Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The defibrinating agent ancrod has had limited clinical trial, but appears to give no advantages over heparin. Intravenous infusion of dextran, a glucose polymer, has been shown to have an antithrombotic effect in many experimental models of thrombosis. However, the evidence that dextran is a clinically valuable antithrombotic drug is conflicting. A number of controlled randomized studies have shown that dextran can prevent postoperative venous thromboembolism when a large volume of dextran 40 or 70 was infused rapidly during and after surgery. However, blood volume expansion during dextran treatment prohibits its use in patients with reduced cardiac reserve, and infrequent though sometimes severe, allergic reactions have been reported. Evidence that dextran is of value for the treatment of venous or arterial thromboembolism comes from uncontrolled studies and is not convincing. Many compounds have been shown to inhibit platelet function in vitro but only five of these drugs have been extensively evaluated as prophylactic or therapeutic antithrombotic agents in man. These are aspirin, sulphinpyrazone, dipyridamole, hydroxychloroquine and clofibrate. They have been evaluated mainly in patients with cerebral vascular disorders, coronary artery disease, peripheral artery ischaemia, venous thromboembolism, prosthetic heart valves, and in patients with arteriovenous shunts. The evaluation of the clinical effect of the platelet function suppressing drugs is in its early stages, but they appear to differ from each other in the spectrum of their clinical effectiveness, and they may be more effective in arterial than in venous thromboembolic disorders. Their role in the management of cerebral vascular disease and coronary artery disease is still uncertain, and should be clarified by the results of a number of multi-centre, prospective, randomized studies which are currently in progress. Three types of thrombolytic drugs have been evaluated clinically; the plasminogen activators streptokinase and urokinase, proteolytic enzymes such as plasmin, and agents which increase the level of endogenous plasminogen activator (e.g. anabolic steroids). Of these, the plasminogen activators now have a definite place in clinical practice. The plasminogen activators accelerate the lysis of recent venous thrombi and pulmonary emboli, and of arterial thrombi or emboli. Thrombolytic therapy with these agents should be considered particularly in patients with recent major pulmonary embolism, as lysis of recent emboli is rapid and substantial. It should also be considered in patients with recent extensive venous thrombosis, because total lysis of venous thrombi has been reported to result in long-term preservation of valve function, and is likely to prevent postphlebitic syndrome, though this has not been proven. However, plasminogen activator therapy carries a higher risk of bleeding than heparin treatment...
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PMID:Antithrombotic drugs: part II. 78 6

We observed the changes of molecular markers for hemostatic activation in a patient with acute pulmonary embolism treated with 2 x 10(7) unit tissue plasminogen activator (t-PA). Blood samples were obtained before, just after, at 30 min, 1, 2, 6, and 24 hours after the infusion. Molecular markers included thrombin-antithrombin III complex (TAT), plasminogen-alpha 2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). Marked elevation of TAT was observed from immediately after the t-PA infusion to 6 hours after, although it had been observed for only 1 hour in our previous report on the cases of acute myocardial infarction. PIC level was significantly increased during t-PA infusion but returned to almost baseline value 6 hours after the end of t-PA infusion. This finding was almost the same as the one previously reported concerning acute myocardial infarction cases. TM level increased throughout the evaluation, and remained so, even on the 7th day after t-PA infusion. Our present data revealed a clear difference between the reactive TAT increases after t-PA therapy in acute myocardial infarction cases and in acute pulmonary embolism cases. Our present data also revealed a prolonged elevation of TM during the acute period of pulmonary embolism. It is therefore necessary to keep an eye on the changes of molecular markers for hemostatic activation after t-PA therapy in acute pulmonary embolism.
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PMID:[The changes in molecular markers for hemostatic activation after t-PA therapy in case of pulmonary embolism]. 131 73

We describe the successful use of a novel dosage regimen of alteplase in a 77-year-old man with massive acute pulmonary embolism in the presence of a relative contraindication (recent cranial surgery). An intravenous alteplase bolus of 50 mg was administered, followed 40 min later by a 50 mg infusion over 2 h. Pulmonary arteriography showed a considerable increase in intraluminal filling of thrombotically occluded vessels as a result of alteplase administration, and was accompanied by marked clinical improvement. Peak alteplase plasma concentration after the bolus was 5.5 micrograms/ml, and the steady state concentration during infusion was 0.52 micrograms/ml. Detailed monitoring of haemostasis parameters showed elevated endogenous fibrinolytic activity at baseline, very high levels of fibrin degradation products during treatment resulting from lysis of an extensive thrombus mass, moderate fibrinogenolysis compared to fibrinolysis, long plasma half-lives of fibrin(ogen) degradation products (9.2-11.0 h), and increased thrombin generation. There were no bleeding side-effects. The regimen combines the advantages of rapid onset (bolus) and maintained potency (infusion) of thrombolytic effect in pulmonary embolism.
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PMID:Thrombolysis using consecutive high dose bolus and infusion of alteplase in a patient with acute massive pulmonary embolism. 142 Aug 24

