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)

In this study the concentration of plasma breakdown products of cross-linked fibrin (XDP), serum fibrinogen-fibrin degradation products (FDP), and plasma fibrinogen were measured before and at the end of the administration of single-chain recombinant tissue-type plasminogen activator (rt-PA, 100 mg IV over three hours) or streptokinase (1.5 million units over one hour), respectively, in two groups, each composed of 22 patients with acute myocardial infarction. The XDP concentration was not statistically different between the two groups at the end of thrombolytic treatment, whereas FDP and fibrinogen concentrations were significantly different (FDP: streptokinase 396 +/- 287 vs rt-PA 177 +/- 222 micrograms/mL, p less than 0.01; fibrinogen: streptokinase 71 +/- 43 vs rt-PA 181 +/- 49 mg/dL, p less than 0.001). These results indicate that the two drugs have equipotent thrombolytic activity at this administration regimen but that rt-PA causes a markedly more selective lysis of fibrin in comparison with streptokinase.
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PMID:Thrombolytic versus fibrinogenolytic activity of rt-PA and streptokinase in patients with acute myocardial infarction. 211 62

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) were measured together with cross-linked fibrin derivatives (XDP), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI-1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 +/- SD 4.0 micrograms/L), PAP (0.7 +/- 0.7 mg/L), and XDP (374 +/- 518 micrograms/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 +/- 0.3 micrograms/L, PAP of 0.2 +/- 0.1 mg/L, and XDP of 30 +/- 14 micrograms/L; P less than 0.005). Plasma concentrations of t-PA and PAI-1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t-PA/PAI-1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.
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PMID:Thrombin and plasmin generation in patients with liver disease. 252 2

In order to define some of the determinants of successful thrombolysis and reocclusion during fibrinolytic therapy for acute myocardial infarction (AMI), specific molecular markers of fibrin metabolism were serially measured in 15 patients with AMI treated with tissue-type plasminogen activator (t-PA). Fibrin formation was assessed by measurement of fibrinopeptide A (FpA) and fibrinolysis by assay of B-beta peptides 1-42 and 15-42 and crosslinked fibrin degradation products (XDP). At baseline, FpA levels were high while markers of fibrinolysis were near normal. Following a 90-minute infusion of t-PA (0.5-1.1 mg kg-1 hr-1), all markers of fibrinolysis increased. Levels of FpA remained elevated despite heparin at the initiation of cardiac catheterization. None of these markers discriminated between patients with successful reperfusion from those without. At 4 hours, B-beta 15-42 peptide and XDP levels remained elevated suggesting persistence of fibrinolysis beyond the short circulatory half-life of t-PA. FpA levels at 4 hours were lower in patients who underwent acute coronary angioplasty compared to those who received additional low dose t-PA (12.3 +/- 4.5 vs. 30.4 +/- 5.5 ng/ml, p less than 0.05). By 48 hours, markers of fibrinolysis had returned toward normal except in 2 patients with persistently elevated B-beta 15-42 peptide levels who suffered reocclusion on days 5 and 6 (75 and 44 vs. 29 +/- 3 nM, p less than 0.005). In conclusion, molecular markers of fibrin metabolism during fibrinolytic therapy may provide clinically relevant data.
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PMID:Fibrin metabolism in patients with acute myocardial infarction during and after treatment with tissue-type plasminogen activator. 297 94

Blood samples from 24 patients who received recombinant human tissue-type plasminogen activator (rt-PA) for angiographically documented acute pulmonary embolism were examined to identify and quantify fibrinolysis. Before and after the intravenous administration of 50 mg rt-PA over a 2 hr period, levels of total fibrinogen, fibrin(ogen) degradation products (FDP), and cross-linked fibrin degradation products (XDP) were measured in each patient. Elevated levels of XDP were found in all patients before treatment (mean 2.0 micrograms/ml, normal less than 0.2 microgram/ml), and these increased 12-fold with treatment. Fibrinogen levels fell 30% and FDP levels increased 24-fold for the entire group of patients. Over this 2 hr period, 10 of 24 patients (responders) demonstrated 25% or greater improvement in the extent of pulmonary artery thrombus as quantified by Urokinase Pulmonary Embolism Trial score, and these patients were found to have a significantly lower XDP/FDP ratio after rt-PA (p less than .04) than those patients who failed to respond. These data suggest that the intravenous administration of pharmacologic doses of rt-PA in patients with pulmonary embolism produces both fibrinolysis and fibrinogenolysis, successful thrombolysis in these patients is associated with a preponderance of fibrinogenolysis over fibrinolysis, the XDP/FDP ratio is a useful indicator of fibrinolytic specificity, and in patients with acute pulmonary embolism the endogenous fibrinolytic pathways are activated, albeit ineffectively, as indicated by the increased circulating XDP levels seen in all 24 patients before the administration of rt-PA.
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PMID:Recombinant tissue plasminogen activator in patients with pulmonary embolism: correlation of fibrinolytic specificity and efficacy. 310 14

