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)

Based on apparent higher recanalization rates of the infarct-related artery, preferential use of thrombolytic agents with high clot specificity has been proposed for treating patients with acute myocardial infarction. In the Thrombolysis in Myocardial infarction (TIMI-I) and European Cooperative Group studies, higher reperfusion rates were observed with alteplase compared with streptokinase, causing many to assume that the former would achieve a greater reduction in early hospital mortality. However, the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI-2) and its associated International Study Group failed to show any differences in 15-day mortality between these agents in more than 20,000 patients. This apparent lack of correlation between reperfusion rates and early mortality may be explained in part when one considers that recanalization or patency rates measured at a given point in time, such as 90 minutes after onset of therapy, fail to define the subsequent vessel status. Early reocclusion is the major reason for this and is a major limitation to the clinical efficacy of thrombolytic drugs. Following recanalization, residual fibrin-bound thrombin adherent to the site of arterial injury from plaque rupture strongly promotes rethrombosis. Although antiplatelet and antithrombin agents such as aspirin and heparin help to decrease rethrombosis, these agents are far from ideal. Thrombolytic agents that produce a significantly prolonged systemic thrombolytic state, such as streptokinase and anistreplase, are likely to result in less rethrombosis. Therefore, a systemic fibrinolytic state would appear to be an advantage rather than a disadvantage, particularly because the incidence of intracerebral hemorrhage does not appear to be greater with their use compared with agents producing less systemic fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolysis, anticoagulation, and reocclusion. 174 47

Prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin complexes (TAT), as well as other coagulation and fibrinolysis parameters, were studied in a series of 13 patients affected by thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS). Fragment F1 + 2 was found to be increased in all patients at diagnosis (patients' range, 1.21-19.03 nmol/l; normal limits, 0.28-1.08 nmol/l), and remained also higher than normal after treatment with plasma exchange (patients' range, 1.5-4.01 nmol/l). Even though the analysis of fibrinolysis markers did not show a definite state of hypo or hyperfibrinolysis in the systemic circulation, enhanced circulating D-dimer levels (0.53-12.6 micrograms/ml, normal levels of 0.03-0.29 micrograms/ml) indicated that a certain grade of fibrin lysis was present at previously formed thrombi. Plasma PAI-1 activities either on admission (9.2-38.2 U/ml) and after plasma exchange therapy (2.6-38.6 U/ml) showed a behavior irrespective of t-PA:Ag changes, and post-plasmapheresis values remained high only in patients with fatal neurological outcome. Nevertheless, no correlations between clinical and laboratory data could be established useful for the TTP/HUS prognosis. We conclude that increased thrombin generation occurring in damaged areas is appropriately inhibited by antithrombin III in the systemic circulation, avoiding consumption coagulopathy to develop in uncomplicated patients. In addition, fibrinolysis data suggest that elevated PAI-1 may decisively favor the development of microvascular thrombi.
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PMID:Thrombin generation and fibrinolysis in the thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. 151 82

Sepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/- 1.5 ng/ml, p less than 0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p less than 0.01). AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/- 26% in severe infectious disease, p less than 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p less than 0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.
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PMID:Fibrinolysis and coagulation in patients with infectious disease and sepsis. 190 55

The levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) and other substances of coagulation-fibrinolysis, such as fibronectin (Fn) and von willebrand factor (vWF) as well as the activity content of antithrombin-III(AT-III) in plasma were determined in 20 patients with acute myocardial infarction (AMI). In 11 of them these measurements were carried out before and after the treatment with urokinase (UK1000 000 IU). The results suggested that the function of coagulation-fibrinolytic system was disturbed in AMI. Thrombolytic treatment with UK could interfere and improve the stabilization of fibrinolytic activity in the body, but these actions last only short time. Some substances of coagulation showed change with UK treatment.
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PMID:[The kinetics of plasma coagulation fibrinolysis levels in acute myocardial infarction before and after treatment with intravenous urokinase]. 190 71

