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)

Tissue-type plasminogen activator (t-PA), an important component of the fibrinolytic system, is now available as a biotechnologically manufactured recombinant protein for therapeutic use. It has proved highly effective in the clinical therapy of acute thromboembolic diseases such as myocardial infarction and pulmonary embolism. t-PA activates plasminogen to plasmin, which subsequently dissolves the fibrin network of a blood clot. This activation by t-PA occurs selectively on the clot surface, with negligible systemic side effects. The half-life of t-PA in vivo is in the order of minutes due to rapid hepatic elimination. t-PA is a glycoprotein with serine protease activity and consists of a polypeptide chain with 527 amino acids. Recently, intensive research efforts have been devoted to modification of the molecular structure of t-PA, with the objective of further increasing fibrin specificity and catalytic activity, or reducing the rate of elimination. As a result, considerable insights into structure-function relationships within the t-PA molecule have been gained, but as yet no clinically utilizable variant has been constructed which is in all respects superior to naturally occurring t-PA.
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PMID:Properties of molecular variants of tissue-type plasminogen activator. 250 92

A case of massive pulmonary embolism complicated by acute cor pulmonale and shock is presented. The IV administration of recombinant tissue-type plasminogen activator (rt-PA) was associated with prompt reversal of clinical, ECG, and nuclear radiographic findings. The role of thrombolytic therapy with rt-PA for massive pulmonary embolism associated with hemodynamic decompensation deserves further investigation.
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PMID:Rapid resolution of acute cor pulmonale with recombinant tissue plasminogen activator. 250 33

Thrombolytic therapy offers the promise of major therapeutic intervention in many areas as well as in the treatment of patients with acute myocardial infarction who present to the emergency department. Infusion of tissue-type plasminogen activator (tPA) during field transport has been proven safe, but optimal methods for reliably diagnosing acute myocardial infarction in the prehospital setting have yet to be delineated. A major advance would be achieved if thrombolysis were proven effective in preventing the progression of unstable angina to actual infarction. However, early studies have yielded contradictory results. The use of tPA in dissolving peripheral arterial clots appears very promising, but long-term limb survival has yet to be demonstrated. Unlike heparin, thrombolytic agents can also lyse clot in peripheral deep veins and possibly lessen the tendency toward postphlebitic syndrome. The proper dosage regimen to minimize hemorrhage has not been determined. Pulmonary emboli can be lysed by tPA. IV infusion is as effective as intrapulmonary. Significant complications can be minimized, particularly if major vessel catheterization can be avoided for diagnosis. Even after catheterization for pulmonary angiography, however, thrombolytic therapy appears quite promising. The use of thrombolytic agents for embolic-thrombotic stroke is less promising: therefore, the risk of hemorrhagic complication may not outweigh the potential benefit. Thrombolytic therapy thus offers the potential for significant impact on the practice of emergency medicine.
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PMID:Future role of thrombolytic therapy in emergency medicine. 251 90

Clinical experience with thrombolytics in non-coronary disorders is limited to the plasminogen activators streptokinase, urokinase and alteplase; therapeutic trials with anistreplase (APSAC) are almost, and with saruplase completely, limited to acute myocardial infarction. In terms of thrombus clearance, thrombolytic drugs are superior to heparin in patients with recent deep vein thrombosis in the pelvis or lower limbs. In aggregate, thrombi younger than 8 days are lysed in approximately 60% of patients treated with streptokinase, urokinase or alteplase. The results of studies assessing the subsequent development of the postphlebitic syndrome are conflicting, but most suggest that thrombolytic therapy can reduce symptoms of chronic venous insufficiency. Currently, the combination of systemic thrombolytic drugs followed by heparin is recommended for patients with acute major pulmonary embolism who are haemodynamically unstable. Streptokinase, urokinase and alteplase have all been shown to accelerate the lysis of pulmonary emboli and to decrease pulmonary vascular obstruction and pulmonary hypertension. Systemic venous or intrapulmonary infusions of alteplase offers the same benefit in terms of angiographic and haemodynamic improvement. A short infusion of 100 mg alteplase over 2 hours seems to be superior to a 24-hour infusion of urokinase. None of the thrombolytic trials in pulmonary embolism have been large enough to demonstrate a reduction in mortality. It is now generally accepted that, unless contraindicated, thrombolytic therapy is the front-line treatment for patients with massive pulmonary embolism and major haemodynamic disturbance. The local treatment of acute arterial occlusion in limb arteries results in rapid clearing of the artery in 67% of patients treated with streptokinase; the corresponding success rates for urokinase and alteplase are 81% and 88 to 94%, respectively. The main question appears to be the identification of patients in whom local thrombolysis is the treatment of choice, as opposed to established therapeutic modalities. Thrombolytic treatment following a major ischaemic stroke is hazardous, although clinical improvement has been noted in a minority of patients with recanalised cerebral arteries. The safety and efficacy of thrombolytic treatment remains unproven for this indication, and its use must be restricted to experimental protocols. Thrombolytic treatment in retinal artery or vein occlusion has, in practice, been abandoned.
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PMID:Use of thrombolytic drugs in non-coronary disorders. 268 38

