Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An analysis of haemostatic variables was done in 31 prostate cancer patients treated with oestrogens (13 pts), estramustine phosphate (7 pts) or orchidectomy (11 pts) before, at about 7 weeks and 6 months of treatment. Six patients treated with either of the drugs developed venous thromboembolism or ischemic vascular disease. Already before treatment there were changes indicating some activation of blood coagulation, fibrinolysis and kallikrein systems. The drug treated group showed significant changes in several variables: i.e. increase in factor VII, plasminogen and prekallikrein but also a decrease in antithrombin and in inhibitors to the fibrinolytic and kallikrein system. Significant difference between the drug treated groups was found in circulating platelet aggregates and in kallikrein inhibiting activity. Tissue plasminogen activator capacity was significantly lower in the drug treated patients with complications than in those without. The study also showed that in addition to the assay of the tissue plasminogen activator capacity during the first weeks of therapy it might be helpful in predicting cardiovascular complications to investigate platelet aggregates, prothrombin complex, factor X, von Willebrand factor antigen, fibrinogen, antithrombin, fibrino-peptide A, and the inhibitors of fibrinolysis as well as C1-esterase inhibitor.
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PMID:Changes in blood coagulation and fibrinolysis in patients on different treatment regimens for prostatic cancer. Predictors for cardiovascular complications? 312 58

In five patients with venous thromboembolic disease treated with recombinant tissue-type plasminogen activator (rt-PA), there was a marked increase in the mean concentrations of fibrinopeptide A (from 0.6 to 5.9 nM; P less than 0.0001) and desarginine fibrinopeptide B (from 5.6 nM to 24.1 nM; P less than 0.01) 30 min after a bolus of rt-PA (0.6 mg/kg). Thrombin was unlikely to be responsible because the levels of desarginine fibrinopeptide B exceeded those of fibrinopeptide A and the changes occurred despite concomitant heparin therapy. The purpose of this study therefore, was to determine whether rt-PA directly releases the fibrinopeptides from fibrinogen. Incubation of rt-PA with heparinized plasma or purified fibrinogen resulted in time and dose-dependent release of both fibrinopeptide A and B. Contaminating thrombin was not responsible for this activity by the following criteria: the rate of rt-PA mediated fibrinopeptide B release was considerably faster than that of fibrinopeptide A, and fibrinopeptide release was unaffected by heparin, hirudin, or a monospecific antithrombin IgG. Aprotinin also had no effect on fibrinopeptide release, indicating that this activity was not plasmin mediated. Fibrinopeptide release was shown to be due to rt-PA because this activity was completely blocked by a monoclonal antibody against the enzyme. Further, the specificity of rt-PA for the thrombin cleavage sites on fibrinogen was confirmed by the demonstration that rt-PA released fibrinopeptide A or fibrinopeptide B from fibrinopeptide A or B-containing substrates, respectively. These studies thus demonstrate that (a) rt-PA releases fibrinopeptides A and B from fibrinogen thereby indicating that this enzyme is not specific for plasminogen, and (b) plasma fibrinopeptide A and desarginine fibrinopeptide B levels are not specific markers of thrombin action on fibrinogen in patients receiving rt-PA.
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PMID:Human tissue-type plasminogen activator releases fibrinopeptides A and B from fibrinogen. 314 81

Coagulation factor VIII, von Willebrand factor, antithrombin, fibrinogen, plasminogen activator capacity, and inhibitors of fibrinolysis, including a recently discovered fast inhibitor of tissue plasminogen activator, were measured three to six months after myocardial infarction in 116 male and 32 female patients aged less than 45 and in 136 age and sex matched random controls. Plasma concentrations of fibrinogen and the fast inhibitor of tissue plasminogen activator were raised in male patients (with or without correction for orosomucoid levels, blood group distribution, tobacco and alcohol consumption, and weight/height index) and plasminogen activator capacity was reduced. In female patients the concentrations of factor VIII, von Willebrand factor, the fast inhibitor of tissue plasminogen activator, alpha 2-antiplasmin, and C1 inhibitor were significantly increased. The increase in factor VIII concentrations depended strongly on a persisting inflammatory response. Multivariate analysis indicated that a combination of fibrinogen and tissue plasminogen activator inhibitor concentrations gave the best independent discrimination between male patients and controls. For female patients the best combination was von Willebrand factor and tissue plasminogen activator inhibitor. Male patients with multiple vessel atheromatosis at coronary angiography had higher fibrinogen concentrations than those with atheromatosis of a single vessel. Atheromatosis was defined as sharp-edged, plaque-like, or irregular indentations, often multiple, into the vessel lumen without features suggesting fibromuscular hyperplasia.
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PMID:Haemostatic function in myocardial infarction. 394 83