The respective roles of intravascular coagulation (DIC) and fibrinolysis were assessed in severe chronic liver disease by measuring thrombin-antithrombin (TAT) complexes, tissue-type plasminogen activator antigen (tPA Ag) and fibrinogen and fibrin degradation products (FgDP and FbDP respectively) in 66 patients with liver disease caused by cirrhosis (n = 34) or chronic hepatitis (n = 32) as compared to findings in a control group (n = 30). There was a significant increase of TAT complexes (P less than 0.01), tPA Ag (P less than 0.002), FDP and FbDP (P less than 0.001) in patients as compared to controls. FbDP increase was more evident in patients with cirrhosis than in those with hepatitis (P less than 0.01). Significant correlations between these parameters with some liver function tests were also demonstrated. Thus, in patients with severe liver disease, an increased thrombin activity, as demonstrated by high TAT levels; followed by hyperfibrinolysis suggest that a low grade DIC may occur.
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PMID:Thrombin activation and increased fibrinolysis in patients with chronic liver disease. 190 1

Thrombohemorrhagic risk is one of the main limiting factors in extracorporeal circulation. We describe here our experience in managing some life-threatening hematological complications in 58 patients with acute respiratory failure treated with long-term extracorporeal assistance. These patients were studied by clinical and laboratory means to assess questions related to heparin monitoring, coagulation complications and bleeding incidence. We found that two clotting tests, activated partial thromboplastin time (APTT) and activated clotting time (ACT) can be easily used to assess the safety of anticoagulant treatment (therapeutic ranges: APTT from 55 to 95 sec and ACT from 170 to 220 sec). A certain degree of coagulation activation, despite heparin, was indicated by the constant finding of thrombin-antithrombin complexes, while fibrinolytic activation, measured as plasminogen activator activity, was confined to the time of bypass connection and was of no clinical consequence. Platelet function was always impaired without relation to the platelet loss. Disseminated intravascular coagulation (DIC) (13 episodes) and severe bleeding (11 episodes) were major complications. DIC was corrected with a good outcome for 8 of 13 patients, while severe bleeding was correlated with a poor outcome in 8 of the 11 patients, probably because of the severity of the underlying disease.
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PMID:Physiopathology and management of coagulation during long-term extracorporeal respiratory assistance. 211 73

In a series of 447 patients with single vessel angioplasty, 27 (6.0%) had acute thrombotic occlusion early after the procedure. They were treated with combined intracoronary (20 mg)/intravenous (50 mg) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and repeat mild balloon inflations. Reopening of the vessel was achieved in 22 patients (81.5%). Follow-up coronary angiography 24 to 36 h later revealed reocclusion in 12 patients (54.5%). Thrombin levels measured as thrombin-antithrombin-III complex in patients with successful thrombolysis and persistent patency decreased from 8.5 +/- 11.4 micrograms/liter at baseline to 3.5 +/- 1.4 micrograms/liter 120 min after the start of thrombolysis; these levels increased from 9.4 +/- 15.0 micrograms/liter at baseline to 15.7 +/- 13.5 micrograms/liter 120 min after the start of thrombolysis in the patients with unsuccessful thrombolysis or early reocclusion (p less than 0.05). When a borderline value for thrombin-antithrombin-III complex level of 6 micrograms/liter was selected to separate the two groups of patients, patients with an unfavorable clinical course were identified 120 min after the start of thrombolysis by levels greater than 6 micrograms/liter (sensitivity 100%, specificity 92.8%). Thus, after abrupt thrombotic vessel closure during coronary angioplasty, the short-term results of thrombolysis seem to be governed by the release of thrombin. In two thirds of patients, however, the thrombin release cannot be suppressed by concomitant aspirin and heparin therapy. Even after successful reopening of the vessel these patients should therefore undergo immediate aortocoronary bypass grafting.
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PMID:Role of thrombolysis and thrombin in patients with acute coronary occlusion during percutaneous transluminal coronary angioplasty. 211 19

In patients with acute myocardial infarction (AMI) treated with streptokinase (SK) or recombinant tissue-type plasminogen activator (rtPA) we found high levels of thrombin-antithrombin (TAT) complexes signalling a significant activation of the coagulation cascade. In the SK-treated group the median pretreatment TAT complexes levels were 5.0 micrograms/l and in all patients, whatever the pretreatment level, TAT complexes increased following treatment. A statistically significant increase (medians = 20.3 and 12.0 micrograms/l) was observed 90 and 180 min after starting SK. The mean pretreatment level in the rtPA-treated group was also 5.0 micrograms/l and in all but one patients TAT complexes increased following treatment. A statistically significant increase (medians = 37.0 and 30.5 micrograms/l) was observed 90 and 180 min after starting rtPA. There was no statistically significant difference between TAT complexes in the two groups of patients either before or 90 min after treatment, whereas at 180 min the median concentration of TAT complexes was significantly higher for rtPA- than for SK-treated patients. We did not find an association between coronary vessels patency after thrombolysis and concentrations of TAT complexes; however, the rate of occluded vessels was very low (4 out of 30 patients), so that a difference was perhaps lost due to the insufficient size of the sample. In conclusion, we found thrombin activity during thrombolytic therapy in patients with AMI. There is no important difference in this respect between rtPA and SK. Whether or not this phenomenon is responsible for early rethrombosis remains to be explored by larger studies.
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PMID:Elevation of thrombin-antithrombin complexes during thrombolytic therapy in patients with myocardial infarction. 212 14

