Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of an array of preclinical experimental results, it has been widely assumed that endothelin-1 (ET-1) may affect blood coagulation, fibrinolysis, and endothelial cell function, thereby playing a pathophysiological role in various cardiovascular diseases in humans. However, confirmation of this assumption is still lacking. ET-1 or placebo was administered intravenously to 12 healthy volunteers in a prospective, randomized, double-blind, crossover trial. Pathophysiologically relevant concentrations of ET-1 (an approximate threefold increase of normal blood levels) causing hemodynamic effects were reached by continuous intravenous infusion for 6 hours. Components of the coagulation (thrombin-antithrombin complexes, prothrombin fragment F1 + 2, activated factor VII, and factor VII antigen) and fibrinolytic (fibrin split product D-dimer, plasmin-plasmin inhibitor complex, tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor-1) systems and markers of endothelial cell perturbation/dysfunction (von Willebrand factor and thrombomodulin) were measured before the start of infusion and after 2, 6, 12, and 24 hours. Comparing changes in the plasma concentrations of these parameters during and after infusion of ET-1 and placebo, we found no specific effects of ET-1. In contrast to previous reports from preclinical experiments, ET-1 does not appear to affect coagulation or fibrinolysis, nor does this peptide induce relevant endothelial cell perturbations in humans.
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PMID:Evidence against an effect of endothelin-1 on blood coagulation, fibrinolysis, and endothelial cell integrity in healthy men. 940 67

Activated protein C (APC) is a potent physiologic anticoagulant with profibrinolytic properties, and has been shown to prevent thrombosis in different experimental models. We investigated the effect of human APC on thrombin-induced thromboembolism in mice, a model of acute intravascular fibrin deposition leading to death within minutes. APC given intravenously (i.v.) as a bolus 2 min before thrombin challenge (1,250 U/kg) reduced mortality in a dose-dependent manner despite the lack of thrombin inhibitor activity. Significant inhibition of thrombin-induced death was observed at the dose of 0.05 mg/kg, and maximal protection was obtained with 2 mg/kg (> 85% reduction in mortality rate). Histology of lung tissue revealed that APC treatment (2 mg/kg) reduced significantly vascular occlusion rate (from 89.2 to 46.6%, P < 0.01). The protective effect of APC was due to the inhibition of endogenous thrombin formation as indicated by the fact that (a) the injection of human thrombin caused a marked decrease in the coagulation factors of the intrinsic and common pathways (but not of Factor VII), suggesting the activation of blood clotting via the contact system; (b) APC pretreatment reduced markedly prothrombin consumption; (c) the lethal effect of thrombin was almost abolished when the animals were made deficient in vitamin K-dependent factors by warfarin treatment, and could be restored only by doubling the dose of thrombin, indicating that the generation of endogenous thrombin contributes significantly to death; and (d) APC failed to protect warfarin-treated animals, in which mortality is entirely due to injected thrombin, even after protein S supplementation. Other results suggest that APC protects from thrombin-induced thromboembolism by rendering the formed fibrin more susceptible to plasmin degradation rather than by reducing fibrin formation: in thrombin-treated mice, fibrinogen consumption was not inhibited by APC; and inhibition of endogenous fibrinolysis by epsilon-aminocaproic or tranexamic acid resulted in a significant reduction of the protective effect of APC. Since APC did not enhance plasma fibrinolytic activity, as assessed by the measurement of plasminogen activator (PA) or PA inhibitor (PAI) activities, PAI-1 antigen, or 125I-fibrin degrading activity, we speculate that the inhibition of additional (endogenous) thrombin formation by APC interrupts thrombin-dependent mechanisms that make fibrin clots more resistant to lysis, so that the intravascular deposited fibrin can be removed more rapidly by the endogenous fibrinolytic system.
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PMID:Activated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein c reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation. 944 1

