Common problems in routine pre-transfusion testing.
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Induced galactosuria is characterized by the excretion in urine of large amounts of new oligosaccharides, the structure of which are in connection with blood-group phenotypes ABH, Lewis and Secretor: O group : O-alpha-L fucopyranosyl-(1 leads to 2)-D galactopyranose et O-alpha-L fucopyranosyl-(1 leads to 2)-O-beta-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 4)]-O-beta-D 2-deoxy-2 acetamido-glucopyranosyl-(1 leads to 4)-[O-alpha-L fucopyranosyl-(1 leads to 6)]-D-galactopyranose. A group: O-alpha-D-2-deoxy-2 acetamido-galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 2)]-D galactopyranose et O-alpha-D-2-deoxy-2 acetamido-galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 2)]-O-beta-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 4)]-O-beta-D-2-deoxy-2 acetamido-glucopyranosyl-(1 leads to)-[O-alpha-L fucopyranosyl-(1 leads to 6)]-D galactopyranose. B group : O-alpha-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 2)]-D galactopyranose et O-alpha-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 2)]-O-beta-D galactopyranosyl-(1 leads to 3)-[O-alpha-L fucopyranosyl-(1 leads to 4)]-O-beta-D-2-deoxy-2 acetamido-glucopyranosyl-(1 leads to 4)-[O-alpha-L fucopyranosyl-(1 leads to 6)]-D-galactopyranose.
The application of adsorption chromatography on charcoal-Celite leads the authors to characterize in normal urines a class of fucose-rich oligosaccharides which possess blood group activities and are related to the phenotypes ABH, Le and secretor. Most of these oligosaccharides have a glucose residue in reducing terminal positions. Excretion of some oligosaccharides increases in the urine of diabetic and lactosuric subjects. In spontaneous or induced galactosurias, the elimination of oligosaccharides with a glucose residue in reducing terminal position decreases while appears a large amount of new oligosaccharides which all possess a galactose residue in reducing terminal position. These results lead to the conclusion that urinary oligosaccharides do not originate from glycosphingolipids, but from transglycosylation on carbohydrates which exist free in the organism: glucose for normal and diabetic subjects, lactose or galactose for lactosuric and galactosuric subjects, respectively.
The limited value of the antiglobulin phase of the cross match when a careful antibody screening is performed was demonstrated by analyzing 73,407 compatibility tests for 23,857 patients. By the blood grouping and screening of these patients, 178 cases were detected with unexpected blood group antibodies that had not been previously observed. Unexpected antibodies were detected in an additional 13 patients by the saline phase of the cross-match. In addition, the antiglobulin phase disclosed only one patient with a very weak anti-Lea and two patients whose sera gave doubtful reactions, possibly representing antibodies, but too weak to be identified.
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Statistical and serological evidence from a large kindred and two unrelated adults indicates that Targett (Tar) is an antigen in the Rh blood group system and that its presence is assocciated with a weak expression of the Rh antigen D. In the numerical notation the Tar antigen is designated Rh40.
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ABO and Rh (D--,dd) phenotype frequencies and gene frequencies are reported on 1547 pregnant women from different populations in the Outer Hebrides. There was significant heterogeneity of ABO gene frequencies in the Isle of Lewis, but not in or between other populations. More heterogeneity was apparent at the Rh locus, significant amounts being present between the populations of rural Lewis, between Lewis and Harris and between Lewis, Harris and the combined populations of North and South Uist, Benbecula and Barra. There was no evidence of heterogeneity due to religion in Benbecula or South Uist. Data on exogamy and endogamy suggest that migration between the various populations has been at a level sufficient to prevent or correct any tendency to genetic diversification. It is suggested tentatively that the heterogeneity observed may be the result of the massive emigration from the islands which has occurred over the last 150 years.
BACKGROUND: von Willebrand disease (VWD) is a common inherited bleeding disorder caused by low levels or activity of circulating von Willebrand factor (VWF). Genetic susceptibility to VWF antigen (VWF:Ag) below normal (≤ 50 IU/dL) in the general population is underexplored. OBJECTIVES: To identify genetic variants influencing VWF:Ag levels ≤ 50 IU/dL. METHODS: We performed a genome-wide association study in 926 cases with VWF:Ag levels ≤ 50 IU/dL and 12 846 controls from 7 studies from the Trans-Omics for Precision Medicine program. We then examined whether significant genome-wide findings were also associated with clinical diagnosis of VWD in 5 biobanks with 708 VWD cases and 1 286 069 controls, and with 6 bleeding and thrombotic disorders in FinnGen. RESULTS: Variants at 2 loci were associated (P < 5 × 10-9) with VWF:Ag levels ≤ 50 IU/dL: ABO and VWF. The VWF index variant, p.Tyr1584Cys, is a rare (0.22%) missense variant with odds ratio (OR) of 78.58, while the ABO index variant is a common intronic variant with a smaller effect (OR = 2.52). Notably, both VWF (OR = 7.16) and ABO (OR = 1.57) variants were also associated (P < .025) with diagnosed VWD. Among p.Tyr1584Cys heterozygotes, the penetrance of VWF:Ag levels ≤ 50 IU/dL was 24.2% and the penetrance of diagnosed VWD was 0.3%. p.Tyr1584Cys was associated (P < .0042) with increased odds of heavy menstrual bleeding (OR = 1.27), iron deficiency anemia (OR = 1.55), and intrapartum hemorrhage (OR = 2.20), but decreased odds of deep vein thrombosis (OR = 0.54). CONCLUSIONS: Although there are currently conflicting interpretations of pathogenicity p.Tyr1584Cys, our results suggest that it is a low penetrance pathogenic variant that contributes to VWF:Ag levels ≤ 50 IU/dL, bleeding, and VWD.
