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

Extradural anaesthesia is associated with lower incidences of deep vein thrombosis after total knee arthroplasty. It is not known if the type of anaesthesia influences thrombogenesis or fibrinolysis during knee surgery performed under tourniquet. We studied 31 patients allocated randomly to receive either extradural or general anaesthesia for primary unilateral total knee arthroplasty performed under tourniquet. Radial artery blood samples were obtained before surgery, during surgery with the tourniquet inflated and on deflation of the tourniquet. Plasma samples were assayed for markers of thrombin generation and fibrinolysis. Two of the circulating indices of thrombin generation, fibrinopeptide A and thrombin-antithrombin complexes, increased to a similar degree in the perioperative period in both groups. Fibrinolytic activity was similar in both groups, as measured by tissue plasminogen activator (t-PA) antigen, t-PA activity, t-PA-plasminogen activator inhibitor complexes, alpha 2-plasmin inhibitor-plasmin complexes and D-dimer. Extradural and general anaesthesia did not result in significant differences in either thrombin generation or fibrinolytic activity during total knee arthroplasty performed under tourniquet.
 ...
PMID:Comparison of extradural and general anaesthesia on the fibrinolytic response to total knee arthroplasty. 950 95

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.
 ...
PMID:Evidence against an effect of endothelin-1 on blood coagulation, fibrinolysis, and endothelial cell integrity in healthy men. 940 67

We investigated the effects of human inter-alpha-inhibitor (I alpha I) on hemodynamics, oxygenation, and coagulation parameters in a porcine model of endotoxic shock. Four groups of six animals were studied: (1) control, (2) I alpha I group receiving 30 mg/kg I alpha I over 30 min, (3) LPS group receiving 5 micrograms.kg/min Escherichia coli endotoxin over 30 min, and (4) LPS + I alpha I group receiving 30 min after endotoxin 30 mg/kg/30 min I alpha I. We measured hemodynamic and oxygenation parameters, usual coagulation markers and plasma levels of thrombin-antithrombin complexes, antithrombin III activity, plasminogen activator tissue type, plasminogen activator inhibitor type 1, von Willebrand factor, tumor necrosis factor-alpha, and I alpha I at baseline and at 30, 60, 90, 120, 180, 240, and 300 min. In the I alpha I group, plasma I alpha I levels reached 447 +/- 23 mg/L just after injection and 287 +/- 39 mg/L at 300 min. I alpha I half-life was 7.3 +/- 1.9 h. In the IPS + I alpha I group, I alpha I plasma levels decreased more rapidly, reaching 260 mg/L at 300 min. Compared with the LPS group, administration of I alpha I normalized the mean arterial pressure and cardiac index, improved the LPS-induced pulmonary hypertension, and resulted in the blunted increase in blood lactate and oxygen extraction ratio. A significant decrease in thrombin-antithrombin complexes and plasminogen activator inhibitor type 1 levels were observed. There was no significant difference in plasma tumor necrosis factor-alpha levels. We concluded that in this hypodynamic model of endotoxin shock, I alpha I administration resulted in a marked improvement in the hemodynamic, oxygenation, and coagulation parameters.
 ...
PMID:Effects of inter-alpha-inhibitor in experimental endotoxic shock and disseminated intravascular coagulation. 941 62

In patients with sepsis and septic shock, both coagulation and fibrinolysis are activated frequently leading to the syndrome of diffuse intravascular coagulation (DIC). The different mechanisms leading to abnormalities in coagulation and fibrinolysis are discussed in detail. The coagulation and fibrinolytic system appear to be influenced by the septic process largely independently, leading to a procoagulant imbalance between these systems. Coagulation is initiated by mediator-induced expression of tissue factor and is associated with consumption of the natural coagulation inhibitors antithrombin III, protein C, and protein S. As a result, high plasma levels of thrombin-antithrombin complex (TAT) can be found. The effects on fibrinolysis are dominated by (highly) increased levels of plasminogen activator inhibitor type 1 (PAI-1), leading to inadequate fibrinolysis. Although levels of plasminogen activator antigen are increased, its activity is almost completely inhibited by PAI-1. The resulting effects predispose to a procoagulant state, with widespread fibrin deposition, which may be an important mechanism contributing to multiple organ failure. A thorough understanding of the pathophysiological mechanisms underlying the DIC-syndrome is a prerequisite for a rational approach and future therapy for this severe complication of sepsis.
 ...
PMID:Derangements of coagulation and fibrinolysis in critically ill patients with sepsis and septic shock. 951 78

