1/5. Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family.The study of the molecular bases of thrombophilia in a large family with 4 symptomatic members is reported. Three thrombophilic genetic components (FV R506Q, FV H1299R, and PT 20210G/A), all affecting the activity of the prothrombinase complex, were detected alone and in combination in various family members. In addition, a newly identified missense mutation (factor V [FV] Y1702C), causing FV deficiency, was also present in the family and appeared to enhance activated protein C (APC) resistance in carriers of FV R506Q or FV H1299R by abolishing the expression of the counterpart FV allele. The relationships between complex genotypes, coagulation laboratory findings, and clinical phenotypes were analyzed in the family. All symptomatic family members were carriers of combined defects and showed APC resistance and elevated F1 2 values. Evidence for the causative role of the FV Y1702C mutation, which affects a residue absolutely conserved in all 3 A domains of FV, factor viii, and ceruloplasmin, relies on (1) the absolute cosegregation between the mutation and FV deficiency, both in the family and in the general population; (2) FV antigen and immunoblot studies indicating the absence of Y1702C FV molecules in plasma of carriers of the mutation, despite normal levels of the FV Y1702C messenger rna; and (3) molecular modeling data that support a crucial role of the mutated residue in the A domain structure. These findings help to interpret the variable penetrance of thrombosis in thrombophilic families and to define the molecular bases of FV deficiency. (blood. 2000;96:1443-1448)- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/5. Acquired and transient RBC CD55 deficiency (Inab phenotype) and anti-IFC.BACKGROUND: antigens of the Cromer blood group system reside on the glycoprotein CD55 (decay-accelerating factor). The Inab phenotype is the null phenotype of this system. So far, only five propositi have been described who exhibit this phenotype, and single-nucleotide substitutions in the CD55 gene have been found in three of them. This report describes the first example of a patient with an acquired and transient form of the Inab phenotype. CASE REPORT: A 54-year-old black patient was admitted to the hospital because of abdominal pain. Multiple splenic infarctions were visualized in the abdominal computerized tomography scan, and a prophylactic splenectomy was performed. The patient's serum reacted by an IAT with all donor RBCs tested. RESULTS: Serologic analysis showed that the patient had the rare Inab phenotype and that his serum contained anti-IFC. flow cytometry demonstrated the absence of CD55 on his RBCs, whereas lymphocytes, monocytes, granulocytes, and platelets expressed CD55, albeit at a weaker level than cells of common phenotypes. cDNA revealed no differences from the published sequences. flow cytometry performed 12 months after splenectomy showed reappearance of the CD55 antigen; serologic tests performed after 17 months revealed that the anti-IFC had almost disappeared and that the RBCs were again agglutinated by various Cromer antibodies. CONCLUSION: A patient with an acquired and transient form of the Inab phenotype is described, in whom the CD55 deficiency is limited to the RBCs and is associated with splenic infarctions.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/5. Anti-Vel reactivity diminished by adsorption with rabbit RBC stroma.BACKGROUND: An anti-Vel, nearly missed in antibody identification studies, and the effect of a commercially available rabbit RBC stroma (rest, Immucor) adsorptions on eight anti-Vel sera are reported. Anti-Vel is an antibody to an antigen of high prevalence. CASE REPORT: A 48-year-old woman with chronic vaginal bleeding presented with a Hct of 14.7 percent. The transfusion service was not informed of her history of anti-Vel when she was transferred from another institution. Studies performed on an emergency request for transfusion were interpreted as a cold autoantibody as adsorption with a commercial source of rest eliminated the reactivity. Stored anti-Vel sera were tested by titration studies before and after adsorption with commercial rest. RESULTS: serum from the index case did not react after adsorption with rest at the transfusion service. Studies with the stored anti-Vel indicated antibody adsorption with four of four samples at immediate spin (IS) and room temperature (RT) phases, four of eight samples at 37 degrees C in albumin (ALB) phase, and four of eight samples at ALB-IgG-AGT phase. Variations in antibody reactivity were observed in the samples tested, but rest adsorption diminished antibody reactivity in most samples. All eight stored sera demonstrated some reactivity in at least one phase after adsorption with rest. CONCLUSION: Anti-Vel was completely or partially adsorbed by rest. Caution should be used when interpreting cold agglutinins with this method. The manufacturer warns that uncommon alloantibodies may be adsorbed.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/5. thrombophilia found in patients with moyamoya disease.Sixteen patients with moyamoya disease and four with quasi-moyamoya disease were investigated in order to elucidate the presence of thrombophilia. The assay system for diagnosing thrombophilia consisted of assessing both the activity and antigen levels of antithrombin iii, protein C, protein S, fibrinogen and plasminogen as well as detecting lupus anticoagulants. The analysis revealed that one third (four definite cases and three quasi-cases) of the examined patients demonstrated either congenital or acquired thrombotic tendency. protein c deficiency was found in two definite cases and in two quasi-cases among whom one quasi-case was identified to have a hereditary type I protein c deficiency. protein s deficiency was found in one definite case and in one quasi-case. Type II plasminogen deficiency was found in one quasi-case, and lupus anticoagulant was present in one quasi-case. Based on these findings, an evaluation of thrombophilia should thus be performed when both diagnosing and treating suspected cases of moyamoya disease.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/5. A novel and de novo spontaneous point mutation (Glu271STOP) of the antithrombin gene results in a type I deficiency and thrombophilia.We describe a novel, de novo point mutation in one antithrombin (AT) allele resulting in type I AT deficiency and thrombophilia. Low plasma AT activity as well as low plasma AT antigen were documented in the propositus, but not in the parents, or in a male sibling. AT gene analysis by sequencing polymerase chain reaction-amplified genomic dna from exon 5 of the propositus revealed a novel point mutation, GAG-->TAG at codon 271, resulting in a stop codon (Glu271STOP). This mutation was not demonstrable in the other members of his immediate family. dna marker polymorphism analysis indicated the expected parentage. Based on allele frequency data for Caucasians in the united states the cumulative paternity index, or CPI, for the propositus and his father is 219,077. This corresponds to a probability of paternity of 99.9995% based on a prior probability of 50%. Included in this analysis is a linkage analysis of a trinucleotide repeat in intron 5 of the AT gene of the various family members, which also confirmed maternity and paternity. These studies provide documentation of the first spontaneous mutation of an AT gene in a thrombophilic individual, resulting in a type I AT deficiency.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |