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)

The prevalence of subclinical coagulation abnormalities greatly differs in the various studies due to selection of patients and differences in study design. We performed coagulation studies in 69 consecutive patients with primary untreated cancer of various origin. The control group consisted of 42 sex and age matched healthy volunteers. Plasma coagulation tests included thrombin-antithrombin-III-complex (TAT), plasmin-alpha 2-antiplasmin-complex (PAP) and tissue-plasminogen-activator-antigen (t-PA-ag). These tests were performed once, prior to any anti-cancer treatment. We evaluated if activation of the coagulation system (elevated TAT-complexes) and the fibrinolytic system (elevated PAP-complexes and t-PA-ag) correlated with the tumor-type or the extent of the tumor. To document clinical manifest haemorrhage or thromboembolic disease (TED) we performed a 6 months follow-up study. In 8 patients (12%) and in 3 control subjects (7%) an elevated TAT-complex level was observed (this difference is not significant). An increased plasma level of PAP-complex was seen in 8 patients (12%) versus none in the control group (p less than 0.05). In one patient both TAT and PAP-complex concentrations were elevated. Consequently, 15 of the 69 patients (22%) showed activation of the coagulation and/or fibrinolytic system. Fibrinolysis seems to be enhanced in a subset of cancer patients in contrast to blood coagulation. In 10 patients (14%) we found raised t-PA-ag levels. Three patients had both elevated levels of PAP-complex and t-PA-ag. These findings suggest that in a minority of patients increased PAP-complex levels may be a result of t-PA induced plasminogen activation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Low prevalence of coagulation and fibrinolytic activation in patients with primary untreated cancer. 171 Aug 32

Sclerotherapy of bleeding esophageal varices in liver cirrhotics is a common procedure, but little is known about the possible entry of sclerosants into the systemic circulation. We injected a mixture of thrombin, sodium tetradecyl, and cefazolin and studied the effect of this sclerosant on selected hemostasis parameters. Twenty-four patients with liver cirrhosis (Child's Classification C) were studied 29 times. Blood samples were drawn before and immediately after the injection of the sclerosant. In seven patients we collected a sample 30 minutes and 24 hours after treatment. Before injection, almost all patients had elevated D-dimer, t-PA and PAI-1 levels. Fibrinogen, antithrombin, alpha-2 antiplasmin, and protein C were decreased. Only thrombin/antithrombin III complex (TAT) levels were within normal ranges. Immediately after the injection, TAT, D-dimer, and t-PA levels rose significantly (P less than 0.001, P less than 0.01, P less than 0.001), PAI-1 and PC levels decreased (P less than 0.01), while antithrombin, alpha-2 antiplasmin, and fibrinogen concentrations were unchanged. TAT and D-dimer levels were still elevated after 24 hours (P less than 0.05). These data indicate that thrombin entered the systemic circulation (elevated TAT) and that the hemostasis system was briefly systemically activated (elevated D-dimer). In spite of these changes in the hemostasis system, clinically there were no detectable thrombotic or hemorrhagic complications.
 ...
PMID:Hemostasis activation during esophageal variceal sclerotherapy with thrombin in cirrhotics. 171

Plasminogen activator inhibitor 1 (PAI-1) is the fast-acting inhibitor of both tissue-type and urokinase-type plasminogen activators (t-PA, u-PA) and is an essential regulatory protein of the fibrinolytic system. In the presence of either the protein vitronectin or the glycosaminoglycan heparin, PAI-1 is also an efficient inhibitor of thrombin. To assess whether these cofactors turn PAI-1 into a general protease inhibitor or whether their influence is restricted to thrombin, the second-order association rate constants between PAI-1 and the human plasma proteases t-PA, u-PA, plasmin, thrombin, Factor Xa (FXa), and Factor XIIa (FXIIa) in the absence and in the presence of either vitronectin or heparin are determined. In addition, the role of the PAI-1 reactive site P3 to P3' residues for the specificity of inhibition was studied by using PAI-1 reactive site mutants. Our results show that: (1) Heparin exclusively increases the rate of inhibition of thrombin by PAI-1, whereas in the presence of heparin the rate of inhibition of the other proteases is not altered; (2) Vitronectin is an obligatory cofactor for the inhibition of thrombin by PAI-1. In addition, vitronectin moderately increases the rate of inhibition by PAI-1 of u-PA and of plasmin, but does not alter the rate of inhibition of t-PA, FXa, or FXIIa; (3) Apart from the important role of the P1 residue, no consensus can be presented on the nature of other residues within the P3 to P3' region with regard to target protease specificity.
 ...
PMID:On the target specificity of plasminogen activator inhibitor 1: the role of heparin, vitronectin, and the reactive site. 171 20

