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 effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.
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PMID:Effect of flomoxef on blood coagulation and alcohol metabolism. 178 45

The in vitro effects of zinc and magnesium salts on blood coagulation mechanism and platelet aggregation were studied on rat plasma. Addition of zinc sulphate to pooled rat plasma in a range of concentrations (0.3-1 mg/ml) caused a dose dependent significant prolongation of recalcification, prothrombin and partial thromboplastin times. These effects reached a peak after 30 minutes while the thrombin clotting time was not significantly altered and was even shortened in the presence of highest concentration of zinc tested (1 mg/ml). Incubation of thrombin with zinc sulphate (150 micrograms/ml) for up to 30 minutes did not affect significantly the action of thrombin. Incubation of the same concentrations of zinc sulphate with fibrinogen produced non clotting of fibrinogen after 0-minutes. Addition of rising concentrations of zinc sulphate to rat PRP produced inhibition of ADP-induced platelet aggregation. On the other hand, collagen-induced aggregation was insignificantly inhibited in the presence of zinc. In contrast, in vitro additions of rising concentrations of magnesium sulphate (2-5 mg/ml) to pooled rat plasma exerted no effect on recalcification time immediately after addition (0-minutes), but after 5 minutes following incubation it produced significant shortening of recalcification time in all the doses tested. The prothrombin time showed a general trend of shortening, maximal after 5-minutes incubation. The results of partial thromboplastin times revealed clotting before addition of calcium chloride. The thromboplastin time also showed progressive shortening with rising concentrations of magnesium sulphate. When thrombin solution was exposed to magnesium sulphate (2.5 mg/ml) no effect on the activity of thrombin was seen for up to 30 minutes. Fibrinogen solution similarly exposed to the same concentration of magnesium sulphate did not show any significant effect on its clottability with thrombin for up to 30 minutes. Magnesium sulphate in the range of doses tested significantly enhanced platelet aggregation of PRP in response to both ADP and collagen, and the responses observed were not dose dependent. The mechanisms underlying the effects of these two metals on blood clotting and platelet aggregation are discussed.
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PMID:In vitro effects of trace elements on blood clotting and platelet function. B--Zinc and magnesium. 180 Jun 25

In Japanese black cattle with large and long-existing hematomas, platelets was impaired in collagen aggregation function in vitro. There was no statistically significant difference from control animals in the tests of PT (prothrombin time) and PTT (partial thromboplastin time) for extrinsic and intrinsic blood coagulation system. Aside from impaired collagen aggregation function, platelets in the hematoma cattle showed the similar aggregation patterns as the normal cattle, when ADP, serotonin (5-HT), thrombin, arachidonic acid, epinephrine and ristocetin were used as agents for inducing aggregation. Decreased aggregation function as well as impaired collagen-induced release response in platelets suggested the hematoma cattle to be of storage pool disease (SPD). The impaired platelet was postulated to be a main cause of the large and long-existing hematomas. All of the hematoma cattle with impaired platelet functions had the eosinophils in peripheral blood of which granules were fewer and larger than normal ones. These large eosinophil granules were peroxidase positive and periodic acid Schiff (PAS) staining negative as typical eosinophil granules.
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PMID:Persistent hematomas in Japanese black cattle with impaired platelet aggregation function and large granule eosinophils. 183 Jul 60

There are many factors influencing the growth of the fetus. Since these factors have complex interrelations, they are difficult to clarify. The authors studied the effects of blood coagulation and fibrinolysis on the growth of the fetus during pregnancy, especially from the 2nd trimester into the 3rd trimester. The subjects were 86 normal pregnant women, and the subjects of study were blood coagulation, fibrinolysis activity of the mother, and estimated fetal birth weight after the 28th (2nd trimester) and 36th weeks of gestation (3rd trimester) in each case. 1. Changes in blood coagulation activity and fibrinolysis varied from the 2nd trimester into the 3rd trimester. The percentage of cases showing lowered platelets was 68.6% of the total, and the percentages of cases with reduced platelet ADP, epinephrine, and collagen aggregation were 60.5%, 55.8%, and 51.2%, respectively. The percentages of cases showing shortened prothrombin time and activated partial thromboplastin time were 58.1% and 51.2% of the total, respectively. The percentage of cases with reduced fibrinogen was 24.4% of the total. The percentages of cases with reduced antithrombin III, plasminogen, and alpha 2-plasmin inhibitor activity were 66.3%, 55.8%, and 75.6% of the total, respectively. 2. The birth weight of babies in a group with shortened prothrombin time was 2,935.1 +/- 395.2g(n = 50, mean +/- SD), while that in a group with prolonged prothrombin time was 3,106.2 +/- 357.9g(n = 36). The estimated fetal birth weight gain from the 2nd trimester to the 3rd trimester was 1,431.6 +/- 296.5g in the former group and 1,644.5 +/- 390.5g in the latter group. The differences were significant (p less than 0.05, p less than 0.01). The birth weight of babies in a group with lowered antithrombin III activity was 2,960.1 +/- 341.3g(n = 57), and that in an acceleration group was 3,157.8 +/- 370.0g(n = 29). The estimated fetal weight gain from the 2nd trimester to the 3rd trimester was 1,477.7 +/- 281.9g in the former group and 1,637.1 +/- 390.6g in the latter group. The differences were significant (p less than 0.02, p less than 0.05). 3. The estimated fetal weight gain from the 2nd trimester to the 3rd trimester in the group showing prolongated prothrombin time and activated partial thromboplastin time in this period was significantly larger than in the group showing shortened prothrombin time and activated partial thromboplastin time (p less than 0.001). These results suggested that the changes in blood coagulation and fibrinolysis activity of mothers from the 2nd trimester to the 3rd trimester affected the growth of the fetus.
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PMID:[Blood coagulation and fibrinolysis activities during normal pregnancy and fetal growth--study based on estimated fetal body weight]. 191 80

We evaluated the effect of the RGD-containing peptide, echistatin, on thrombolysis time and acute reocclusion in a canine model of coronary thrombosis/thrombolysis. Occlusive thrombus formation was induced by electrical injury, via a stimulating electrode, to the endothelial surface of the circumflex coronary artery in the open-chest, anesthetized dog in the presence of a critical stenosis. Fifteen minutes after occlusive thrombus formation, dogs received either an intravenous infusion of vehicle (saline at 0.1 ml/min) or echistatin (15 micrograms/kg/min i.v.). Heparin was given as an initial bolus (100 U/kg i.v.) 15 min after thrombus formation and repeated at hourly intervals (50 U/kg). This dose of heparin increased activated partial thromboplastin time to 1.5- to 2.5- fold over control. Thrombolysis was induced with recombinant tissue-type plasminogen activator (tPA) at a total dose of 1 mg/kg, intravenously administered over 90 min with 10% given as an initial bolus. The vehicle-treated animals reperfused at 48 +/- 9 min with a reperfusion incidence of 60% (3/5). The echistatin-treated animals reperfused at 46 +/- 5 min with a reperfusion incidence of 100% (5/5). After stopping the tPA infusion, acute reocclusion occurred in 100% (3/3) of the vehicle-treated dogs and in only 20% (1/5) of the echistatin-treated dogs. Echistatin caused a greater than 5-fold increase in buccal mucosa bleeding time and almost completely inhibited ex vivo platelet aggregation to ADP, collagen, and U-46619. Residual thrombus wet weight, determined at the end of the experiment, was significantly lower for the echistatin group (2.1 +/- 0.2 mg) compared to the vehicle group (5.8 +/- 0.7 mg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of reocclusion following tissue type plasminogen activator-induced thrombolysis by the RGD-containing peptide, echistatin, in a canine model of coronary thrombosis. 194 98

To clarify the pathogenesis of antiphospholipid antibody (aPL) syndrome, the reactivities of anticardiolipin antibodies (aCL) in sera of patients with systemic lupus erythematosus (SLE) or other diseases to fresh, activated or destroyed blood cells were examined by the inhibition assay using an enzyme-linked immunosorbent assay. In addition, the effects of lupus anticoagulants (LA) in the patients' plasma and of immune complexes formed between LA and PL antigens on platelet aggregations were also determined. The IgG-aCL activity of patients' sera was markedly inhibited by pre-incubation with freeze-thawed blood cells, including erythrocytes (RBC), mononuclear cells (MNC) and platelets, but not fresh platelets or RBC. The aCL activity was slightly inhibited by fresh MNC, and was definitely inhibited by thrombin-activated platelets and polymorphonuclear cells (PMN) stimulated with phorbol 12-myristate 13-acetate (PMA). However, the activity was not inhibited by platelets stimulated with adenosine 5'-diphosphate (ADP; 10 microM). Twenty-two LA positive plasma and 17 LA negative plasma from patients similarly enhanced the aggregation of platelets which were obtained from healthy adults and stimulated with low concentrations of ADP (1 or 2 microM). However, such enhancement of platelet aggregation was not observed when high concentrations of ADP (5 microM) or collagen (2 micrograms/ml) were used as stimulators. In four of the 16 LA positive plasma examined, the mixture of plasma and phospholipid reagent for activated partial thromboplastin time induced platelet aggregations without the other stimulations, but the plasmas themselves did not induce such a reaction. The above results indicate that the aPL from patients do not react with intact blood cells in vitro, but they can react with activated or destroyed blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reactivities of antiphospholipid antibodies to blood cells and their effects on platelet aggregations in vitro. 212 28

