Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative sensitivities of the prothrombin time, Russell's viper venom time and activated partial thromboplastin time were determined in one-stage quantitative assays for factor V and factor X. Sensitivity was defined as the slope of the reference curve. The prothrombin time was the most sensitive test for factor X and the least sensitive for factor V. The Russell's viper venom time was the most sensitive test for factor V and least sensitive for factor X. The activated partial thromboplastin time approximated the sensitivity of Russell's viper venom for factor V and had intermediate sensitivity for factor X. The data indicate that factor V is best quantitated by the Russell's viper venom time and factor X by the prothrombin time, exactly the opposite of what is customarily done.
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PMID:Quantitative one-stage assays for factors V and X. 120 39

Previous studies showed that factor V consists of multiple oligomeric forms including a minor component (form L) which contained lipid and was eluted in the excluded volume of a Sepharose 4B column. In the present and following study the hypothesis that factor V is a lipid requiring protein rather than a lipoprotein has been tested. Modification of a previous purification procedure resulted in the separation of factor V from lipoprotein. The lipid extracted from this lipoprotein was qualitatively similar to that previously isolated from form L. Removal of this lipoprotein by sucrose density gradient ultracentrifugation resulted in the isolation of factor V of high specific activity which contained no detectable phospholipid and less than 0.2% cholesterol. No component was excluded from Sepharose 4B after gel filtration of this purified preparation. It is concluded that factor V is not a lipoprotein, but rather a protein which requires lipid for its coagulant properties. To define this requirement further the ability of factor V-phospholipid complexes to accelerate the conversion of prothrombin to thrombin by factor Xa in the presence of calcium was tested. The rate of thrombin formation was highly dependent on the phospholipid employed with each active phospholipid exhibiting a characteristic optimal concentration. At 250 muM, the order of activity was phosphatidyl ethanolamine greater than phosphatidyl inositol greater than cardiolipin greater than phosphatidyl choline. Phosphatidyl serine was inert at all concentrations employed. No single fatty acid was consistently present in active lipid preparations, nor was a specific fatty acid absent from those which had no clotting activity. In comparing different lipid classes, a direct relationship between the overall degree of unsaturation and activity was not observed. However, bovine phosphatidyl inositol, which is highly unsaturated, is active, while plant phosphatidyl inositol, which contains only trace amounts of unsaturated fatty acids, were inert. At lipid concentrations below 300 muM, saturated phosphatidyl ethanolamine produced by hydrogenation of bovine phosphatidyl ethanolamine was less active than an equal concentration of the native lipid. In mixtures containing both lipids, artificially saturated phosphatidyl ethanolamine potentiated the activity of the native compound.
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PMID:Determinants of the formation and activity of factor V-phospholipid complexes. I. Influence of phospholipid structure. 123 44

In order to investigate the safety of prolonged heparinless venoarterial bypass (HL-VAB), we subjected 18 sheep to prolonged HL-VAB for up to 6 days. Three animals died of granulomatous lung abscess and one died from intra-abdominal abscess. One animal died of generalized thromboembolism secondary to mechanical damage of the nonthrombogenic coating occurring at the time of cannulation. HL-VAB was successfully carried out in 13 sheep. Although clots were found at all tubing connections where blood turbulence occurred, only the previously mentioned animal showed evidence of thromboembolism. Damage to the nonthrombogenic tubing exposed to the roller pump head was seen in all animals, and its severity appeared to be related to the duration of bypass. Scanning electron microscopic examination revealed scattered platelet aggregates on the nonthrombogenic coated surfaces without clinical evidence of embolization. Hematocrit values, leukocyte counts, platelet counts, prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT), plasma fibrinogen levels, and factor V and VIII levels remained unchanged, whereas free plasma hemoglobin levels rose slightly during 6 days of HL-VAB. HL-VAB for up to 6 days appears to have little adverse effect on blood cells and blood coagulation factors. For current clinical use, the nonthrombogenic coated tubing circuit should be changed every 48 hours because of time-related trauma to the coated tubing from the roller pump.
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PMID:Successful prolonged heparinless venoarterial bypass in sheep. 126 48

