Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhesus D (RhD) typing is performed by agglutination methods; however, in clinical situations where these techniques cannot be performed, RhD DNA typing is an alternative approach. The Rh antigens are encoded by the RHD and RHCE genes. In RhD-negative individuals the RHD gene is absent or grossly deleted, but variations in the arrangement of the RH locus in different populations are emerging. The aim of this study was to analyse the gross organization of the RH genes in our population using a previously described multiplex polymerase chain reaction (PCR) method with some modifications. We studied 253 DNA samples from Argentinian blood donors, 15 samples with a reduced expression of the D antigen and 1 Dc- phenotype. We evaluated the clinical utility of this method to ascertain the RhD antigen in 10 patients with warm-type autoimmune haemolytic anaemia (AIHA) and 14 samples of amniotic fluids. All Rh phenotypes were properly characterized and no discrepancies with serological typing were found. Analyses performed in the Dc- phenotype suggest the presence of a hybrid RHCE-RHD gene. DNA typing confirmed the RhD-negative type of one AIHA sample in which serological tests were inconclusive. Foetal DNA typing correctly indicated the RhD in every foetus. VNTR (variable number of tandem repeats) and STR (short tandem repeats) analysis detected maternal contamination in two amniocentesis samples and confirmed the foetal origin of 12. This multiplex PCR strategy is suitable for RhD determination in clinical situations in which serological typing cannot be accomplished with its usual ease.
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PMID:Molecular determination of RhD phenotype by DNA typing: clinical applications. 1108 23

We have determined whether derivated fetal haemoglobin (dHbF, consisting of glycated and acetylated HbF) can be used as a cell age marker for fetal red blood cells (RBCs). Cord blood was obtained between 19 and 39 weeks of gestation from 28 alloimmunised anaemic fetuses (23 RhD+ and 5 Kell) and from 20 non-anaemic fetuses and newborns (controls). Density gradient centrifugation was applied to 36 samples (20 RhD+, 15 controls and 1 Kell) to obtain fractions of increasing cell age. Blood samples were used for measurements of mean cellular volume (MCV), mean cell haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), pyruvate kinase activity (PK) and derivated fetal haemoglobin (dHbF) by cation-exchange HPLC. Reticulocytes were counted only in the whole blood samples. In all density gradient separated RBC fractions, the values for MCV, MCH and PK activity decreased and those of MCHC and dHbF increased with increasing density (equivalent to increasing cell age). The mean density was lower for RBCs of the anaemic RHD group (1.072+/-0.007 g/ml) than for the non-anaemic controls (1.077+/-0.005 g/ml) (p<0.05) The RBC density of the Kell sensitised fetus did not differ from those of the controls. In the control group, the values of the cell age markers in whole blood changed significantly with the gestational age, showing an increase of mean age of the erythrocyte population. The best linear relationship was found for dHbF (y=6.28+0.17*weeks; r=0.84; p<0.001). In the anaemic RhD+ fetuses, the RBC age markers did not change with gestational age; the dHbF percentages were lower, and the MCV, MCH, PK values and the reticulocyte counts were higher than in the controls (0.05<p<0.001). The dHbF values of the Kell sensitised fetuses were above (p<0.01) and the reticulocyte counts were below normal (p<0.05) for gestational age. For the anaemic fetuses, a significant number of the dHbF values (86%) and of the reticulocyte counts (78%) differed from the values of the controls (p<0.01). The dHbF percentages in RhD+ fetuses showed the best correlation with the Hb deficit, which is a measure for anaemia (r=-0.81, p<0.0001). We conclude that the percentage derivated HbF may indicate whether the RBC production is normal for gestational age. It may in that sense reflect stimulated or impaired erythropoiesis in alloimmunised haemolytic anaemia.
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PMID:Derivated fetal haemoglobin as a marker for red cell age in the human fetus reflecting stimulated or impaired red blood cell production. 1149 84

The Rh antigens are encoded by the RHD and RHCE genes. In RhD negative individuals the RHD gene is absent or grossly deleted. Routinely, Rh typing is performed by haemagglutination. However, there are some clinical situations in which serological techniques are not suitable for determining the red blood cell phenotype accurately. Most anti-D sera may not agglutinate erythrocytes possessing a reduced expression of the D antigen. In these cases, DNA-based analyses may be better than serological typing to infer the appropriate phenotype. Agglutination methods are also of limited use for determining the red blood cell phenotype of a foetus at risk of haemolytic disease of the newborn. Molecular RHD typing using amniocytes or DNA obtained from maternal plasma may obviate the need of amniocenteses during pregnancy when the foetus is RhD negative, thus providing an important tool in managing possible sensitization by foetal erythrocytes. Classical haemagglutination has limitation in patients with autoimmune haemolytic anaemia. Erythrocytes coated with IgG cannot be accurately typed for red blood cell antigens, particularly when directly agglutinating antibodies are not available or IgG removal by chemical treatment is insufficient. Molecular genotyping is very important for determination of the true blood group antigens of these patients. RHD genotyping with a specificity and sensitivity comparable to serologic methods is of practical importance to overcome the limitations of serology and, in addition, to improve the currently possible resolution.
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PMID:Clinical aspects of Rh genotyping. 1207 77

