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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombolytic therapy provides clinical benefit in patients with vascular occlusions, depending upon the organ or limb that is threatened. The impact of therapeutic intervention varies from the quiet alteration of the course of deep vein thrombosis, for which non-life threatening post-phlebitic syndrome can be largely avoided, to the sometimes striking reversal of pulmonary hypertension and possible life-saving benefit in massive pulmonary embolism, the immediate alteration of clinical course in acute peripheral arterial occlusion by reducing the need for surgical intervention, cardiopulmonary complication and one year mortality, and finally to the dramatic and life-saving potential when applied in patients with acute myocardial infarction. Since the risk of serious hemorrhage, especially intracranial hemorrhage, is a constant, regardless of the underlying thrombotic problem, thrombolytic therapy will necessarily be applied variably according to the different potential therapeutic benefits. The balance of potential benefit versus the risk of intracranial hemorrhage in the situation of cerebrovascular thrombosis and stroke remains to be clarified by ongoing studies. As to the evidence for superiority of any single thrombolytic agent or regimen, direct comparative studies are still needed for patients with venous thrombosis and arterial occlusion. Available direct comparisons of two or three agents (streptokinase, urokinase, alteplase and anistreplase) in studies of pulmonary embolism and myocardial infarction show a consistent pattern that documents positive clinical benefit for all of the agents, with striking similarity in quantitative aspects despite marked differences in biochemical properties of the agents.
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PMID:Thrombolytic therapy: overview of results in major vascular occlusions. 857 40

The authors report on a 33-year old woman with massive, life-threatening pulmonary embolism at the third trimester of pregnancy. The diagnosis was rapidly accomplished in the Emergency Department by two dimensional-Doppler echocardiography that showed signs of pulmonary hypertension as well as a large, floating thromboembolus in the right atrium. As the hemodynamic deterioration persisted after treatment with iv heparin, the patient received alteplase 50 mg as a bolus over 5 minutes. About 30 minutes later, a further 50 mg infusion of alteplase was given over 60 minutes because clinical conditions were progressively worsening. After an alteplase dose of 75 mg, the woman showed a definite improvement in clinical-hemodynamic status and echocardiography documented a reduction of right ventricular overload and atrial clot disappearance. Two hours later the patient was submitted to cesarean section, because of the onset of uterine contractions, and delivered a vital baby. The occurrence of uterine bleeding was antagonized by the infusion of fresh-frozen plasma and a moderate anemia was subsequently treated with iron preparations. The mother and her baby were discharged on 16th day in fairly good general conditions. The authors emphasize the leading role of early echocardiography in the clinical decision making and the lifesaving potential of full dose thrombolytic therapy without serious adverse effects.
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PMID:[Massive pulmonary embolism during the third trimester of pregnancy: effectiveness of thrombolytic treatment with alteplase]. 924 13

We investigated the effects of human inter-alpha-inhibitor (I alpha I) on hemodynamics, oxygenation, and coagulation parameters in a porcine model of endotoxic shock. Four groups of six animals were studied: (1) control, (2) I alpha I group receiving 30 mg/kg I alpha I over 30 min, (3) LPS group receiving 5 micrograms.kg/min Escherichia coli endotoxin over 30 min, and (4) LPS + I alpha I group receiving 30 min after endotoxin 30 mg/kg/30 min I alpha I. We measured hemodynamic and oxygenation parameters, usual coagulation markers and plasma levels of thrombin-antithrombin complexes, antithrombin III activity, plasminogen activator tissue type, plasminogen activator inhibitor type 1, von Willebrand factor, tumor necrosis factor-alpha, and I alpha I at baseline and at 30, 60, 90, 120, 180, 240, and 300 min. In the I alpha I group, plasma I alpha I levels reached 447 +/- 23 mg/L just after injection and 287 +/- 39 mg/L at 300 min. I alpha I half-life was 7.3 +/- 1.9 h. In the IPS + I alpha I group, I alpha I plasma levels decreased more rapidly, reaching 260 mg/L at 300 min. Compared with the LPS group, administration of I alpha I normalized the mean arterial pressure and cardiac index, improved the LPS-induced pulmonary hypertension, and resulted in the blunted increase in blood lactate and oxygen extraction ratio. A significant decrease in thrombin-antithrombin complexes and plasminogen activator inhibitor type 1 levels were observed. There was no significant difference in plasma tumor necrosis factor-alpha levels. We concluded that in this hypodynamic model of endotoxin shock, I alpha I administration resulted in a marked improvement in the hemodynamic, oxygenation, and coagulation parameters.
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PMID:Effects of inter-alpha-inhibitor in experimental endotoxic shock and disseminated intravascular coagulation. 941 62

