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 4 widely available thrombolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA), anisoylated plasminogen streptokinase activator complex (APSAC; anistreplase), streptokinase and urokinase have revolutionised the treatment of acute myocardial infarction and are also effective in treating pulmonary embolism and peripheral arterial thrombosis. Therapeutic efficacy of the agents appears to be similar. Choice of a thrombolytic agent depends more on patient characteristics, availability and familiarity with the drug, cost and differences in tolerability. While overall thrombolytic therapy is relatively safe, these 4 agents differ in their tolerability profiles. Streptokinase has the lowest cerebral haemorrhage rate, anistreplase an intermediate and alteplase the highest rate. The incidence of total stroke is also higher with alteplase and anistreplase than with streptokinase, translating to an actual difference in patient risk of 4 extra strokes per 1000 patients treated. Risk of major bleeding is dependent on predisposing factors and seems to be similar with each agent. The incidence of hypotension with alteplase (4.3% in ISIS-3) is less than with streptokinase or anistreplase (6.8 and 7.2%, respectively in ISIS-3). The incidence of major anaphylactic reactions with streptokinase and anistreplase is low (< 1%). Urokinase and alteplase may be preferred for readministration of thrombolytic therapy and anistreplase is the agent of choice where rapid completion of therapy is desirable. The various agents may have different tolerability profiles with different adjunctive therapies and further data are therefore required.
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PMID:Comparative tolerability profiles of thrombolytic agents. A review. 847 Nov 85

We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels in both PE and DVT patients were significantly increased compared with normal volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were significantly higher than those in DVT patients without PE. These findings indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most sensitive indicators for PE. In these patients, increases in TAT and APC-PCI complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.
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PMID:Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis. 856 33

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

Thrombolytic therapy is used in many cardiovascular diseases other than myocardial infarction and pulmonary embolism. In unstable angina, the results of trials have rather been disappointing. In prosthetic valve thrombosis, the role of thrombolytic therapy is increasing. In peripheral arterial thrombosis, intravenous thrombolysis was practically abandonned and local administration has been tried but no systematic attitude can be deduced. In cerebral arterial thrombosis intravenous alteplase thrombolytic treatment is effective and relatively safe in a well defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan.
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PMID:[Thrombolytic therapy in arterial disorders other than myocardial infarction]. 867 42

Thrombolysis today has become a routine option not only in the treatment of acute myocardial infarction but also in many other manifestations of thromboembolic disease. Until one decade ago, only two plasminogen activators, streptokinase and urokinase, were available for clinical use. They were characterized by limited thrombolytic potencies and major side effects including systemic fibrinogen breakdown, bleeds and stroke. This has prompted the search for new plasminogen activators with better pharmacological and clinical profiles. The first such new plasminogen activators were Anistreplase, a chemically modified version of the streptokinase-plasminogen-activator-complex and tissue-type plasminogen-activator produced by recombinant technology. Both new substances have fueled the development in modern thrombolytic treatment. While the clinical progress with t-PA was confirmed in large, double-blind, randomized, multicenter trials, no real superiority of anistreplase over the traditional plasminogen activators urokinase and streptokinase has been substantiated. While the clinical use of t-PA today has been established for acute myocardial infarction, pulmonary embolism and deep vein thrombosis, current research is focused on further plasminogen activators with further improved thrombolytic properties. This review summarizes the current knowledge on the biochemical and pharmacological properties of the first, second and future generation of plasminogen activators.
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PMID:Thrombolytic agents--an overview. 885 12

Thrombolytic therapy has not been widely used for pulmonary embolism due to less than optimal results with conventional plasminogen activators. We propose a new approach to deliver plasminogen activators to the luminal surface of the pulmonary vasculature to potentially improve dissolution of pulmonary thromboemboli. Our previous studies have documented that a monoclonal antibody (mAb) to angiotensin-converting enzyme (anti-angiotensin-converting enzyme mAb 9B9) accumulates in the lungs of various animal species after systemic administration. We coupled 125I-labeled biotinylated plasminogen activators (single-chain urokinase plasminogen activator, tissue-type plasminogen activator and streptokinase) to biotinylated mAb 9B9, using streptavidin as a cross-linker. The fibrinolytic activity of plasminogen activators was not changed significantly by either biotinylation or by coupling to streptavidin. Antibody-conjugated plasminogen activators bind to the antigen immobilized in plastic wells and provide lysis of fibrin clots formed in these wells. Therefore, antibody-conjugated plasminogen activators bound to their target antigen retain their capacity to activate plasminogen. One hour after i.v. injection of mAb 9B9-conjugated radiolabeled biotinylated single-chain urokinase plasminogen activator, biotinylated tissue-type plasminogen activator or biotinylated-streptokinase in rats, the level of radiolabel was 7.4 +/- 0.8, 5.9 +/- 0.4 and 3.6 +/- 0.4% of injected dose/g (ID/g) of lung tissue vs. 0.5 +/- 0.01, 0.3 +/- 0.01 and 0.6 +/- 0.3% ID/g after injection of the same activators conjugated with control mouse IgG (P < .01 in all cases). Injection of mAb 9B9-conjugated radiolabeled plasminogen activator led to its rapid pulmonary uptake with a peak value 6.2 +/- 1.2% ID/g attained 3 hr after injection. One day later, 2.2 +/- 0.5% of the injected radioactivity was found per gram of lung tissue, although the blood level was 0.13 +/- 0.03% ID/g (lung/blood ratio 16.7 +/- 0.3). Therefore, conjugation of plasminogen activators with anti-angiotensin-converting enzyme mAb 9B9 provides their specific targeting to and prolonged association with the pulmonary vasculature. These results provide a basis for study of the local pulmonary fibrinolysis by mAb 9B9-conjugated plasminogen activators.
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PMID:Targeting of antibody-conjugated plasminogen activators to the pulmonary vasculature. 893 Feb 13

