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)

The stress of injury and surgical operation results in an initial increase in the spontaneous fibrinolytic activity of the blood which is followed by a period of reduced activity in the postinjury or postoperative period. This 'fibrinolytic shutdown' is particularly marked in patients with malignant disease and occurs irrespective of whether or not they develop a deep venous thrombosis. It also occurs in patients with benign disease and in these patients is greater, though only on the first postoperative day, in those who develop deep venous thrombosis. Venous occlusion studies suggest that this reduction in spontaneous fibrinolytic activity may be the results of a reduction in the fibrinolytic capacity of the vascular endothelium resulting either from a deficiency of the enzyme plasminogen activator or an inability to release the enzyme from the endothelium. Changes in antiplasmins, the inhibitors of the fibrinolytic system, also occur as a result of the stress of operation. Plasma levels of alpha2-macroglobulin fall while those of alpha1-antitrypsin rise. These changes occur irrespective of the presence of malignant or benign disease and do not appear to influence the development of deep venous thrombosis.
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PMID:Factors affecting the fibrinolytic response to surgery. 8 46

In 23 high risk patients the change in plasminogen activator activity in response to surgical operation was studied by euglobulin lysis time (ELT) and fibrin plate lysis before, during and for up to 6 days following a major surgical procedure. Fibrin degradation products (FDP) were also measured. The aim was to relate any changes to postoperative deep vein thrombosis (DVT) as diagnosed by the 125I fibrinogen test. Peroperative increase and postoperative inhibition of fibrinolytic activity were seen in all the patients. Changes in fibrinolytic activity as measured by the ELT and during the first 24 hours by the fibrin plate technique were similar. This suggests that during this period the response was independent of plasma fibrinogen changes. There was no significant difference in these parameters between patients who developed DVT and those who did not. The relationship between venous thrombo-embolism and elevation of serum FDP was confirmed.
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PMID:Plasma fibrinolysis and postoperative deep vein thrombosis. 96 14

In fifteen patients with a cerebro-vascular accident resulting in an acute hemiplegia there was a subsequent rise in the platelet count and plasma fibrinogen level. There were no significant alterations in platelet adhesiveness, plasminogen activator, plasminogen, FR-antigen and haematocrit. Patients diagnosed as developing deep venous thrombosis with the 125I-fibrinogen technique had a significantly lower platelet adhesiveness and plasminogen level than those who were not.
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PMID:Platelet adhesiveness and fibrinolysis after recent cerebro-vascular accidents and their relationship with subsequent deep venous thrombosis of the legs. 103 1

Altogether 75 patients, 60 of whom had recurrent idiopathic deep venous thrombosis, 10 recurrent superficial thrombophlebitis and 5 retinal venous thrombosis, were given a combination of 100 mg phenformin and 8 mg ethyloestrenol a day for periods varying between 3 and 48 months (mean 16.2). Initially, all the patients had an abnormally low plasminogen activator content in the walls of superficial veins and/or a decreased capacity to release plasminogen activator from the vein walls on venous occlusion of the arms. The combination elicited a significant increase in the spontaneous fibrinolytic activity and in the local fibrinolytic activity during standardized venous occlusion of the arms (assayed on fibrin plates) after treatment for 3 months (p less than 0.001). These activities then remained normal throughout the observation period. In 65 of the 75 patients studied, the plasminogen activator level in the vein wall (histochemically assayed by the method of Pandolfi) was abnormally low intitially. The level had increased significantly after treatment for 3 months (p less than 0.001). After treatment for 12 months all the patients except 2 were normal. The patients in this material had had 2-20 episodes of venous thrombosis, the most recent 5 years before the institution of treatment, in spite of dicoumarol treatment. During treatment 9 thrombotic episodes occurred; in 5 of these patients the fibrinolytic activity of the vessel wall was not normal at the time of the recurrence. Except in 1 patient, who developed lactic acidosis, the side-effects were not severe.
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PMID:Phenformin and ethyloestrenol in recurrent venous thrombosis. 116 15