Antenatal determination of fetal blood group is important in pregnancies with a significant risk of hemolytic anemia due to maternal alloimmunization. The International Blood Group Reference Laboratory (part of the National Blood Service) in Bristol, UK, provides a fetal blood group genotyping service to obstetricians caring for immunized pregnant women with heterozygous partners. Since 2001, fetal D typing has been offered using free fetal DNA in maternal plasma. Real-time polymerase chain reaction (PCR) assays are performed to detect the RHD gene. To confirm the presence of fetal DNA when RHD is not detected, Y-chromosome sequences are targeted. When a D-negative female fetus is predicted, maternal buffy coat DNA is tested for eight insertion/deletion polymorphisms. Sequences that are absent from the maternal genome are then targeted in maternal plasma and are used to confirm the presence of free fetal DNA in the blood sample. Currently, 283 pregnancies have been tested, of which 50 are awaiting confirmatory results. Fetal D status was correctly predicted in 223 cases, and no result was obtainable in 7 cases. In three cases, serology on cord blood was discrepant with reported results, but all fetuses had received multiple intrauterine transfusions. The new test has significantly reduced the number of invasive procedures carried out in the UK for fetal D grouping. Antenatal anti-D prophylaxis is currently being introduced in the UK to all D-negative women; in the future, detection of fetal RHD sequences in maternal plasma may allow anti-D to be restricted to pregnancies involving a D-positive fetus.
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PMID:A clinical service in the UK to predict fetal Rh (Rhesus) D blood group using free fetal DNA in maternal plasma. 1525 49

Initial Rh phenotyping of a man with hemolytic anemia, his wife, and son appeared to exclude paternity. No exclusion was found in other blood groups or in the human leukocyte antigen (HLA) system; excluding Rh, the paternity index was 98.58 percent. Samples from these three family members, and two other family members, were tested with additional Rh antisera. The results indicated that the propositus has an Rhmod phenotype with expression of c, weak e, and very weak D, E, and G antigens. To support this hypothesis, DNA analysis of the RHD and RHCE genes was performed on the five family members. Polymerase chain reaction (PCR) products from exons 2 and 5 were analyzed by denaturing gradient gel electrophoresis (DGGE). The DNA results corroborated the serologic findings and refuted the exclusion of paternity.
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PMID:Rhmod phenotype: a parentage problem solved by denaturing gradient gel electorphoresis of genomic DNA. 1538 27

Rh (Rhesus) proteins (D, CcEe) are expressed in red cells (RBC) in association with other membrane proteins (RhAG, LW, CD47 and GPB). By interacting with the spectrin-based skeleton through protein 4.2 and ankyrin, the Rh complex contributes to the maintenance of the mechanical properties of the erythrocyte membrane. The RH system is one of the most immunogenic and polymorphic human blood group system. Molecular basis of most Rh phenotypes, including the Rh(null) phenotype associated with hemolytic anemia, have been determined. The demonstration that the RHD-positive locus is composed of the RHD and RHCE genes, whereas the RHD gene is deleted in most RhD-negative individuals, allowed fetal RhD genotyping by non-invasive PCR assays for antenatal diagnosis of pregnancy at risk for Rh hemolytic disease of the newborn. In mammals, the Rh protein family includes two non-erythroid members, RhBG and RhCG, mainly expressed in liver and kidney, two organs specialized in ammonia genesis and excretion. Functional analyses in heterologous systems revealed that RhAG, RhBG and RhCG can mediate ammonium (NH(3) and/or NH(4)(+)) transport across the cell membrane and might represent mammalian specific ammonium transporters. Furthermore, recent studies performed in human and murine red blood cells (RBC) indicate that RhAG facilitates CH(3)NH(2)/NH(3) movement across the membrane and represents a potential example of gas channel. The crystallographic structure of the bacterial ammonia channel AmtB and functional studies showing that AmtB conducts NH(3) into reconstituted vesicles is fully consistent with these latter studies. In RBCs, RhAG may transport NH(3) to detoxifying organs like kidney and liver and with non-erythroid tissues orthologs may contribute to regulation of the acid-base balance.
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PMID:Rh proteins: key structural and functional components of the red cell membrane. 1596 Dec 4

The Rh system clinically is one of the important blood groups. The major Rh antigens are RhD, RhC/c, and RhE/e, which are carried by two integral membrane polypeptides consisted of 416 amino acids. These polypeptides are encoded by two closely related genes, RHD and RHCE. Both RH genes are composed of ten exons. It is thought that multiple recombinations, nucleotide substitutions, large nucleotide gaps (due to Alu sequence), and high level of the homology between the RHD and RHCE genes are the important factors in the formation and evolution of these genes. The RHD gene is deleted in most white individuals who lack the RhD antigen, while 12% of Japanese individuals have an RHD gene. Molecular analyses have elucidated the background of various Rh-related variants; D--, partial D, weak D, and Rhnull. The Rhnull phenotype is divided into the most common type by the Rhnull regulator gene and second type by the amorph gene that arose by homozygosity of a silent allele at the RH locus. The RhAG glycoprotein has been regarded as a most critical Rhnull gene of the reglurator type and a critical co-expressing factor of the Rh polypetides on red blood cells. Studies on the autoantibodies against red blood cells in aoutoimmune hemolytic anemia have suggested that the public epitopes of autoantigens exist on the Rh polypeptides.
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PMID:[Molecular approaches to the Rh blood group system]. 1713 12