Bovine plasma factor V has been isolated by a preparative procedure involving barium sulfate adsorption, QAEC extraction, poly(ethylene glycol) precipitation, and finally chromatography on a desulfated Sepharose 6B column. Factor V was recovered as a single peak in yields of 35-40% with a specific activity of 50-70 representing a purification of 1000-2000-fold relative to the starting plasma. The apparent molecular weight of the purified factor V was 439,000 +/- 5000. On sodium dodecyl sulfate gel and analytical gel electrophoresis, this factor V preparation showed multiple bands, but results are inconclusive with regard to a possible subunit structure for this factor. The purified factor V was stable for at least 1-2 weeks when stored at 4 degrees C in 0.2 M Tris-acetate, 50 mM CaCl2, 10% glycerol, pH 7.5. When stored at -20 degrees C in 50% glycerol, this preparation was stable for several months. Treatment of the purified factor V with bovine factor Xa, RVV-V, thrombin, or chymotrypsin (but not trypsin) led to a seven- to ten-fold increase in clotting activity and a concomitant decrease in apparent molecular weight. The latter was comparable for each activation system yielding the following average molecular weight values: factor VaSa, 246,000-, factor Va RVV-V, 251,500; Factor Vathr, 239,000; alpha-chymotrypsin, but not trypsin, can activate plasma factor V yielding a product similar to that observed with the above activators. The molar quantities of each of the activators required varied considerably with thrombin having the highest specific activity and factor Xa the lowest. Activation by factor Xa was greatly facilitated by the addition of phospholipid. In the presence of a mixture of phosphatidylcholine/phosphatidylserine (1:1, w/w), the activation of factor V by factor Xa plus Ca2+ required one-third the amount of factor Xa protein as that required in the absence of phospholipid. Even though each of these activators appears to act in an enzymatic manner, the chemical nature of the conversion is unknown at this time.
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PMID:The activation of factor V by factor Xa or alpha-chymotrypsin and comparison with thrombin and RVV-V action. An improved factor V isolation procedure. 126 97

A patient with combined factor V and factor VIII deficiency is presented. The bleeding manifestations were: easy bruising, post-traumatic bleeding, bleeding after tooth extractions. The main laboratory feature was a prolonged partial thromboplastin time which was corrected by the addition of adsorbed normal plasma but not by the addition of normal serum, hemophilia A plasma of another patient with combined factor V and factor VIII deficiency. The thromboplastin generation test was clearly abnormal and was corrected by the addition of adsorbed normal plasma but not by addition of normal serum. Prothrombin consumption was also defective. Prothrombin time was slightly prolonged too, Thrombin time, platelet and vascular tests were within normal limits and there was no hyperfibrinolysis. Factor VIII was 8% of normal, whereas factor V was 14% of normal. Factor VIII associated antigen was normal. All other clotting factors were within normal limits. The parents of the propositus were consanguineous (first cousins) but had normal factor V and factor VIII activity and normal factor VIII antigen. The same was true for other family members. The hereditary transmission of the condition appears autosomal recessive.
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PMID:Combined deficiency of factor V and factor VIII. A report of another case. 127 81

The extent and time course of changes in selected procoagulant and anticoagulant factors were investigated in 19 patients undergoing elective abdominal aortic surgery. The coagulation factors were measured preoperatively, and on days two, four, and six postoperatively. It was found that there were no significant changes outside the normal range in prothrombin time, partial thromboplastin time, or thrombin clotting time. However, there were large increases in the procoagulants, fibrinogen, factor VIII coagulant, factor VIIIRag/von Willebrand factor, and in alpha 1-antitrypsin. Over the same time there were marked decreases in the naturally occurring anticoagulants, protein C and antithrombin III, and in alpha 2-macroglobulin. These changes implied that the patients were "hypercoagulable" in the postoperative period. The maximum changes in the procoagulants occurred on either postoperative day two or day four. The maximum changes in the natural anticoagulants occurred on postoperative day two. There were no significant changes in factor V, factor X, alpha 2-antiplasmin, or platelet aggregability. The timing of the changes coincided with a period of high risk of perioperative myocardial infarction in this group of patients. Thus, it is possible that postoperative hypercoagulability contributes to the development of coronary artery thrombosis and myocardial infarction following abdominal aortic surgery.
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PMID:Postoperative changes in coagulant and anticoagulant factors following abdominal aortic surgery. 128 42