To examine the relationship between exercise intensity and activation of coagulation and fibrinolysis, we measured markers of thrombin, fibrin, and plasmin formation in 12 male subjects (mean 24+/-4 yr (SD)) before and after running on a treadmill for 1 h at two different intensities corresponding to moderate (82% maximal heart rate (HR), 68% VO2max) and very heavy (94% maximal HR, 83% VO2max) exercise. During moderate exercise plasma levels of tissue plasminogen activator (t-PA) antigen rose from 3.7+/-0.5 (mean+/-SE) to 14.6+/-1.8 ng x mL[-1] (P < 0.01) and of plasmin-alpha-antiplasmin (PAP) complexes from 2.1+/-0.3 to 4.2+/-0.7 nmol x L[-1] (P < 0.01), whereas prothrombin fragment 1+2 (PTF1+2), thrombin-antithrombin III (TAT) complexes and fibrinopeptide A (FPA) did not change significantly. In response to very heavy exercise, mean plasma levels of t-PA antigen and PAP complexes exceeded the upper limit of normal values 2.5- (P < 0.01) and two-fold (P < 0.01), respectively, while significant increases of plasma levels of PTF1+2 (P < 0.01), TAT (P < 0.05), and FPA (P < 0.01) occurred within the range of normal. We conclude that in healthy young individuals, exercise-induced activation of coagulation is well balanced by activation of the fibrinolytic system, since moderate exercise results in increased plasmin formation only, while at very heavy exercise generation of plasmin seems to exceed that of thrombin and fibrin.
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PMID:Coagulation and fibrinolysis after moderate and very heavy exercise in healthy male subjects. 950 53

Recent clinical studies comparing accelerated versus bolus administration of alteplase tissue plasminogen activator (t-PA) suggest similar thrombolytic efficacy, but reveal higher bleeding complications among older patients during the double-bolus regimen. The objective of the present study was to characterize the hemostatic profile of t-PA administered as double-bolus doses of 50 mg, at intervals of 30 minutes. Among 50 patients with acute myocardial infarction treated by double-bolus t-PA thrombolysis, coagulation and fibrinolysis parameters, as well as t-PA levels, were monitored. Monitored t-PA levels peaked at 5 and 35 minutes and were detectable within the therapeutic range even after 90 minutes. Marked systemic fibrinolytic activation was indicated by 75% depletion of both plasminogen and fibrinogen, as well as by 19-fold and 300-fold increases of fibrin degradation and fibrinogen degradation products. Plasminogen-activator inhibitor activity was completely suppressed. Pronounced procoagulant activation was reflected by a 3.4-fold increase of both factor XIIa and prothrombin fragment 1+2, and by a threefold increase of thrombin-antithrombin complex. Independent of t-PA weight dosage, fibrinolytic activation was more pronounced among older patients (> or = 63 years). We conclude that t-PA after bolus administration has a long half-life. Double-bolus regimen leads to a long-lasting systemic fibrinolytic state, which is even more remarkable among older patients--a fact that may explain the higher bleeding complications reported for this age group.
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PMID:Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction. 955 72

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.
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PMID:Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. 957 11

Trimeresurus stejnegeri venom which contains TSV-PA (a specific plasminogen activator sharing 60-70% sequence homology with venom fibrinogen-clotting enzymes), also possesses fibrinogen-clotting activity in vitro. A fibrinogen-clotting enzyme (stejnobin) has been purified to homogeneity by gel filtration and ion-exchange chromatography on a Mono-Q column. It is a single-chain glycoprotein with a mol. wt of 44,000. The NH2-terminal amino acid sequence of stejnobin shows great homology with venom fibrinogen-clotting enzymes and TSV-PA. Like TSV-PA, stejnobin was able to hydrolyse several chromogenic substrates. Comparative study of substrate specificities of stejnobin and other venom proteases purified in our laboratory was carried out on five chromogenic substrates. Stejnobin clotted human fibrinogen with a specific activity of 122 NIH thrombin-equivalent units/mg protein. However, stejnobin did not act on other blood coagulation factors, such as factor X, prothrombin and plasminogen. Diisopropyl fluorophosphate and phenylmethanesulfonyl fluoride inhibited its activity, whereas ethylenediamine tetracetic acid had no effect on it, indicating that it is a serine protease. Although stejnobin showed strong immunological cross-reaction with polyclonal antibodies raised against TSV-PA, it was interesting to observe that, unlike the case of TSV-PA, these antibodies did not inhibit the amidolytic and fibrinogen-clotting activities of stejnobin.
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PMID:Characterization of a fibrinogen-clotting enzyme from Trimeresurus stejnegeri venom, and comparative study with other venom proteases. 960 87