In 11 healthy young subjects, the plasma concentrations of the thrombin-antithrombin III complex, fibrinopeptide A, tissue-plasminogen activator, complement fragments C3a and C4a, and histamine were measured before and after a graded maximal bicycle exercise test. The analyses were carried out 30 min before and immediately before exercise, immediately after exercise, and 30 and 60 min later. All post-exercise values were corrected for plasma volume changes, which were calculated from hematocrit and hemoglobin values. Immediately post-exercise, thrombin-antithrombin III, tissue-plasminogen activator, complement fragments C3a and C4a, and histamine were all significantly elevated (p less than 0.01), compared with the pre-exercise values; 30 and 60 min later the values normalized and significant differences from the pre-exercise values could no longer be measured. Fibrinopeptide A did not change significantly after exercise. The present results provide evidence for a simultaneous activation of coagulation, fibrinolysis, and complement system as well as for a release of histamine after a short maximal exercise.
 ...
PMID:Effect of a short maximal physical exercise on coagulation, fibrinolysis, and complement system. 171 17

In a prospective randomized study heptest, thrombin-antithrombin complexes (TAT), D-dimer, and t-PA:ag were analysed pre- and postoperatively in 206 consecutive patients undergoing hip arthroplasty during thromboprophylaxis with either a LMW heparin (Enoxaparin) or Dextran 70. Deep vein thrombosis (DVT) developed in 6 of 102 (6%) Enoxaparin and in 21 of 104 (20%) Dextran patients diagnosed by bilateral phelobography. In the Enoxaparin group heptest showed a significant increase from the pre- to the postoperative level opposed to a significant decrease in the Dextran group. Postoperative levels of TAT, D-dimer, and t-PA:ag were significantly increased in both groups, however, TAT was significantly higher in patients in the Dextran group than in the Enoxaparin patients. D-dimer was significantly higher in Dextran patients with DVT postoperatively compared with patients without DVT. No differences concerning TAT or t-PA:ag were observed between patients with and without DVT in any of the groups.
 ...
PMID:Components of coagulation and fibrinolysis during thrombosis prophylaxis with a low molecular weight heparin (Enoxaparin) versus Dextran 70 in hip arthroplasty. 171 55

We studied the quantitative changes of hemostatic molecular markers with time during the course of disseminated intravascular coagulation (DIC) induced by endoscopic embolization using thrombin for esophageal varices in nine patients with liver cirrhosis. The plasma levels of D-dimer, a product of plasmin degradation of cross-linked fibrin, and thrombin-antithrombin-III complex (TAT) were significantly higher in patients before treatment when compared with 60 healthy individuals. The plasma levels of TAT, D-dimer, and plasmin alpha 2-plasmin inhibitor complex (PIC) increased significantly 5-15 min after thrombin injection into the varices, earlier than the changes of conventional coagulofibrinolytic factors, reached a maximum level after 180 min, and started to decline after 1 day. Although the plasma PIC level returned to normal after 7 days, both TAT and D-dimer were still above the pretreatment level. Although there was no change in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) increased significantly after 5 min. The plasma level of plasminogen activator inhibitor type 1 (PAI-1) showed only a slight elevation after treatment. We propose that the hemostatic molecular markers TAT, D-dimer, and PIC are suitable for the early diagnosis of DIC after endoscopic embolization using thrombin in patients with liver cirrhosis and that the increase of PAI-1 is too small for the regulation of fibrinolysis due to t-PA in DIC occurring in liver cirrhosis.
 ...
PMID:Significance of hemostatic molecular markers during disseminated intravascular coagulation in patients with liver cirrhosis treated by endoscopic embolization for esophageal varices. 171 8

Orthotopic liver transplantation (OLT) is frequently associated with systemic fibrinogenolysis and diffuse bleeding. At present antifibrinolytic treatment has not been initiated routinely in OLT. Therefore the influence of high dose aprotinin in OLT (2 million kallikrein inactivator units (KIU) given after induction of anesthesia followed by a 500,000 KIU/h infusion throughout the operation) on intraoperative blood loss and fibrinolysis was studied in 25 patients compared to 25 patients without aprotinin. The incidence of fibrinolysis shown in thrombelastography was 72% in the control group versus 16% in the aprotinin group. Oozing after reperfusion of the graft caused by severe fibrinolysis defined as a clot lysis index below 15% was only observed in the control group (42.8%). In contrast no significant difference was found between the groups in the course of fibrin and fibrinogen degradation product levels (FbDP, FgDP) although the mean concentrations of both parameters were evidently lower in the aprotinin treated patients. Levels of tissue-type plasminogen activator (t-PA) activity were initially high in both groups and peaked during and after the anhepatic period. After aprotinin there was a trend of lower t-PA levels which reached significance at the time of reperfusion (p less than 0.02). In both groups the course of thrombin antithrombin complex was in line with the variations of FbDP and FgDP. No correlation between thrombin formation and t-PA activity was found. Mean homologous blood requirement was reduced by 50% (5.6 +/- 4.0 vs. 11.2 +/- 8.6 units, p less than 0.005). The blood saving effect was more pronounced in the postanhepatic period (p less than 0.000001). In conclusion high dose aprotinin inhibits hyperfibrinolysis and reduces intraoperative homologous blood requirement. Therefore its routine use in OLT is recommended.
 ...
PMID:The use of high dose aprotinin in liver transplantation: the influence on fibrinolysis and blood loss. 172 Feb 62