The concept of the haemostatic balance was reviewed, and its potential role in the regulation of tissue repair and the pathogenesis of thrombotic processes was surveyed. Physiological activation of coagulation appears to be dominated by effects of degenerated and injured cells of the vascular wall causing local release of thromboplastin and exposition of activating surfaces. Inhibition of coagulation impairs its progression and the non-thrombogenic nature of the normal endothelium is chiefly caused by the binding of inhibitory components (antithrombin-III, protein C) to specific receptor sites. Physiological activation of fibrinolysis appears to be triggered by and limited to the fibrin because of a specific affinity to fibrin of plasminogen and plasminogen activators. Systemic activation of fibrinolysis is prevented by primary (alpha 2-antiplasmin) and secondary (alpha 2-macroglobulin, alpha 1-antitrypsin) plasmin inhibitors. A plasminogen binding protein (histidine-rich glycoprotein), plasmin inhibitors and activator inhibitors appear to contribute to the regulation of the initial phase of fibrinolysis. A deviation from normal of the dynamic balance, regulating fibrin formation and resolution, may lead to a haemorrhagic and/or a thrombophilic state. Described were the optimization of selected methods for assessment of variables involved in the haemostatic balance. An overestimation of plasminogen concentrations in plasma may occur in patients with elevated levels of fibrinogen or fibrin degradation products, when using assays based on the activation of plasminogen by streptokinase followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be eliminated by presence of fibrinogen in excess in the plasminogen assay, thereby securing maximum stimulation of the plasminogen-streptokinase complex. The presence of cryoglobulin in plasma interferes with the assessment in euglobulins of plasminogen activator activities. Experiments indicate that tissue-type plasminogen activator adsorb cryoglobulins and that a cold-promoted activation of the factor XII-dependent proactivator system of fibrinolysis is related to the presence of cryoglobulins. Experiments supported the existence of an as yet not characterized factor XII-dependent proactivator. Strictly optimized procedures for the preparation of euglobulins for the accurate determination of plasminogen activators were recommended. The determination of plasminogen activator inhibition in plasma was optimized and simplified. The amidolytic assay of antithrombin-III was shown to be influenced by adsorption to laboratory utensils and aggregation of thrombin. This error could be corrected by protection with additives (Tween 80, polyethyleneglycol 6,000), which also improved the solubility of the chromogenic substrates in aqueous media. The role of thrombosis in myocardial infarction was reviewed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The haemostatic balance in groups of thrombosis-prone patients. With particular reference to fibrinolysis in patients with myocardial infarction. 219 35

The average level of kallikrein assayed as acetone-activated plasminogen activator (PGA) in plasma specimens from 10 reactors to clinical dextran or to radiographic contrast media did not differ from the level in 16 controls. This result was obtained in plasminogen-free citrated plasma stabilized with benzamidine. In the absence of benzamidine a significant reduction of PGA activity was registered in the reactor plasma, but not of activity against the tripeptide substrate S-2302 or the ester substrate BAEe. After storage of the plasma specimens for 12 to 18 months at -70 degrees, the PGA activity obtainable in reactor plasma had increased to the level registered in control plasma. Known inhibitors of plasma kallikrein and of histidine-rich glycoprotein (HRG) were assayed by radial immunodiffusion. The levels of alpha 2-macroglobulin, antithrombin-III and HRG were within the normal range in plasma from reactors, the level of C1-esterase inhibitor was slightly increased (116%), and the level of alpha 1-antitrypsin was higher than normal (124%). Evidence is provided that the loss of PGA activity taking place during acetone activation of fresh reactor plasma could not be due to a transition of native alpha-kallikrein to 3-chain beta-kallikrein. It is concluded that a plasma constituent unstable during storage is responsible for the selective and partial loss of PGA activity registered in reactor plasma.
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PMID:Assay of kallikrein inhibitors and levels of acetone-activated kallikrein in plasma specimens from reactors to dextran or to contrast media. 243 Sep 9


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