In a porcine model of Gram-positive sepsis, 28 juvenile pigs were studied to evaluate the effect of a continuous infusion of live serogroup A streptococci (GAS) on the activation of coagulation and fibrinolysis. Plasma levels of thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) activities were measured using commercially available kits. The continuous infusion of GAS [(3-5) x 10(8) colony-forming units/kg per h] caused early signs of severe septicaemia in the pigs, with pulmonary hypertension, systemic hypotension, reduced cardiac output and liver hypoperfusion, ultimately leading to shock with a high mortality. There was a sequential and ordered activation of the coagulation, fibrinolytic and antifibrinolytic systems. GAS infusion induced a gradual, maximally 2.5-fold increase in plasma TAT levels. Plasma t-PA activity levels peaked at 2 h (nine-fold increase), whereas the peak of PAI-1 activity was delayed (eight-fold increase at 4 h). These findings are similar to changes observed during endotoxin infusion. This procoagulant state favours disseminated intravascular coagulation and microthrombus formation, ultimately threatening tissue viability.
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PMID:Systemic activation of coagulation and fibrynolysis in a porcine model of serogroup A streptococcal shock. 1093 4

Successfully utilized contemporary pulmonary embolism thrombolysis reverses right heart failure rapidly and safely. This therapeutic approach may lower mortality from pulmonary embolism and reduce morbidity from chronic pulmonary hypertension. Unlike myocardial infarction thrombolysis, a 2-week 'time window' is available, during which treatment can be initiated. A high concentration of the thrombolytic agent is administered in a brief infusion lasting several hours. No special laboratory testing is needed. Currently, the only contemporary thrombolytic regimen for pulmonary embolism that is approved by the Food and Drug Administration is tissue plasminogen activator, in a dose of 100 mg/2 h. New thrombolytic agents under development for pulmonary embolism include reteplase, saruplase, and recombinant staphylokinase. Future clinical trials will require multicenter collaboration and will focus on relevant endpoints such as the reduction of mortality and recurrent venous thromboembolism.
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PMID:A contemporary approach to thrombolytic therapy for pulmonary embolism. 1094 88

We compared the effects a novel recombinant tissue-type plasminogen activator (rt-PA) E6010 with the more conventional therapeutic agent alteplase in a new canine model of life-threatening acute pulmonary thromboembolism (APTE). Fifty milliliters of autologous blood was obtained from anesthetized, adult mongrel dogs and mixed with 10,000 units of thrombin. The left pulmonary artery, pulmonary vein, and bronchus were ligated, and previously prepared blood clots were injected via the femoral vein until the mean pulmonary artery pressure (mPA) increased to 2.5-3.0 times over baseline mPA (control). E6010 (0.4 mg/kg) or alteplase (1.33 mg/kg) was administered to other animals following inducement of APTE. In control animals, 60 min after embolization, mPA increased from 13+/-3 mm Hg to 31+/-3 mm Hg (p < 0.0001), cardiac output (CO) decreased from 1.47+/-0.35 l/min to 1.15+/-0.39 l/min (p < 0.0001), and PaO2 decreased from 101+/-31 mm Hg to 65+/-20 mm Hg (p < 0.001). E6010 significantly reduced mPA from 31+/-3 mm Hg to 25+/-4 mm Hg (p < 0.0001) 30 min after administration. In the alteplase group, however, mPA did not significantly change. At 180 min following drug administration, further reduction of mPA was significantly observed in both treatments. CO and PaO2 did not improve after either treatment. The present study indicated that E6010 more rapidly reduced pulmonary hypertension in our APTE model. Because of its rapid action, E6010 might be a promising thrombolytic agent for treatment of APTE.
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PMID:Effects of recombinant tissue-type plasminogen activator on life-threatening acute pulmonary thromboembolism in a canine model: a comparative study of e6010 and alteplase. 1117 35