The effects of two progestogen-only pills containing either 75 microgram desogestrel (DSG) or 30 microgram levonorgestrel (LNG) on hemostasis were investigated in a double-blind, randomized, controlled study of seven treatment cycles in 78 healthy women. DSG reduced factor VII activity (p < 0.05) and prothrombin fragment 1+2 (p < 0.05) and increased protein S (p < 0.001). LNG reduced factor VII activity (p < 0.01) and plasminogen activity (p < 0.01) and increased tissue-plasminogen activator (t-PA) (p < 0.05). At the end of the post-treatment cycle with DSG, protein S (p < 0.01) and t-PA (p < 0.05) were increased and plasminogen activity was decreased (p < 0.05), whereas with LNG, t-PA was increased (p < 0.001) and prothrombin fragment 1+2 (p < 0.05) and plasminogen activity (p < 0.001) were decreased. Between-group comparisons revealed higher values for DSG regarding the anticoagulatory parameter protein S at cycle 7 (p < 0.01) and post-treatment assessments (p < 0.05), and the fibrinolytic parameter plasmin-antiplasmin complex was higher with DSG at cycle 7 (p < 0.05) and at post-treatment (p < 0.05). Both preparations had comparable and potentially favorable effects of hemostasis, and may offer suitable hormonal contraception to women with a personal or family history of venous thromboembolic diseases.
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PMID:A randomized controlled double-blind study of the effects on hemostasis of two progestogen-only pills containing 75 microgram desogestrel or 30 microgram levonorgestrel. 969 98

We review laboratory tests that evaluate thrombogenesis during acute coronary syndromes. These tests have been found to be valuable research tools in more clearly understanding the pathophysiology of acute coronary syndromes. In particular, we describe tissue factor, tissue factor pathway inhibitor, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrinopeptide A, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), t-PA-PAI complex, Bbeta 15-42-related peptides, fibrinogen degradation products, fibrin degradation products, D-dimer, platelet factor 4, beta-thromboglobulin, 5-hydroxytryptamine, thromboxane B2, prostacyclin, endothelin, angiotensin-converting enzyme, soluble thrombomodulin, C1-esterase inhibitor, anaphylotoxins C3a, C4a, and C5a, bradykinin, tumor necrosis factor, leukotriene C4, platelet activating factor, anti-phospholipid antibody, and von Willebrand factor. Some of these tests may prove to be useful in clinical diagnosis and management of acute coronary syndromes. Clinical outcome studies are needed to determine which tests may be cost effective and medically useful.
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PMID:Useful laboratory tests for studying thrombogenesis in acute cardiac syndromes. 970 94

Potential effects of tamoxifen therapy on blood coagulation and fibrinolysis were investigated in women with breast cancer. We studied 14 parameters of hemostasis in 19 postmenopausal women receiving 20 mg tamoxifen/day as an adjuvant treatment. Blood sampling was done before and after the 1st, 3rd, and 6th month of treatment. Pretreatment values of procoagulation, anticoagulation, plasminogen, and plasminogen activator inhibitor were found within the reference range, whereas tissue-plasminogen activator, fibrin degradation products, and prothrombin-fragment 1+2 were elevated. On therapy an initial decrease of all measured parameters was observed. The effect was pronounced in coagulation inhibitors (antithrombin III, protein C and S). No pathological values (below 60%) were observed. No further effects were found during the 3rd and 6th month of treatment. Our data indicate that the decrease of hemostatic parameters during the initial phase of tamoxifen treatment is due to the timing of blood collection, which took place no more than 14 days after surgery. The reduction of coagulation inhibitors was not associated with pathological values. No cumulative effects were seen during tamoxifen therapy. The decrease was not associated with a concomittant increase of in vivo coagulation markers (prothrombin-fragment 1+2, thrombin-antithrombin-complex, fibrin degradation products). Therefore our results are likely to reflect only the resolution of postoperative activation and do not translate into a drug related thrombogenic effect.
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PMID:Adjuvant antiestrogen treatment with tamoxifen in postmenopausal women with breast cancer: a longitudinal study of blood coagulation and fibrinolysis. 980 22

Twenty patients with recently recognised bronchial asthma and 22 age and sex-matched healthy control subjects were studied. In both groups the activated partial thromboplastin time (APTT), prothrombin ratio (INR), fibrinogen, euglobulin lysis time (ELT), platelet number and platelet adhesion and aggregation, tissue plasminogen activator antigen (t-PA Ag) and activity of plasminogen activator inhibitor (PAI-1) were tested and compared. Statistically significant differences between asthmatic and control groups concerning adhesion, aggregation, APTT and ELT were found. In asthmatic group after 14 days of prednisone administration in a dose of 20 mg/d statistically significant (p < 0.05) shortening of APTT, and a significant increase of adhesion, aggregation and PAI-1 activity were found. These results suggest that in asthmatic patients after prednisone treatment platelet activity appeared in a form of intensification of adhesion and of aggregation degree, also the activity of PAI-1 probably of the platelet origin increased.
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PMID:[Changes in platelet function, activated partial thromboplastin time and plasminogen activator inhibitor in patients with bronchial asthma after prednisone treatment]. 985 61


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