Thrombolytic therapy is rarely used in venous thromboembolism because of the fear of hemorrhagic complications. Preliminary clinical experiences with recombinant tissue-type plasminogen activator (rt-PA) in patients with deep vein thrombosis have shown that even this fibrin-specific plasminogen activator causes an unacceptable rate of hemorrhagic complications. Theoretical considerations and the available experimental and clinical data suggest that infusion of rt-PA over a short period of time would result in a more favorable risk-benefit ratio. Shortening the period of rt-PA infusion results in higher peak plasma levels, thus allowing a higher concentration of the plasminogen activator on the surface and inside the occluding thrombus. In addition, a bolus infusion can prevent or minimize the interaction between rt-PA and the hemostatic system, reducing the likelihood of a systemic lytic state, of a platelet function defect, and, possibly, of bleeding side effects. In venous thromboembolism animal models, the efficacy of bolus rt-PA can be further increased by the adjunctive administration of an effective antithrombotic treatment. This is because the accretion of new fibrin on the thrombi counteracts the lysis of preformed fibrin and influences negatively the final thrombus size. Effective adjunctive antithrombotic treatment includes either high doses of heparin, producing an unclottable activated partial thromboplastin time (aPTT), or doses of recombinant hirudin, doubling the aPTT. When used as an alternative to rt-PA, bolus doses of a hybrid plasminogen activator with prolonged half-life efficiently reduce thrombus size by lysing preformed and newly formed fibrin. Preliminary clinical experience in patients with pulmonary embolism seems to confirm that rt-PA infused as a bolus is at least as effective as, and probably more effective than, rt-PA infused over a longer period.
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PMID:Bolus thrombolysis in venous thromboembolism. 155 82

This study assessed the efficacy and safety of increasing durations of constant-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) in the treatment of deep vein thrombosis. Patients with venogram-documented proximal lower limb (popliteal, iliofemoral) or upper limb (axillary, subclavian) thrombi were given an initial 2-hour rt-PA infusion at 4 micrograms/kg/min, followed by a maintenance infusion of 1 microgram/kg/min for an additional 4, 22, or 33 hours (mean total rt-PA dosages of 54, 127, and 185 mg). A new quantitative venogram scoring system was applied to the study, based on measurements of thrombus volume before and after completion of treatment. Whereas none of the seven patients given treatment for 6 hours and only one of four given treatment for 24 hours showed significant lysis, four of seven who received a prolonged infusion for 35 hours showed lysis of more than 40% of the original thrombus. Overall, the prolonged 35-hour infusion induced 51% lysis of original thrombus, representing a thrombus volume of 16.7 ml dissolved. Hemorrhagic complications were common in all three groups, with four of 18 patients having significant bleeding, including one massive gastrointestinal hemorrhage, two patients with a decrease in hematocrit of more than 10%, and one patient with an intracranial hemorrhage who recovered completely. Pharmacokinetics of the rt-PA showed a steady state antigen concentration of 240 ng/ml and activity of 200 IU/ml during the initial 2-hour infusion and a postinfusion half-life of 5 minutes. Plasma fibrinogen concentrations decreased to approximately 40% to 50% of initial values with all three treatment regimens, but the nadir fibrinogen concentrations did not correlate with either therapeutic efficacy or bleeding complications. One patient with systemic lupus erythematosus had an unusual allergic reaction that manifested primarily as angioedema. This study suggests that rt-PA infusion of 35 hours induces greater thrombolysis of deep vein thrombosis than does a shorter course of 6 or 24 hours, without an increase in hemorrhagic complications.
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PMID:Comparison of dosage schedules of rt-PA in the treatment of proximal deep vein thrombosis. 158 98

Pancreatic carcinoma is associated with a high frequency of thrombosis. Most patients with thrombotic disease have a defective fibrinolytic defense system caused either by plasminogen activator deficiency, excess of plasminogen activator inhibitor (PAI-1), or a combination of the two. In the current series of 27 patients with pancreatic carcinoma, 17 had had deep vein thrombosis (DVT) since the onset of their malignant disease, and most were found to have high plasma concentrations of PAI-1 antigen and PAI-1 activity. Analysis of singleton samples from each patient yielded no correlation between previous DVT and currently high plasma PAI-1 concentrations. However, serial samples from 14 patients (8 of whom had histories of thrombosis) showed individual values varied sharply with time, with intermittent peaks both in PAI-1 antigen and PAI-1 activity for 11 of the 14 patients. Such variability may contribute to intermittently excessive hypercoagulability because of a relative reduction in fibrinolytic potential. These changes may predispose the patient to have thrombotic events in association with pancreatic carcinoma.
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PMID:Peaks in plasma plasminogen activator inhibitor-1 concentration may explain thrombotic events in cases of pancreatic carcinoma. 159 81