Successfully utilized contemporary pulmonary embolism thrombolysis reverses right heart failure rapidly and safely. This therapeutic approach may lower mortality from pulmonary embolism and reduce morbidity from chronic pulmonary hypertension. Pulmonary embolism thrombolysis remains a debatable indication because large clinical trials using survival as an endpoint have not been carried out. Instead, thrombolysis trials have been undertaken with surrogate endpoints such as reduction in clot burden, reduction in pulmonary arterial pressure, and improvement in right ventricular function. In an era where hundreds of thousands of myocardial infarction patients have participated in thrombolysis trials that focus on survival as the principal endpoint, the much smaller trials of PE thrombolysis have not been sufficiently definitive to achieve a consensus. Pharmaceutical companies have not considered this area of investigation to be a good return on investment, because PE is a much less common problem than acute coronary syndromes. No government funding agency has targeted PE thrombolysis as a priority for clinical research. Currently, the only contemporary thrombolytic regimen for pulmonary embolism that is approved by the Food and Drug Administration is tissue plasminogen activator, in a dose of 100 mg/2 h. New thrombolytic agents under development for pulmonary embolism include reteplase, saruplase, and recombinant staphylokinase. Future clinical trials will require multicenter collaboration and focus on clinically relevant endpoints such as reduction of mortality and recurrent venous thromboembolism.
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PMID:Thrombolysis in pulmonary embolism: a debatable indication. 1148 35

A 69-year-old male presented with symptoms of fulminant lung embolism and, despite immediate therapy with plasminogen activator, died of acute right heart failure. At autopsy multiple tumor cell emboli were detected in small pulmonary vessels in addition to widespread liver metastases from an urothelial carcinoma. - In a 23-year-old female a malignant gastric ulcer and multiple liver metastases were diagnosed at initial presentation. She too died from pulmonary hypertension due to a series of lung embolisms which occurred despite heparin therapy. At autopsy, many small pulmonary arteries were filled with adenocarcinoma cells; the primary gastric tumor and liver metastases were confirmed. These cases demonstrate that the shedding of tumor cells from hepatic metastases can obstruct the pulmonary vessels and lead to acute cor pulmonale. Tumor cell emboli should be considered in the differential diagnosis of acute pulmonary hypertension, especially in patients with a known tumor. They may, however, also represent the first clinical signs of previously unrecognized malignancy.
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PMID:[Tumor cell embolism to pulmonary arteries]. 1155 62

Altered endothelial anti-thrombotic properties have been observed in primary and secondary pulmonary hypertension. In the Eisenmenger syndrome, correlations of these abnormalities with the clinical status and occurrence of chronic intravascular coagulation (CIC) have not been confirmed. The purpose of this study was to investigate whether the occurrence of CIC, as determined by circulating levels of D-dimer is associated with changes in endothelial markers in Eisenmenger patients; and to identify variables that correlate with the severity of clinical presentation. Twenty-one patients were enrolled (ages, 4-52 years). Plasma levels of D-dimer, tissue plasminogen activator (t-PA), thrombomodulin, and von Willebrand factor antigen (vWF:Ag) were measured with enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to differentiate patients with stable (group 1, N=12) from those with unstable disease (group 2, N=9). Increased t-PA (p<0.0001) and vWF:Ag (p=0.001) and decreased thrombomodulin (p<0.0001) were associated with increased D-dimer levels (p=0.0201) in patients. Group 2 had a higher prevalence of affected women (p=0.0242), lower arterial oxygen saturation, and higher t-PA levels compared with group 1 (p<0.0001, discriminant analysis). t-PA and vWF:Ag correlated positively in group 2 (r=0.71, p=0.0309), but not in group 1 (r=0.25, p=NS). Two patients in group 2 but none in group 1 had episodes of pulmonary arterial thrombosis. Endothelial dysfunction is associated with evidence of CIC and correlates to some extent with the severity of symptoms in these patients.
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PMID:Endothelial dysfunction associated with chronic intravascular coagulation in secondary pulmonary hypertension. 1251 85

Successfully utilized contemporary pulmonary embolism (PE) thrombolysis reverses right heart failure rapidly and safely. This therapeutic approach may lower mortality from PE and reduce morbidity from chronic pulmonary hypertension. PE thrombolysis remains a debatable indication because large clinical trials using survival as an endpoint have not been carried out. Instead, thrombolysis trials have been undertaken with surrogate endpoints such as reduction in clot burden, reduction in pulmonary arterial pressure, and improvement in right ventricular function. Currently, the only contemporary thrombolytic regimen for PE that is approved by the Food and Drug Administration is recombinant tissue plasminogen activator, in a dose of 100 mg/2 h. New thrombolytic agents under development for PE include reteplase, saruplase, and recombinant staphylokinase. Future clinical trials will require multicenter collaboration and focus on clinically relevant endpoints such as reduction of mortality and recurrent venous thromboembolism, under particular consideration of the risk of intracranial hemorrhage that ranges between about 1.7% in clinical trials up to approximately 3.0% in a large registry.
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PMID:Thrombolytic therapy in pulmonary embolism. 1519 5


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