Recombinant human tissue-type plasminogen activator (rt-PA) was given via a peripheral vein to 36 patients with angiographically documented pulmonary embolism. The regimen was 50 mg/2 h followed by repeat angiography and, if necessary, an additional 40 mg/4 h. By 6 h, 34 of 36 patients had angiographic evidence of clot lysis, slight in 4, moderate in 6, and marked in 24. The quantitative score improved 21% by 2 h and 49% by 6 h. Fibrinogen decreased 30% from baseline at 2 h and 38% from baseline at 6 h. 2 patients had major complications: in one, bleeding from a pelvic tumour required surgery; in the other, who had had coronary artery bypass surgery eight days earlier, pericardial tamponade developed. These initial results in selected patients make a case for expanded investigational use of peripheral intravenous rt-PA in pulmonary embolism.
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PMID:Acute pulmonary embolism treated with tissue plasminogen activator. 287 27

The effect of intravenous recombinant human tissue-type plasminogen activator (rt-PA) was compared with that of urokinase in 45 patients with angiographically documented pulmonary embolism (PE) in a randomised controlled trial. The two principal end-points were clot lysis at 2 h, as assessed by angiography, and pulmonary reperfusion at 24 h, as assessed by perfusion lung scanning. All patients received the full dose of rt-PA but urokinase infusions were terminated prematurely (on average after 18 h) in 9 patients because of allergy in 1 and uncontrollable bleeding in 8. By 2 h, 82% of rt-PA-treated patients showed clot lysis, compared with 48% of urokinase-treated patients (p = 0.008; 95% CI for the difference = 10-58%). Improvement in lung scan reperfusion at 24 h was identical in the two treatment groups. The reduction in fibrinogen did not differ significantly between the rt-PA and urokinase groups (45% vs 39% at 2 h and 34% vs 40% at 24 h). The results indicate that in the dose regimens employed, rt-PA acts more rapidly and is safer than urokinase in the treatment of acute PE.
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PMID:Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. 289 18

To assess abnormalities of right heart function and their reversal with thrombolysis in pulmonary embolism, serial imaging and Doppler echocardiographic studies were performed before and after a 6 hour intravenous infusion of 80 to 90 mg of recombinant tissue-type plasminogen activator (rt-PA) in seven patients with segmental or lobar acute pulmonary embolism. None of the five men and two women had known prior pulmonary hypertension. Substantial clot lysis and improvement in pulmonary blood flow, as determined by serial pulmonary angiography and perfusion lung scanning, were achieved in all. Coincident with clot lysis, pulmonary artery systolic pressure decreased (from 42 +/- 11 to 26 +/- 7 mm Hg, p less than 0.005), right ventricular diameter decreased (from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm, p less than 0.005) and left ventricular diameter increased (from 3.7 +/- 0.9 to 4.4 +/- 0.6 cm, p less than 0.01). Right ventricular wall movement, initially mildly, moderately or severely hypokinetic in one, two and four patients, respectively, normalized in five and improved to mild hypokinesia in two. Tricuspid regurgitation was present before lytic therapy in six patients. In five, flow velocity in the tricuspid regurgitant jets indicated a peak systolic right ventricular minus right atrial pressure gradient of 25 to 52 mm Hg. Tricuspid regurgitation was detected early after lytic therapy in only two patients. Systolic septal flattening was noted before but not after lysis. These findings confirm that pulmonary emboli may result in appreciable right ventricular dysfunction and dilation, resultant tricuspid regurgitation, abnormal septal position and decreased left ventricular size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early reversal of right ventricular dysfunction in patients with acute pulmonary embolism after treatment with intravenous tissue plasminogen activator. 295 13

The mammalian fibrinolytic system comprises a proenzyme, plasminogen, which can be converted to the active enzyme plasmin, which will degrade fibrin. Plasminogen activation is mediated by plasminogen activators which are classified as either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). t-PA and single-chain u-PA (scu-PA) induce clot-specific thrombolysis, however via entirely different mechanisms. t-PA is relatively inactive in the absence of fibrin, but fibrin strikingly enhances the activation rate of plasminogen by t-PA. This is explained by an increased activity of fibrin-bound t-PA for plasminogen and not by alteration of the catalytic efficiency of the enzyme. scu-PA has a high affinity for plasminogen but, however, does not activate plasminogen in plasma in the absence of a fibrin clot, due to competitive inhibition. Fibrin-specific thrombolysis appears to be due to the fact that fibrin reverses the competitive inhibition, but this does not seem to occur via specific binding of scu-PA to fibrin. The thrombolytic efficacy and fibrin-specificity of natural and recombinant t-PA has been demonstrated in animal models of pulmonary embolism, venous thrombosis and coronary artery thrombosis. In all these studies thrombolysis and relative fibrinogen sparing effect of t-PA was recently confirmed in several multicenter clinical trials in patients with acute myocardial infarction. Specific thrombolysis by scu-PA has also been demonstrated in animal models of pulmonary embolism, venous thrombosis and coronary artery thrombosis.
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PMID:Fibrin-specific thrombolytic agents. 304 5

From the age of 17 a young man had recurrent venous thrombosis, with pulmonary embolism on two occasions. Laboratory investigations showed increased DNA binding, thrombocytopenia, positive antinuclear antibodies, and immunoglobulin A deficiency. A plasminogen activator deficiency was suspected because the euglobulin lysis time was considerably prolonged. Variant lupus was diagnosed. He had a severe myocardial infarct at the age of 20 and subsequent investigations showed the presence in serum of the lupus anticoagulant and antibodies to cardiolipin. The presence of these antiphospholipid antibodies explains the features of his illness and establishes that this case fits into a subset of systemic lupus erythematosus characterised by thrombotic events.
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PMID:Myocardial infarction in a young man with systemic lupus erythematosus, deep vein thrombosis, and antibodies to phospholipid. 308 42

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


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