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.
 ...
PMID:Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction. 955 72

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.
 ...
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.
 ...
PMID:Adjuvant antiestrogen treatment with tamoxifen in postmenopausal women with breast cancer: a longitudinal study of blood coagulation and fibrinolysis. 980 22

A limitation of current fibrinolytic drugs is the procoagulant activity induced by their administration. TNK is a mutant of tissue plasminogen activator (t-PA) with high fibrin specificity, resistance to plasminogen activator inhibitor-1 and slow plasma clearance, which is administered in a single intravenous bolus. In this study we investigated the procoagulant effect of TNK-t-PA compared to streptokinase, rt-PA or no thrombolysis. Twenty-nine patients with acute myocardial infarction, treated within 6 hours of symptom onset with 1.5 MU streptokinase over 1 hour (n = 12), 100 mg rt-PA in 1.5 hours (n = 12) or 30-40 mg TNK-t-PA in 15 s (n = 5), were studied and compared to 7 patients with contraindications to thrombolysis (control group). All patients received a similar i.v. heparin regimen for at least 24 hours. Blood samples were drawn before the start of treatment (time 0) and after 2 hours. Thrombin formation was assessed as plasma concentrations of thrombin-antithrombin complex (TAT). The four patient groups did not differ significantly in age, sex, time to treatment, infarct location, and TAT values at time 0 (mean value +/- standard error of the mean 9 +/- 2 micrograms/l). Mean TAT levels at 2 hours were 26 +/- 6 micrograms/l in streptokinase treated patients (p = 0.005 vs time 0), 21 +/- 4 micrograms/l in rt-PA treated patients (p < 0.05 vs time 0), 5 +/- 0.6 micrograms/l in TNK treated patients, and 4 +/- 0.4 micrograms/l in controls (NS vs time 0 for TNK and controls). In conclusion, our data suggest that, in patients with acute myocardial infarction, bolus TNK-t-PA, unlike streptokinase or rt-PA infusions, is devoid of procoagulant effects, evaluated 2 hours after its administration.
 ...
PMID:[The absence of a procoagulant effect after TNK-t-PA: a comparison with streptokinase and rt-PA]. 992 87

Recently, human umbilical vein endothelial cells (HUVEC) have been shown to express functional high-affinity receptors for factor Xa, which may be of importance in the regulation of coagulation and homeostasis of the vascular wall. In this paper, we demonstrate that when added to cultured HUVEC, factor Xa was a potent mitogen, stimulating an increase in cell number at a 0.3 to 100 nM concentration. The same doses of factor Xa also increased intracellular free calcium levels and phosphoinositide turnover. When added to confluent HUVEC, factor Xa induced the expression of tissue factor and the release of tissue-type plasminogen activator and plasminogen activator inhibitor-1 without affecting urokinase expression. Indirect (antithrombin-pentasaccharide) and direct (DX9065) inhibitors of factor Xa affected all these activities of factor Xa in a dose-dependent manner. Taken together, these data show that the activities induced by factor Xa on HUVEC were dependent on its catalytic activity and could be inhibited by both direct and indirect factor Xa inhibitors.
 ...
PMID:Activation of human vascular endothelial cells by factor Xa: effect of specific inhibitors. 1003 44

We investigated soluble, thrombin-related material in arterial thrombi and venous plasma during catheter-directed thrombolysis with alteplase. Arteriography was performed before thrombolysis and 0.5, 3, 10 and 24 h after the onset of treatment in six patients with (sub)acute lower extremity ischaemia caused by native artery or bypass occlusion. Samples were collected simultaneously from the thrombus and venous blood. After adding inhibitors of thrombin and plasmin, the centrifuged samples were assayed for prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT) and fibrinopeptide A (FPA). Levels of F1+2, TAT and FPA were extremely elevated in the thrombus-related samples before the blood flow was re-established (at 0 and 0.5 h) in all five successfully treated patients. In comparison, venous plasma levels of F1+2, TAT and FPA were moderately elevated, and reached a maximum at 3 h. In conclusion, material aspirated from lysing human thrombi formed in vivo contains large amounts of F1+2, TAT and FPA, but our methods prevented us from detecting enzymatically active thrombin.
 ...
PMID:Soluble, thrombin-related material in arterial thrombi and plasma studied during catheter-directed intra-arterial thrombolysis. 1019 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>