacey, P A; Caskey, C R; Werner, Dudley; Moulds, John J.

doi:10.1046/j.1537-2995.1983.23283172867.x

Cited by 88 publications

(37 citation statements)

References 15 publications

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“…Although D variants are rare and their relative immunogenicity poorly documented, RhD immunization of a Dnegative mother by D Va fetal red cells has been described (Mayne et al, 1990), as well as of a D VI mother with Dpositive fetal red cells (Lacey et al, 1983). The frequency of false-negative (and false-positive, see above) events should be considerably reduced (or avoided) if at least two pairs of primers probing different regions of the RHD gene are used in routine analysis.…”

Section: Discussionmentioning

confidence: 99%

Specificity and sensitivity of RHD genotyping methods by PCR‐based DNA amplification

Jt¹,

Kim

Mouro

et al. 1997

Br J Haematol

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Summary.We have compared the sensitivity and specificity of four PCR methods of RHD gene detection using different sets of primers located in the regions of highest divergence between the RHD and RHCE genes, notably exon 10 (method I), exon 7 (method II), exon 4 (method III) and intron 4 (method IV). Methods I-III were the most sensitive and gave a detectable signal with D-pos/D-neg mixtures containing only 0 . 001% D-positive cells. Moreover, method II could detect the equivalent DNA amount present in only three nucleated cells in the assay without hybridization of PCR products, whereas the sensitivity of the other methods was 10-50 times less. Investigation of D variants indicated that false-negative results were obtained with method II (D IVb variant), method III (D VI and DFR variants) and method IV (D VI variants), but not method I. Weak D (D u ) was correctly detected as D-positive by all methods, but most cases of Rh null appeared as false-positives, as they carry normal RH genes that are not phenotypically expressed. Some false-positive results were obtained with method I in a few Caucasian DNA samples serotyped as RhD-neg but carrying a C-or E-allele, whereas a high incidence of false-positives was found among non-Caucasian Rh-negative samples by all methods. In the Caucasian population, however, we found a full correlation between the predicted genotype and observed phenotype at birth of 92 infants. Although we routinely use the four methods for RHD genotyping, a PCR strategy based on at least two methods is recommended.

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Section: Discussionmentioning

confidence: 99%

Specificity and sensitivity of RHD genotyping methods by PCR‐based DNA amplification

Jt¹,

Kim

Mouro

et al. 1997

Br J Haematol

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“…Subsequently, case reports revealed that some women with a D U phenotype who had been exposed to D+ RBCs by transfusion or pregnancy formed anti-D (Argall et al , 1953; Simmons &Krieger, 1960; Ostgard et al , 1986; Mayne et al , 1991; Domen & Hoetge, 1997). Additional pregnancies were reported that were complicated by RhD haemolytic disease of the fetus and newborn (Hill et al, 1974; White et al , 1983; Lacey et al , 1983; Cannon et al , 2003). To protect RhD-negative women from exposure to the D antigen and forming anti-D (RhD alloimmunization) by transfusion of RBCs from a donor with a D U variant antigen, policies were developed in the United States requiring RBCs from blood donors who tested initially negative by anti-D to be retested with anti-human globulin (a “weak D test”) (Scientific Committee of the Joint Blood Council & Standards Committee of the American Association of Blood Banks, 1958).…”

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confidence: 99%

Serological weak D phenotypes: a review and guidance for interpreting the RhD blood type using the RHD genotype

2017

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Summary Approximately 0.2% to 1% of routine RhD blood typings result in a “serological weak D phenotype.” For more than 50 years, serological weak D phenotypes have been managed by policies to protect RhD-negative women of child-bearing potential from exposure to weak D antigens. Typically, blood donors with a serological weak D phenotype have been managed as RhD-positive, in contrast to transfusion recipients and pregnant women, who have been managed as RhD-negative. Most serological weak D phenotypes in Caucasians express molecularly defined weak D types 1, 2 or 3 and can be managed safely as RhD-positive, eliminating unnecessary injections of Rh immune globulin and conserving limited supplies of RhD-negative RBCs. If laboratories in the UK, Ireland and other European countries validated the use of potent anti-D reagents to result in weak D types 1, 2 and 3 typing initially as RhD-positive, such laboratory results would not require further testing. When serological weak D phenotypes are detected, laboratories should complete RhD testing by determining RHD genotypes (internally or by referral). Individuals with a serological weak D phenotype should be managed as RhD-positive or RhD-negative, according to their RHD genotype.