Several observations have suggested that lipoprotein (a) (Lp(a)) is a risk factor for coronary artery disease because of potential interference with fibrinolysis secondary to its activation of plasminogen. However, there are few data on the possible role of Lp(a) in liver cirrhosis. The present study was carried out, to better elucidate its relationship to the fibrinolytic system in liver cirrhosis. We studied the plasma levels of Lp(a) and the fibrinolytic parameters of 95 patients with liver cirrhosis (57 men, 38 women, aged 26-81). Patients in Child-Pugh class C (n = 32) had significantly lower levels of Lp(a) than those in class B (n = 45), and the class B had lower Lp(a) values than class A (n = 18) (1.4 (0.0-3.7) vs 2.9 (0.0-6.1) vs 3.4 (1.8-5.5); the data are log-transformed). Alpha-2-antiplasmin and plasminogen, had patterns similar to those of Lp(a), tissue plasminogen activator (t-PA) was significantly increased only in class C (class A: 7.5 +/- 5.8 ng/ml; class B: 10.8 +/- 7.7 ng/ml; class C: 19.1 +/- 11.3 ng/ml). Patients with systemic hyperfibrinolysis (cross-linked fibrin degradation products, XDP > 200 ng/ml) also had lower levels of Lp(a) than those without 1.6 (0.0-4.4) vs (0.0-6.1); p = 0.0002. There was a significant correlation between Lp(a) and plasminogen (r = 0.43; p = 0.001). Lipoprotein (a) progressively decreases as liver cirrhosis worsens but it appears unlikely to be involved in causing the hyperfibrinolytic state often observed in advanced liver cirrhosis, in which there are marked abnormalities of several other fibrinolytic parameters, also including increased t-PA and decreased inhibitors.
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PMID:Lipoprotein (a) and fibrinolytic system in liver cirrhosis. Coagulation Abnormalities in Liver Cirrhosis (CALC) Study Group. 856 64

Recently, a new fibrinogen/fibrin degradation products(FDP) test using monoclonal antibodies against FDP(LPIA FDP-P: FDP-P) has been developed, which is able to measure FDP directly in plasma. The objective of this study is to clarify clinical significance of the test in the diagnosis of fibrinogenolysis and fibrinolysis in comparison with a conventional FDP test using polyclonal antibodies against fibrinogen(FDP-S) and D-dimer test using monoclonal antibodies against D-dimer(D-D). The monoclonal antibodies used in FDP-P test was shown to recognize fragment X, Y and D1 derived from fibrinogen digested by urokinase, and was also to recognize XDP fragments, D-dimer and D derived from cross-linked fibrin digested by tissue plasminogen activator using SDS-PAGE and immunoblotting analysis. There was a good correlation of FDP levels between FDP-P test and FDP-S test. However, levels of FDP in both tests were discrepant in several samples. There was a tendency that the levels of FDP were higher in FDP-S test than in FDP-P test. Such discrepancy was suggesting that soluble fibrin monomer complex(FM) was recognized by the antibodies used in FDP-S test, but not recognized by the antibodies used in FDP-P test. There was also a good correlation of FDP levels between FDP-P test and D-D test. However, the levels of FDP in both tests were discrepant in several samples. The levels of FDP were higher in FDP-P test than in D-D test. These discrepant samples had lower levels of antiplasmin and higher levels of plasmin antiplasmin complex(PIC), and also showed XDP fragments, D-dimer, X, Y, and D1 by using SDS-PAGE. These observations suggest that D-D test measures only fibrinolytic fragments, while FDP-P test measures fibrinogenolytic fragments as well as fibrinolysis. In results, the FDP-P test was confirmed to be a useful tool to examine fibrinogenolysis as well as fibrinolysis more specifically than the conventional FDP test.
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PMID:[Clinical significance of a new fibrinogen/fibrin degradation products(FDP) test using plasma samples for the diagnosis of fibrinogenolysis and fibrinolysis]. 1130 30