Vitronectin endows plasminogen activator inhibitor 1 (PAI-1), the fast-acting inhibitor of both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), with additional thrombin inhibitory properties. In view of the apparent association between PAI-1 and vitronectin in the endothelial cell matrix (ECM), we analyzed the interaction between PAI-1 and thrombin in this environment. Upon incubating 125I-labeled alpha-thrombin with endothelial cell matrix (ECM), the protease formed SDS-stable complexes exclusively with PAI-1, with subsequent release of these complexes into the supernatant. Vitronectin was required as a cofactor for the association between PAI-1 and thrombin in ECM. Metabolic labeling of endothelial cell proteins, followed by incubation of ECM with t-PA, u-PA, or thrombin, indicated that all three proteases depleted PAI-1 from ECM by complex formation and proteolytic cleavage. Proteolytically inactive thrombin as well as anticoagulant thrombin, i.e., thrombin in complex with its endothelial cell surface receptor thrombomodulin, did not neutralize PAI-1, emphasizing that the procoagulant moiety of thrombin is required for a functional interaction with PAI-1. A physiological implication of our findings may be related to the mutual neutralization of both PAI-1 and thrombin, providing a new link between plasminogen activation and the coagulation system. Evidence is provided that in ECM, procoagulant thrombin may promote plasminogen activator activity by inactivating PAI-1.
 ...
PMID:Thrombin neutralizes plasminogen activator inhibitor 1 (PAI-1) that is complexed with vitronectin in the endothelial cell matrix. 172 12

Both augmentation of thrombin activity and activation of platelets have been reported to accompany administration of plasminogen activators in vivo. To determine whether the platelet activation is a consequence or a cause of the procoagulant effects, we assessed the effects of t-PA on spontaneous activation and aggregation of platelets and on clotting in recalcified human whole blood. Spontaneous activation of platelets occurred in the stirred samples 8.9 +/- 2 minutes (n = 5) after recalcification. Aggregation and clotting followed immediately afterward. Activation, aggregation and clotting were accelerated in a dose-dependent manner by 3 minutes of preincubation with t-PA (2-30 micrograms/ml) before recalcification. The procoagulant effect of t-PA (5 micrograms/ml) was abolished by concomitant incubation with hirudin (0.5 nM) or aprotinin (200 KIU/ml) consistent with the hypothesis of plasmin-mediated evolution of thrombin being responsible for the procoagulant effect. However, platelets could be activated independently by other agonists (collagen, 3 micrograms/ml; and ADP, 25 microM) in the presence of hirudin. Despite the procoagulant effect of t-PA, aggregation to collagen (2-5 micrograms/ml) and PAF (0.9 microM) was diminished in samples incubated with t-PA for 30 minutes (37 degrees C). Fibrinogen degradation products elaborated during this interval (25.6 micrograms/ml; n = 3) were responsible for this anti-aggregatory effect. The results indicate that platelet activation in recalcified whole blood depends on procoagulant effects of t-PA.
 ...
PMID:The dependence of activation of platelets by a plasminogen activator on the evolution of thrombin activity. 172 1

Protein C inhibitor (PCI) is a heparin-dependent serpin present in a native form in plasma at concentrations of 5 micrograms/mL. In vitro, PCI inhibits activated protein C (APC), thrombin, plasma kallikrein (KK) and urokinase-(uPA) and tissue-type plasminogen activator (tPA), and we have shown in vivo inhibition of APC, uPA and KK by PCI. In order to further characterize the physiological role of PCI, we have measured the level of PCI in several biological fluids. PCI antigen was assayed by ELISA and PCI activity was measured by its capability to form complexes with APC in the presence of heparin. Seminal plasma from voluntary donors had PCI levels (160 +/- 20 micrograms/mL, mean +/- SD) about 30 or 40 times higher than those found in blood plasma. Patients under a fertilization program had significantly reduced PCI seminal levels (110 +/- 35 micrograms/mL). Seminal plasma PCI retained about 45% of its activity immediately after ejaculation, and the activity rapidly decreased following incubation of seminal plasma at 37 degrees C, in parallel with the appearance of complexes of PCI with prostate-specific antigen (PSA). PCI was present in seminal vesicle secretion, obtained by autopsy, at concentration similar to that observed in semen, was mostly active and was not inactivated by incubation of secretion at 37 degrees C. The mean functional and antigen levels of PCI in urine from normal donors were 0.58 and 0.25 micrograms/mL, respectively, whereas in saliva these levels were 20 and 0.8 ng/mL, respectively. Amniotic fluid contained PCI antigen levels of 2.1 +/- 0.2 microgram/mL. These results show that PCI is secreted in the seminal vesicles in a functional form, and suggest that PSA, a major secretory component of the prostate, is responsible for its inactivation. They also suggest a physiological role of PCI in reproduction, and show that PCI is present in various biological fluids.
 ...
PMID:Functionally active protein C inhibitor/plasminogen activator inhibitor-3 (PCI/PAI-3) is secreted in seminal vesicles, occurs at high concentrations in human seminal plasma and complexes with prostate-specific antigen. 172 27


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