Animal studies have demonstrated that thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is accelerated and that bleeding is reduced when rt-PA is infused over a short period. Previous clinical studies in patients with venous thromboembolism have shown that rt-PA is an effective thrombolytic agent when administered by continuous infusion over 2 to 24 hours. Clinical experience of bolus rt-PA administration in patients with massive acute pulmonary embolism (PE) is, however, limited. A prospective open study was conducted in which 54 patients with massive PE (Miller index > or = 20 of 34) received a 10-minute infusion of rt-PA at a dose of 1 mg/kg. Perfusion lung scanning was used to assess the change in pulmonary perfusion after drug administration. At 48 hours and 10 days, the mean absolute improvements in the perfusion defect were 11 and 31%, respectively. In addition, a significant clinical improvement occurred within 2 hours in 11 of the 15 shocked patients. Five patients died (9%) as a result of persistent shock (3 patients), neurologic damage (1 patient) or intracranial bleeding (1 patient). Major bleeding occurred in 8 patients (15%). Long-term follow-up information was available for 44 of the 49 discharged patients: 2 had died and 12 (27%) complained of persistent exertional dyspnea, 7 of whom had an associated heart or lung disease or chronic thromboembolism at admission. These results suggest that a bolus regimen of rt-PA could provide a convenient approach to thrombolytic therapy in patients with massive PE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effectiveness and safety of bolus administration of alteplase in massive pulmonary embolism. 144 21

The clinical diagnosis of venous thromboembolism, and especially pulmonary embolism, is inaccurate due to the nonspecific nature of presenting symptoms and signs which overlap with other frequently coexistent conditions. In recent years, the operating characteristics of more objective diagnostic strategies (ie, ventilation/perfusion lung scan, impedance plethysmography, venous compression ultrasound) have been more clearly defined. However, data regarding the natural history of pulmonary embolism primarily come from an era when objective diagnostic tests were unavailable which calls into question the validity of such data. Furthermore, despite a long experience there are few data regarding the clinical course of pulmonary embolism as currently treated with heparin/warfarin anticoagulation. Acute mortality correlates with the presence of systemic hypotension regardless of embolus size, suggesting that right heart functional reserve is the major determinant of acute survival. Long-term mortality has been attributed to underlying co-morbid disease. However, there are no studies of age- and sex-specific survival which control for co-morbid disease. Pulmonary embolism may be a marker for severe and imminently fatal co-morbid disease, or pulmonary embolism may add "excess mortality" over and above that co-morbid disease. Thrombolytic therapy clears pulmonary artery thrombus more rapidly than heparin and can rapidly restore normal right heart function. Current research aims to identify the ideal plasminogen activator and dosing regimen which maximizes thrombolysis and minimizes disturbance of hemostasis. In addition, more data regarding the natural history and clinical course of pulmonary embolism is needed to stratify patients into subsets with better or worse prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An analysis of current pulmonary embolism therapy. 152 54

rDSPA alpha 1 (recombinant Desmodus salivary plasminogen activator alpha 1) is a recombinant protein corresponding to a natural plasminogen activator from the vampire bat Desmodus rotundus. The thrombolytic properties of rDSPA alpha 1 and tissue-type plasminogen activator (t-PA) were compared in a rat model of pulmonary embolism. Whole blood clots, produced in vitro and labeled with 125I-fibrinogen, were embolized into the lungs of anesthetized rats. Thrombolysis was calculated from the difference between initial clot radioactivity and that remaining in the lungs at 60 minutes. Blood was sampled for gamma counting, measurement of hemostatic factors, and plasminogen activator antigen levels. Thrombolysis at 3, 10, 30, and 100 nmol/kg intravenously (10% bolus, 90% over 60 minutes) amounted to 30% +/- 2%, 51% +/- 4%, 85% +/- 4%, 98% +/- 0% for rDSPA alpha 1 and 30% +/- 3%, 41% +/- 3%, 57% +/- 6%, 93% +/- 2% for t-PA (controls: 29% +/- 2%; mean +/- SEM, n greater than or equal to 6). t-PA at 100 nmol/kg significantly decreased fibrinogen, plasminogen, and alpha 2-antiplasmin levels by 33% +/- 7%, 38% +/- 8%, and 61% +/- 9%, whereas rDSPA alpha 1 at 100 nmol/kg only lowered alpha 2-antiplasmin significantly (by 29% +/- 6%). Compared with t-PA, rDSPA alpha 1 is the more potent and more clot selective (fibrin specific) thrombolytic agent. These results suggest that rDSPA alpha 1 may be safer and more efficacious than currently used thrombolytics.
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PMID:Thrombolytic properties of Desmodus rotundus (vampire bat) salivary plasminogen activator in experimental pulmonary embolism in rats. 153 47

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

Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism.
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PMID:Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial. 160 32

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

We report on successful thrombolytic treatment of massive pulmonary embolism in a patient in early pregnancy with recombinant tissue-type plasminogen activator (rt-PA). Therapy was started with 20 mg rt-PA intravenously over 20 minutes, followed by two further infusions of 20 mg rt-PA within the next 8 hours. Clinical symptoms and haemodynamic parameters improved 24 hours after initiation of therapy. No bleeding complications were observed and the foetus was not affected. Further thromboembolic episodes could be prevented by anticoagulation with low molecular weight heparin up to full term normal delivery.
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PMID:[Thrombolytic therapy of pulmonary artery embolism in early pregnancy with recombinant tissue-type plasminogen activator]. 165 84


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