We present the case of a young comatose female patient in whom a massive pulmonary embolism was diagnosed by pulmonary angiography. During the angiography, not only successful thrombolytic therapy with recombinant human tissue-type plasminogen activator (rt-PA) (100 mg) was performed, but measuring of the pulmonary artery pressures, oxygen and carbon dioxide levels was also possible. Thrombolysis seems to be a good alternative to surgical thrombectomy.
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PMID:[Rt-PA thrombolysis in the treatment of massive pulmonary embolism]. 898 7

Adams-DeWeese caval clips have been shown to be effective in preventing pulmonary embolism. However, the use of Teflon clips constitutes a permanent solution for this transient risk. We tested an absorbable caval clip made of currently available synthetic biodegradable polymers in five female beagle dogs. The polymer used was PLA 96 containing 96% L lactic acid and 4% D lactic acid. After placement through a laparotomy, clips were routinely inspected and samples of the material were collected at regular intervals between 3 and 19 months postoperatively. The characteristics of absorption of PLA 96 in the retroperitoneal space were the same as those previously described in the literature. The clip retained its shape, rigidity, and effectiveness for 7 months. Complete degradation of the clip took between 18 and 19 months. Absorption did not cause a major inflammatory reaction and had no thrombogenic effect. Given the small number of animals studied, these results must be considered preliminary.
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PMID:Absorbable Adams-DeWeese caval clip: an experimental study. 898 67

The purpose of this study was to evaluate functional and scintigraphic improvement in patients with pulmonary embolism (PE) according to the kind of treatment and the putative age of the emboli. The study includes 20 patients with both scintigraphic and angiographic diagnosis of PE enrolled in Pisa as a part of two previous multicenter trials: PAIMS 2 and BAPE. All patients were admitted to the Pulmonary Unit of the University of Pisa and treated with recombinant tissue-type plasminogen activator (rt-PA) plus heparin (H) (n = 10) or with H alone (n = 10). Results confirmed previous data, namely that perfusion damage decreases significantly from embolization to 7 days later in both patients treated with rt-PA + H and H alone (p < 0.001), although patients treated with rt-PA + H have a significantly higher perfusion restoration (p < 0.001) and a standard PaO2 increase (p < 0.01). Interestingly, our data also showed that the putative age of the emboli does not influence the efficacy of rt-PA + H treatment, while it does influence that of H treatment alone; in other words, rt-PA + H therapy may act efficaciously not only in fresh, but also in old pulmonary emboli.
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PMID:Resolution of pulmonary embolism: effect of therapy and putative age of emboli. 904 75

The aim of this study was to compare the effects on fibrinogenolysis and thrombin generation of two recombinant tissue-type plasminogen activator (rt-PA) regimens in patients with pulmonary embolism entering a randomised, controlled study with a 1:2 allocation ratio to rt-PA, 100 mg over 2 h (Group A) or rt-PA, 0.6 mg/kg, maximum dose 50 mg, over 15 min (Group B). In both groups the heparin infusion was stopped 2-4 h before starting thrombolytic treatment and resumed accordingly to the activated partial thromboplastin time (aPTT) or thrombin clotting time (TcT). Seventeen patients in Group A and 30 patients in Group B were evaluated before starting thrombolytic treatment and 2, 6 and 24 h after its end for the following parameters: aPTT, TcT, fibrinogen, fibrinogen degradation products (FDP), plasmin-alpha 2 antiplasmin (PAP) and thrombin-antithrombin III (TAT) complexes. The two groups had similar coagulation parameters at baseline. Two h after starting rt-PA, the aPTT was more prolonged in Group A than in Group B patients (P = 0.01). Patients in Group B showed less reduction in plasma fibrinogen levels at all study times after rt-PA treatment (P = 0.008). The increase in plasma FDP (P = 0.037) and PAP (P = 0.001) levels was lower at 2 and 6 h samples in Group B compared with Group A. TcT was prolonged (P = 0.003) and TAT increased (P = 0.001) during treatment without differences between the two groups. AUC0-24 of fibrinogen, FDP and PAP levels confirmed the statistically significant differences (P = 0.04) between the two groups over the entire 24 h period of the study. Three patients in Group A (17.6%) and three (10.0%) in Group B suffered major or other important bleeding. Our results indicate that the administration of weight-adjusted reduced-dose rt-PA bolus produces less impairment of blood coagulation than the FDA approved regimen.
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PMID:Fibrinogenolysis and thrombin generation after reduced dose bolus or conventional rt-PA for pulmonary embolism. The Coagulation Project Investigators of the Bolus Alteplase Pulmonary Embolism Group. 919 18


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