To determine whether the response to thrombolytic therapy for lower-extremity deep venous thrombosis (DVT) can be predicted from the venographic appearance, 139 thrombosed venous segments were analyzed. Initial and follow-up venograms were obtained in 62 patients randomized to 24-hour infusions of recombinant human-tissue-type plasminogen activator (rTPA) (n = 34), rTPA plus heparin (n = 16), or heparin alone (n = 12). Segmental response to therapy was evaluated by means of blinded review of the paired venograms. The response (50%-100% lysis) to rTPA alone was significantly greater in venous segments involved with nonobstructive thrombi than in those with obstructive thrombi (12 of 23 vs five of 51; P less than .005). Results were similar for the combination of rTPA and heparin (five of six vs six of 30, P less than .01). No significant difference was seen in the response of either obstructive or nonobstructive thrombus to heparin alone. Thrombotic tails responded substantially (greater than 50% decrease in size) to rTPA with or without heparin in 22 of 24 patients. The venographic appearance of DVT appears to help in predicting the therapeutic response to thrombolytic therapy.
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PMID:Short-term response to thrombolytic therapy in deep venous thrombosis: predictive value of venographic appearance. 162 Aug 26

An impaired fibrinolytic activity after a venous occlusion test is the most common abnormality associated with thomboembolic disease. To better characterize the causes of abnormal responses we have measured different fibrinolytic parameters, before and after 10 and 20 min of venous occlusion, in 77 patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism and in 38 healthy volunteers. The patients had a lower mean fibrinolytic response to venous occlusion than the controls and higher antigen levels of tissue-type plasminogen activator (t-PA:Ag) and plasminogen activator inhibitor type 1 (PAI-1:Ag). Before venous occlusion, PAI-1 levels were at a molar excess over those of t-PA in all patients and controls. After 20 min of venous occlusion, the release of t-PA from the vascular endothelium resulted in a molar excess of t-PA over PAI-1 in the majority of controls (72%) but only in a minority of patients (39%). To identify patients with fibrinolytic abnormalities, reference intervals (RI) for fibrinolytic activity, t-PA:Ag and PAI-1:Ag were established in healthy controls. None of the patients had low levels of t-PA:Ag, but 17 (22%) had elevated PAI-1:Ag levels before venous occlusion and 12 (16%) exhibited low fibrinolytic activity after 20 min of venous occlusion. Ten of these were among the 17 subjects with high PAI-1:Ag levels before venous occlusion. Thus, the measurement of PAI-1:Ag levels before venous occlusion (i.e. in samples taken without any stimulation) is a sensitive (83%) and specific (89%) assay for the detection of patients with an impaired fibrinolytic response to venous occlusion.
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PMID:Hypofibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism. 163 86

Thirty-two patients with acute, proximal-vein thrombosis were treated with heparin and alteplase (0.25 versus 0.5 mg/kg/24 h during 3-7 days) in a randomized, double-blind, multicenter, European (ETTT) trial. The treatment resulted in a decrease of the venographic Marder's score from 18 (6-25) to 13 (2-24) units (median, range) in Group I (0.25 mg/kg/24 h, n = 15, median decrease 3.0, p = 0.32) and from 17.5 (3-33) to 15.5 (0-27) in Group II (0.5 mg/kg/24 h, n = 16, median decrease 4.0, p = 0.23). Comparison of the sequential venograms could be performed in 14 cases of Group I and in 15 cases in Group II. A minority of patients showed substantial partial recanalization of the initially obstructed veins on the control venogram (one in each treatment group) and most of the control venograms showed either thrombus size reductions (5 in Group I, 7 in Group II) or no change or even deterioration (8 in Group I, 7 in Group II). Major bleedings were observed in 7 patients (7/32, 22%), 5 of them occurring in Group II (5/17, 29%). Thus, the results of the ETTT trial show that the used low dosages of alteplase administered intravenously over 3-7 days in heparinized patients cannot be recommended as a treatment for patients with deep venous thrombosis of lower limbs and/or pelvis. Further studies are needed to define a more suitable dosage regimen of alteplase in this indication.
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PMID:Double-blind, randomized comparison of systemic continuous infusion of 0.25 versus 0.50 mg/kg/24 h of alteplase over 3 to 7 days for treatment of deep venous thrombosis in heparinized patients: results of the European Thrombolysis with rt-PA in Venous Thrombosis (ETTT) trial. 164 20


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