The aim of the present study was to determine whether patients with previous cerebrovascular disease have abnormalities in hemostatic functions stimulated by a 5-min venous-occlusion-test. Twenty-two patients with brain ischaemia 3-6 months previously were compared to a control group of twenty patients with non-vascular neurological diseases. Cases showed less increase in tissue plasminogen activator and fibrin degradation products than controls. There were no differences in baseline and stimulated levels of plasminogen activator inhibitor, fibrinogen degradation products, thrombin-antithrombin complex or global lysis assay (Fibriscreen). Since patients with acute cerebrovascular disease were not included, the present findings may represent either preexisting or longterm reactive fibrinolytic deficiencies, possibly predisposing to further thrombotic disease.
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PMID:Decreased fibrinolytic stimulation by a short-term venous occlusion test in patients with cerebrovascular disease. 748 39

Anabolic-androgenic steroid abuse has recently been linked with acute vascular events in athletes. To date, the relationship between steroid abuse and the potential for cardiovascular disease has been considered almost exclusively in terms of lipid metabolism. However, recent reports of thrombosis in androgen abusing athletes with no evidence of atherosclerosis suggests the hypothesis that thrombosis risk in such athletes could be mediated through androgen induced abnormalities of coagulation. To determine if anabolic-androgenic steroid abuse in weight lifters is associated with an activation of the hemostatic system we studied forty-nine weight lifters recruited through advertisements. History of androgen use or abstinence was confirmed via urine assays. Plasma was assayed for clotting and fibrinolytic activity by measuring thrombin/antithrombin complexes (TAT), prothrombin fragment 1 + 1 (F1 + 2), and D-dimers (D-di); markers of the endothelial based fibrinolytic components were assayed by measuring tissue plasminogen activator antigen (t-PA Ag) and its inhibitor (PAI-1); finally, the activity of antithrombin III, protein C, and protein S were measured. Abnormally high concentrations of TAT complexes were noted in 16% of our confirmed steroid using weight lifters compared to 6% of our confirmed nonusers (P = .01). Steroid users also demonstrated abnormally high concentrations of F1 + 2 and D-dimers when compared to nonusers (44 vs. 24%, P < .001, and 9 vs. 0%, respectively). Non-steroid users were more likely to have elevated levels of t-PA Ag and PAI-1 than our steroid using weight lifters (both P < .001). The activities of antithrombin III and protein S were more likely to be higher in users compared to nonusers (22 vs. 6%, P = .005; 19 vs. 0%, respectively). Some anabolic-androgenic steroid using weight lifters have an accelerated activation of their hemostatic system as evidence by increased generation of both thrombin and plasmin. These changes could reflect a thrombotic diatheses that may contribute to vascular occlusion reported in young athletes using these drugs. The predictive value of these coagulation abnormalities in terms of risk of thrombosis to individual steroid using weight lifters or the population as a whole remains to be studied.
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PMID:Anabolic-androgenic steroid abuse in weight lifters: evidence for activation of the hemostatic system. 763 72

In septic patients capable of normal white cell responses, high plasma levels of PAI-I, t-PA antigen and t-PA-PAI-I complex were observed. The ratios of t-PA and PAI-I were such that free PA activity was almost never observed. In patients severely leucopenic prior to becoming septic the changes were significantly less marked, so presence of leucocytes enhances the fibrinolytic inhibition occurring in sepsis. The non-leucopenic septic group showed greater evidence of thrombin generation in that FPA levels were higher but fibrinogen levels were only slightly less and antithrombin levels not different from those in the leucopenic group. A greater tendency to fibrin deposition and the striking fibrinolytic inhibition noted in patients with normal white cell responses may contribute to the development of some of the complications of sepsis in which fibrin deposition participates and may explain their relative rarity in leucopenic patients. When shock supervened, levels of PAI-I were high in both leucopenic and non-leucopenic groups, indicating that a source of PAI-I outwith the leucocytes themselves contributes to the phenomena observed.
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PMID:Influence of white blood cells on the fibrinolytic response to sepsis: studies of septic patients with or without severe leucopenia. 764 91

Junin virus, an arenaviridae, is the etiological agent of Argentine hemorrhagic fever. In addition to thrombocytopenia, patients present several alterations in both the blood coagulation and the fibrinolytic system, but diffuse intravascular coagulation could not be demonstrated. To investigate further the activation status of the two systems, levels of thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2, protein C, total and free protein S, C4bBP, antithrombin III, t-PA, PAI-1 and D-dimer were measured. Fourteen patients with a confirmed diagnosis of Argentine hemorrhagic fever were included in the study, 2 were severe, 3 moderate and 9 mild clinical cases, but hemorrhages were slight throughout. Blood samples were collected for 6 consecutive days on admission and on remission. At admission TAT and F1 + 2 levels were increased in 13/14 patients, reaching 0.33 nM (0.06-0.87) and 2.16 nM (0.96-6.5), respectively. PC was low in 4 cases, fPS in 6 and tPS in 2, whereas C4bBP and ATIII values were within normal range. t-PA and D-dimer levels were high in 11/14 patients, reaching 20 ng/ml (2.7-106) and 1660 ng/ml (877-3780) respectively, while PAI-1 was considerably increased in the 2 severe cases and normal in the remainder. These results suggest low level though persistent process of blood coagulation and fibrinolysis activation in this viral hemorrhagic disease. We believe these abnormalities may lead to the well described bleeding manifestations in these patients.
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PMID:Early markers of blood coagulation and fibrinolysis activation in Argentine hemorrhagic fever. 766 17

