Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accurate carrier detection in classic hemophilia has been difficult because of (1) technical problems related to the performance of both immunologic (VIII AGN) and procoagulant (VIII AHF) determinations, and (2) statistical problems related to the analysis of these data. VIII AHF was determined by a one-stage assay based on the partial thromboplastin time (PTT). VIII AGN was measured by the method of quantitative immunoelectrophoresis. The discriminant function U. = 0.67 1n (AHF) -- 3.17 AGN X 10(-3) was calculated for a validation group of 20 normal persons and for seven obligate carriers, and tested for accuracy of prediction on a cross-validation group of seven additional normal women and ten additional obligate carriers. A U. score of greater than or equal to 2.54 correctly identified 25 of 27 normal persons. Sixteen of 17 obligate carriers had U. scores below 2.54. In addition, of seven possilbe carriers, four were identified as normal and three as carriers. Five normal women taking oral contraceptives had disproportionately high U. scores. It is concluded that detection of carriers of classic hemophilia should be possible in the clinical laboratory by calculation of a discriminant function from combined measurements of VIII AGN and VIII AHF.
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PMID:Carrier detection in classic hemophilia by combined measurement of immunologic (VIII AGN) and procoagulant (VIII AHF) activities. 93 52

Intravenous adrenalin infusion (5 micrograms/kg, at most 160 micrograms in 10 min) normalized partial thromboplastin time (PTT) and ristocetin induced platelet aggregation (RIPA) in 4 of the 14 patients with von Willebrand's disease (VWD) in a short period of time. Although mean factor VIII (F-VIII) procoagulant activity was almost doubled 5 min following infusion, this was mainly observed in patients with relatively high baseline (> 2%) AHF activity. Mean F-VIII procoagulant activity rose by more than 100% following 10 days of corticosteroid treatment (deltacortil 2 mg/kg/day, at most 60 mg/day). PTT became normal in 6 of the 11 patients, but RIPA normalized only in 2. The improvement of RIPFA did not correspond to bleeding time in every patient. These results may suggest that if the baseline AHF activity is relatively high (greater than or equal to 9.5%), corticosteroid could be tried before schedule surgical intervention in patients with VWD.
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PMID:Effect of intravenous adrenalin infusion and corticosteroid treatment in patients with von Willebrand's disease. 677 88

The factor V (FV) B-domain is extremely important to the cofactor function of native FV for activated protein C (APC) in the inactivation of factor VIII (FVIII). In a previous study, we found that in the B-domain coding portion of DNA, the polymorphisms at nucleotide positions 2391, 2663, 2684, and 2863 were associated. In the major allele, all bases are A (A allele) and those in the minor allele are G (G allele). This study concerns itself with the question of whether or not there are differences in the APC response between the A allele and the G allele in plasma samples from persons without the FV Leiden. The APC ratios of homozygous carriers of the major A allele and the minor G allele do not differentiate themselves in classical activated partial thromboplastin time-based assays. In contrast, a test based on the deactivation of FVIII in the tenase complex in homozygous carriers of the minor G allele showed significantly lower APC ratios (P = 0.001) in comparison with the major A allele. The results of the investigation after modification of the test indicate that mutative changes in the B-domain apparently influence the interaction among phospholipids, APC, FV, and protein S. An increase in FVIII through the introduction of the FVIII concentrate Kogenate to the plasma samples was associated with a drop in the APC ratios of both genotypes. After defining 59 age- and sex-based matched pairs without the FV Leiden, the observed frequency of the minor G allele was higher in the non-thrombotic group (33.0%) than in the thrombotic group (22.8%). However, the difference did not reach the level of significance (odds ratio, 0.53; 95% confidence interval, 0.26-1.12). It does, nevertheless, appear possible that a homozygous condition for the minor allele in combination with a defect known to be associated with thrombophilia represents an additional thrombogenetic risk factor.
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PMID:Method-dependent influence of certain polymorphisms in the factor V B-domain on the response to activated protein C. 1099 91

A review of the literature suggests that assays accurate for the determination of factor VIII in plasma samples may not necessarily retain this accuracy when used for the determination of factor VIII in high-purity factor VII concentrates such as Hemofil M. Review of assay data suggests that it is imperative to obtain maximal activation of the factor VIII in the sample with thrombin when using an assay system of isolated coagulation factors such as the two-stage assay or the various chromogenic substrate assays. Based on a combination of ease and reproducibility of performance and correlation of in vivo and in vitro measurements. it is recommended that the one-stage activated partial thromboplastin time performed with plasma from an individual with severe hemophilia A be used for the measurement of factor VIII potency. Chromogenic substrate assays can be used if care is taken to assure optimal activation of factor VIII by thrombin in the assay and the presence of sufficient factor IXa, phospholipid and calcium ions to stabilize factor VIIIa during the assay process.
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PMID:Issues with the assay of factor VIII activity in plasma and factor VIII concentrates. 1168 46