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“…[2][3][4][5][6][7][8][9][10][11][12] In at least 3 cases, a subsequent pregnancy was complicated by fatal Rh hemolytic disease of the fetus or newborn. [13][14][15] In an effort to decrease this risk of pregnancy, the editors of Standards for Blood Banks and Transfusion Services (hereafter Standards) of the American Association of Blood Banks (now AABB) advised that a test for weak D was ''unnecessary when testing recipient red cells.'' 16(58) The intent of this guidance was to encourage transfusion services to use Rh typing methods that would categorize women of childbearing potential (and other patients) who had a weak D phenotype as Rh negative.…”

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confidence: 99%

Policies and Procedures Related to Testing for Weak D Phenotypes and Administration of Rh Immune Globulin: Results and Recommendations Related to Supplemental Questions in the Comprehensive Transfusion Medicine Survey of the College of American Pathologists

Sandler

Roseff

Domen

et al. 2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.—Advances in RHD genotyping offer an opportunity to update policies and practices for testing weak D phenotypes and administration of Rh immune globulin to postpartum women. Objectives.—To repeat questions from a 1999 College of American Pathologists proficiency test survey, to evaluate current practices for testing for weak D and administration of Rh immune globulin, and to determine whether there is an opportunity to begin integrating RHD genotyping in laboratory practice. Design.—The College of American Pathologists Transfusion Medicine Resource Committee sent questions from the 1999 survey to laboratories that participated in the 2012 proficiency test survey. The results of the 2012 survey were compared with those from 1999. Results from published RHD genotyping studies were analyzed to determine if RHD genotyping could improve current policies and practices for serological Rh typing. Results.—More than 3100 survey participants responded to the 2012 questions. The most significant finding was a decrease in the number of transfusion services performing a serological weak D test on patients as a strategy to manage those with a weak D as Rh negative (from 58.2% to 19.8%, P < .001). Data from RHD genotyping studies indicate that approximately 95% of women with a serological weak D could be managed safely and more logically as Rh positive. Conclusions.—Selective integration of RHD genotyping policies and practices could improve the accuracy of Rh typing results, reduce unnecessary administration of Rh immune globulin in women with a weak D, and decrease transfusion of Rh-negative red blood cells in most recipients with a serological weak D phenotype.

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Fatal hemolytic disease of a newborn due to anti‐D in an Rh‐positive D^u variant mother*

Cited by 88 publications

References 15 publications

Specificity and sensitivity of RHD genotyping methods by PCR‐based DNA amplification

Specificity and sensitivity of RHD genotyping methods by PCR‐based DNA amplification

Serological weak D phenotypes: a review and guidance for interpreting the RhD blood type using the RHD genotype

Policies and Procedures Related to Testing for Weak D Phenotypes and Administration of Rh Immune Globulin: Results and Recommendations Related to Supplemental Questions in the Comprehensive Transfusion Medicine Survey of the College of American Pathologists

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Fatal hemolytic disease of a newborn due to anti‐D in an Rh‐positive Du variant mother*

Cited by 88 publications

References 15 publications

Specificity and sensitivity of RHD genotyping methods by PCR‐based DNA amplification

Specificity and sensitivity of RHD genotyping methods by PCR‐based DNA amplification

Serological weak D phenotypes: a review and guidance for interpreting the RhD blood type using the RHD genotype

Policies and Procedures Related to Testing for Weak D Phenotypes and Administration of Rh Immune Globulin: Results and Recommendations Related to Supplemental Questions in the Comprehensive Transfusion Medicine Survey of the College of American Pathologists

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Fatal hemolytic disease of a newborn due to anti‐D in an Rh‐positive D^u variant mother*