The thrombogenic risk of contrast agents in coronary angiography is still a topical issue, particularly in comparisons between ionic and nonionic contrast agents. As a complement to a preliminary study, the repercussions on sensitive markers of haemostasis were investigated in vivo in 38 patients undergoing a standard cardiac catheterisation. After randomization, an ionic low osmolality contrast agent (Ioxaglate 320) was used in 19 patients and a nonionic low osmolality contrast agent (Iopromide 370) was used in another 19 patients, according to an identical protocol. The following parameters were assayed in arterial blood samples obtained before and after the examination in each patient: platelet markers: beta-thromboglobulin (beta TG) and platelet factor IV (PF4); prethrombotic markers: thrombin-antithrombin 3 complex (TAT) and prothrombin fragments 1 and 2 (F1 + 2) as well as partial exploration of fibrinolysis: tissue plasminogen activator inhibitors (PAI). Comparison of the results demonstrated platelet activation and the presence of prethrombotic markers in both groups. No significant difference was detected between the two groups of patients. Consequently, there does not appear to be any difference in activation of coagulation between modern, low osmolality, ionic or nonionic contrast agents. This may suggest an equivalent thrombogenic risk.
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PMID:[Comparative thrombotic risk of two contrast agents in coronary angiography]. 770 36

Current prevention or treatment of coronary thrombosis relies on antiplatelet agents (aspirin), antithrombin agents (heparin), and plasminogen activators (t-PA). The purpose of this review is to describe novel antithrombotic agents in each of these classes and to discuss recent and future clinical trials with the new agents. Whereas aspirin is a cyclo-oxygenase inhibitor, the most promising new antiplatelets are directed at an integrin cell surface receptor--glycoprotein (GP) IIb/IIIa--which represents the final common pathway for platelet aggregation. The monoclonal F(ab) antibody c7E3, a chimeric murine-human immunoglobulin G (IgG) fragment, is the most intensively studied to date. c7E3 was assessed by the Evaluation of Platelet Monoclonal Antibody to Prevent Ischemic Complications (EPIC) trial in which 2,099 high-risk angioplasty patients were randomized to bolus (placebo) plus infusion (placebo), bolus (c7E3, 0.25 mg/kg) plus infusion (placebo), and bolus (c7E3, 0.25 mg/kg) plus infusion (c7E3, 10 micrograms/min; 12 hours). The overall event rate at 30 days was significantly decreased from 12.8% (placebo) to 8.3% (c7E3), a 36% relative reduction (p = 0.009). Integrelin is a cyclic heptapeptide with marked specificity for GP IIb/IIIa integrin. It was studied during the Integrelin to Manage Platelet Aggregation to Prevent Coronary Thrombosis (IMPACT) trial, which enrolled 150 routine coronary intervention patients. At endpoint, overall event rate was reduced from 11.9% (placebo) to 5.6% (integrelin). The much larger (4,010 patients) IMPACT-II trial has just completed enrollment to confirm and extend these encouraging results. Hirudin is the prototype of the direct antithrombins; it binds to the active catalytic site and the substrate recognition site (exosite) of thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel antithrombotic approaches to coronary artery disease. 786 68

We attempted to determine if a hypercoagulability state exists in patients with polycythemia vera (PV) and essential thrombocythemia (ET). We studied the hematocrit level, platelet count, use of any antiaggregant drugs, thrombotic or bleeding accidents and plasma levels of antithrombin III, protein C, total protein S, free protein S, vWF:Ag (Von Willebrand's factor related antigen), thrombin-antithrombin complexes, D-dimer, fibrinolytic activity, tissue plasminogen activator, plasminogen and PAI-1 in 33 patients (19 with ET and 14 with PV). PAI-1 plasma concentration was significantly higher in, both ET and PV patients than in the control group, and were higher in those patients with previous thrombotic episodes than in asymptomatic patients or with previous bleeding episodes. Increasing age was associated to more thrombotic episodes while younger patients presented with more hemorrhagic complications. A linear correlation between platelet count and PAI-1 levels in PV patients (r = 0.44, p < 0.05) and ET patients (r = 0.30, p < 0.05) was found. Fibrinolytic activity in patients with ET was significantly decreased when compared to the control group. A hypofibrinolytic state could be an additional factor which could be used as a predictive index of the thrombotic or bleeding tendency in each patient.
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PMID:High plasma levels of plasminogen activator inhibitor 1 (PAI-1) in polycythemia vera and essential thrombocythemia are associated with thrombosis. 799 52


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