The distribution of ABO and RH blood groups was studied in 910 fertile women from the Isles of Lewis and Harris. The frequencies of group O mothers fell and of RH-mothers rose with increasing parity, but there were no significant changes in the ABO and RH blood group distributions among their offspring when they were subdivided according to their mothers' parity. When mother-offspring pairs classified according to their ABO and RH compatibility status it was found that RH incompatibility was associated with greater number of previous pregnancies and of abortions. Regression coefficients of birth weight on maternal stature and maternal age were significant only for doubly compatible female offspring and on number of previous pregnancies only for doubly compatible offspring of both sexes. When offspring were classified according to their own and their mothers' ABO blood groups, considerable variations in sex ratio were found. However, the only statistically significant finding was a deficit of A females among the offspring of O mothers. It is suggested that for the ABO blood groups system incompatibility selection, which favours homozygotes rather than heterozygotes, can be counterbalanced by selection for greater maternal tolerance of incompatible offspring with increasing parity. Hence the loss of heterozygotes in lower parity mothers may be compensated by an increase production in higher parity mothers. For the Rh system the same mechanism may occur, but there is evidence additionally of reproductive compensation.
These data comprise 1,231,024 routine tests carried out over a 5-year period on voluntary blood donors. The percentage of positive results on the machines varies from 1 to 3% of the total number of samples tested. Antibodies identified either by manual or automated techniques make up 15--20% of the positive screening reactions. Rhesus, Luewis and P systems prevail, whilst Duffy, Kidd and Ltheran systems are absent. This screening has three main advantages: the supply of plasma for our production of test sera, or therapeutic immunoglobulins; protection of the recipient; partial information on the donor's immunohaematological state, especially for the risk of giving him incompatible blood sometimes in the future.
Lods of +3.89 at a recombination fraction (theta) of 0.10 and recombinant:nonrecombinant counts of 2:16 indicate linkage between the Rd and Rh blood group loci. The possibility that Rd is the same as Sc is discussed.
Phenotype distributions of some genetic polymorphisms are reported in a sample of 721 diabetics and 515 non-diabetic, non-blood donor controls. Reference is also made, in the case of the ABO and Rhesus systems, to previously published results for blood donors resident in the Durham area. Non-insulin-taking diabetics show an increased frequency of blood group A1 (and A1 + A2) when compared with controls. This difference is particularly marked in male diabetics. When diabetics are compared with age matched controls, the difference is confined to the older cases. It is proposed that this effect is predominantly the result of a deficiency of group A1 in controls rather than the result of increased susceptibility to the disease among A1 people. No association with any of the Rhesus phenotypes is shown. In non-diabetics, the results suggest an enhanced survival value for the rr genotype. No significant associations are seen when the MNSs, Kell, Lewis, Duffy, haptoglobin, red cell acid phosphatase, phosphoglucomutase, adenylate kinase, and adenosine deaminase distributions in these groups of subjects are compared.-
Purified blood group-active substances derived from different pig, horse, baboon, Rhesus monkey and human tissues were quantitatively studied for their haemagglutination inhibiting potency with: (1) human IgM anti-A and anti-B; (2) human anti-Lea and anti-Leb; (3) Ulex europaeus extracts separated into lectin fractions with respective L-fucose-inhibitable ('anti-HF') and chitobiose-cellobiose-inhibitable ('anti-HC') combining sites. Irrespective of species origin, A and B blood group activity per milligram of purified material tended to be strikingly higher in substances low in, or devoid of, Lewis blood group activity. Most of the blood group substances displayed variable but about equally balanced amounts of Ulex anti-HF and anti-HC inhibiting activity. In contrast, pig submaxillary gland mucins displayed strikingly high levels of Ulex anti-HC inihibiting activity, even in the complete absence of Ulex anti-HF inhibiting activity. These serological findings are consistent with current biochemical concepts regarding the heterosaccharide microheterogeneity of blood group-active glycoproteins.
Of 3533 Rh-negative women who began a pregnancy without detectable Rh antibodies, 62 (1.8%) demonstrated evidence of Rh isoimmunization during pregnancy or within 3 days after delivery. All denied transfusions as well as abortions or previous pregnancies not followed by the administration of Rh immune globulin. Rh isoimmunization during pregnancy or within 3 days after delivery, which will not be prevented by the administration of Rh immune globulin after delivery, is the most important cause of residual Rh isoimmunization. A clinical trial of antenatal administration of Rh immune globulin, initially at 34 weeks's and subsequently at 28 and 34 weeks' gestation, in 1357 Rh-negative pregnant women who were delivered of Rh-positive babies, was effective in preventing the development of Rh isoimmunization during pregnancy or within 3 days after delivery. Antenatal prophylaxis with Rh immune globulin will be necessary if the incidence of Rh isoimmunization is to be reduced to its lowest possible level. Antenatal prophylaxis at 28 weeks' gestation is now an insured service in Manitoba.