The crude venom of many elapid snakes appeared to contain proteins that activated blood coagulation factor V. The factor V activator present in the venom of Naja naja oxiana was purified to homogeneity by chromatography on a mono-S column. The activator was a single chain protein with an apparent mol. wt of 48,000, as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and by gel permeation chromatography on Sephacryl S200. Activation of bovine factor V by the purified venom activator was accompanied by proteolytic cleavage of factor V and resulted in the formation of two major polypeptide chains with mol. wts of about 90,000 and 77,000. The final product obtained was compared with thrombin-activated factor V for its ability to function as cofactor in factor Xa-catalysed prothrombin activation in the presence of negatively charged phospholipid vesicles (5 mole% phosphatidylserine/95 mole% phosphatidylcholine). The Km for prothrombin obtained at a saturating amount of venom-activated factor Va was nine-fold higher than with thrombin-activated factor V (0.83 microM vs 0.09 microM, respectively) whereas both factor Va molecules stimulated the Vmax of thrombin formation some 6000-fold. Both forms of factor Va promoted the binding factor Xa to negatively charged phospholipid vesicles. However, the apparent Kd for factor Xa was less favorable in the presence of venom-activated factor V (0.67 x 10(-9) M) than in the presence of thrombin-activated factor V (0.043 x 10(-9) M). Thrombin cleaved a peptide bond in the 77,000 mol. wt polypeptide chain of venom-activated factor V, which resulted in the formation of a normal factor Va light chain. This peptide bond cleavage was, however, not associated with a change of cofactor activity. Venom treatment of thrombin-activated factor V, on the other hand, did remove a small fragment (mol. wt approximately 4000) from the heavy chain of factor Va (94,000), yielding a molecule with reduced cofactor activity. The diminished cofactor activity of venom-activated factor V is, therefore, likely due to the fact that a small peptide fragment, involved in the interaction with prothrombin and factor Xa, is missing from the heavy chain of venom-activated factor V.
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PMID:Activation of bovine factor V by an activator purified from the venom of Naja naja oxiana. 144 Jun 44

Dynamics of protein C concentration was studied in rat blood after administration of thrombin and thromboplastin. Administration of 0.5 ml 1% thromboplastin caused fast decrease of protein C concentration, down to 60% of the initial level, within 3 min, while activity of factor V reached the minimal rate (30%) within 5 min. Content of protein C returned to the initial level in blood within 2-2.5 hrs and of factor V--within 6 hrs. After administration of thrombin 3 NIH in content of protein C was decreased to 91.3% whereas heparin was released only after injection of 6 NIH. The data obtained suggest that the protein C system responded earlier to occurrence of thrombin in circulation as compared with the neurohumoral regulators of the anticoagulation system; the protein C system is one of primary mechanisms of the antithrombosis defence.
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PMID:[Participation of protein C in reaction of the anti-coagulant system to intravenous administration of thrombin and thromboplastin to rats]. 144 Dec 96

This study examines the assumption that both the anticoagulant and fibrinolytic activity that follow the generation of thrombin induced by infusion of factor Xa/PCPS are due to generation of activated protein C. Untreated controls or animals given unrelated antibody were compared with animals pretreated with a specific monoclonal antibody to protein C (HPC4). Compared with untreated controls excess HPC4 substantially reduced the level of protein C activation as observed by protein C immunoblotting and enzyme-linked immunosorbent assay for antitrypsin/activated protein C complexes. Despite this, the anticoagulant activity as reflected by the decline of factors Va and VIIIa levels (as observed by coagulation assays and by factor V immunoblotting) was significantly greater than controls. The fibrinolytic activity (as observed by assays of tissue plasminogen activator, D-Dimer, alpha 2-antiplasmin) also was significantly greater than controls. We conclude that neutralization of the protein C anticoagulant system while resulting in a significantly more intense coagulant response to Xa/PCPS does not preclude inactivation of factors Va and VIIIa and the full expression of the fibrinolytic response. We conclude further that after thrombin generation in vivo, protein C activation is not a prerequisite for the promotion of the fibrinolytic response previously observed, and that the inactivation of factors Va/VIIIa may be mediated by enzymes other than activated protein C. The reduction in alpha 2-antiplasmin levels in association with increased tissue plasminogen activator activity suggests that plasmin is a likely candidate.
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PMID:Anticoagulant and fibrinolytic activities are promoted, not retarded, in vivo after thrombin generation in the presence of a monoclonal antibody that inhibits activation of protein C. 155 68

Activated factor V (Va) serves as an essential protein cofactor for the conversion of prothrombin to thrombin by factor Xa. Analysis of the factor V cDNA indicates that the protein contains several types of internal repeats with the following domain structure: A1-A2-B-A3-C1-C2. In this report we describe the isolation and characterization of genomic DNA coding for human factor V. The factor V gene contains 25 exons which range in size from 72 to 2820 bp. The structure of the gene for factor V is similar to the previously characterized gene for factor VIII. Based on the aligned amino acid sequences of the two proteins, 21 of the 24 intron-exon boundaries in the factor V gene occur at the same location as in the factor VIII gene. In both genes, the junctions of the A1-A2 and A2-A3 domains are each encoded by a single exon. In contrast, the boundaries between domains A3-C1 and C1-C2 occur at intron-exon boundaries, which is consistent with evolution through domain duplication and exon shuffling. The connecting region or B domain of factor V is encoded by a single large exon of 2820 bp. The corresponding exon of the factor VIII gene contains 3106 bp. The 5' and 3' ends of both of these exons encode sequences homologous to the carboxyl-terminal end of domain A2 and the amino-terminal end of domain A3 in ceruloplasmin. There is otherwise no homology between the B domain exons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structure of the gene for human coagulation factor V. 156 32


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