Proteins of the annexin/lipocortin family act as in vitro anticoagulants by binding to anionic phospholipid vesicles. In this study, we investigated whether annexin V (placental anticoagulant protein I) would bind to human platelets. Annexin V bound to unstimulated platelets in a reversible, calcium-dependent reaction with an apparent Kd of 7 nM and 5000-8000 sites/platelet. Additional binding sites could be induced by several platelet agonists in the following order of effectiveness: A23187 greater than collagen + thrombin greater than collagen greater than thrombin. However, neither ADP nor epinephrine induced additional binding sites. Three other proteins of the annexin family (annexins II, III, and IV) competed for annexin V platelets binding sites with the same relative potencies previously observed for binding to phospholipid vesicles. Phospholipid vesicles containing phosphatidylserine completely inhibited binding of annexin V to platelets. Annexin V completely blocked binding of 125I-factor Xa to thrombin-stimulated platelets. These results support the hypothesis that phosphatidylserine exposure occurs during platelet activation and may be necessary for assembly of the prothrombinase complex on platelet membranes.
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PMID:Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets. 214 74

The functional characterization of human platelet-released factor V and its activation by factor Xa and thrombin was studied by functional assessment of cofactor activity and Western blotting analyses of platelet releasates, obtained by stimulating washed suspensions of platelets with various agonists, including collagen, collagen with ADP, and the calcium ionophore A23187. Platelet factor V was released as a partially proteolyzed molecule that was bound to platelet microparticles, irrespective of the agonist used. Radiolabeled plasma factor V was not cleaved for up to 30 min following release when added to platelets prior to stimulation, suggesting that platelet factor V was stored in a partially proteolyzed form. Released platelet factor V possessed significant cofactor activity that was increased only 2-3-fold by either factor Xa or thrombin. The factor V subunits that expressed cofactor activity were isolated and found to consist of peptides of Mr = 220,000 and 150,000. Incubation of released platelet factor V with factor Xa or thrombin yielded the same cleavage pattern, in which two peptides of Mr = 105,000 and 74,000 appeared to be electrophoretically indistinguishable from thrombin-activated plasma factor V. Under the conditions of these studies, factor Xa activated platelet-released factor V 50-100 times more effectively than thrombin. This observation may be due in part to the existence of platelet factor V in a partially proteolyzed state, or its association with platelet microparticles following platelet stimulation. These data collectively suggest that platelet-released factor V may be the foremost initiator of prothrombinase complex assembly and function during the early stages of coagulation with additional cofactor activation accomplished by factor Xa.
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PMID:Functional characterization of human platelet-released factor V and its activation by factor Xa and thrombin. 221 16

It is postulated that ADP secreted by platelets is the physiological thromboplastin which initiates the conversion of prothrombin to thrombin and hence brings about the coagulation of the blood. The experiments which led to the formulation of the hypothesis are described. Experimental work compatible with the hypothesis is outlined. The implications of the hypothesis with regard to the modern cascade theory of coagulation are discussed.
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PMID:On the coagulation of the blood: an elaboration of Lord Lister's hypothesis and the four-factor model of Morawitz. 225 76

The purpose of this study was to correlate bleeding complications during and after treatment with recombinant tissue-type plasminogen activator (rt-PA) with serial template bleeding time measurements, with ADP-induced platelet aggregation, with clinical characteristics, and with hemostatic parameters. Fifty-two of 55 consecutive patients with acute myocardial infarction and template bleeding times (Ivy method) of less than 9.5 minutes were treated with rt-PA in a total dose of 55-212 mg (mean, 109 mg) over 90 to 360 minutes (median, 240 minutes) combined with heparin. The mean bleeding time was significantly prolonged at 90 minutes (from 5.0 +/- 1.9 to 8.2 +/- 4.3 minutes, p less than 0.0001) but returned toward baseline after 4 hours (from a median of 8.0 to 7.0 minutes, p less than 0.05). Thirteen patients (25%) suffered relatively minor but spontaneous bleeding that did not correlate with age, hypertension, smoking, partial thromboplastin time, platelet count, ADP-induced platelet aggregation, steady-state rt-PA level, or extent of fibrinogen degradation. In multivariate analysis, only the 90-minute bleeding time correlated with spontaneous bleeding (p = 0.01). Prolongation of the 90-minute bleeding time to greater than or equal to 9 minutes, which occurred in 21 patients, correlated with spontaneous bleeding with a sensitivity of 69% (95% confidence interval, 39-90%) and a specificity of 69% (95% confidence interval, 52-83%). Retrospective analysis revealed that in 14 patients taking aspirin, the bleeding time at 90 minutes was significantly more prolonged (p less than 0.05) and spontaneous bleeding significantly more frequent (p less than 0.01) than in patients not taking aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between template bleeding times and spontaneous bleeding during treatment of acute myocardial infarction with recombinant tissue-type plasminogen activator. 250 11


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