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)

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based) rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.
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PMID:Reteplase: a review of its use in the management of thrombotic occlusive disorders. 1691 28

Tenecteplase, a mutant form of alteplase, possesses pharmacological properties that might favor its use for emergent fibrinolysis of acute pulmonary embolism. Contemporaneous search of the World's literature reveals 14 humans with acute pulmonary embolism treated with tenecteplase. Here, we summarize those cases and report the presentation features, dosing details and outcomes of eight additional patients with acute pulmonary embolism treated with tenecteplase in an academic emergency department. None of our eight patients had a significant hemorrhagic event after tenecteplase, and the outcomes of all eight appear to be acceptable. Taken together, we submit that the present case report and prior case reports are sufficient to comprise a phase I study of the safety and efficacy of tenecteplase to treat acute pulmonary embolism.
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PMID:Tenecteplase to treat pulmonary embolism in the emergency department. 1722 30

Reteplase (Retavase) is a plasminogen activator, mimicking endogenous tissue plasminogen activator (t-PA), a serine protease, converting plasminogen to plasmin and thereby precipitating thrombolysis. It is a third-generation recombinant form of t-PA that operates in the presence of fibrin (i.e. it is fibrin specific). Reteplase can be administered as a bolus dose (nonweight-based), rather than an infusion, which promotes rapid and safe administration. The ease of administration of this reteplase dosage regimen (two 10U bolus doses, each over 2 minutes, 30 minutes apart) is conducive to prehospital initiation of thrombolytic treatment in patients with ST-segment elevation myocardial infarction (STEMI), which reduces the time to treatment, a critical factor in improving long-term survival. In large randomized clinical trials of patients with STEMI, reteplase was superior to alteplase for coronary artery patency (according to TIMI [thrombolysis in myocardial infarction] flow) at 60 and 90 minutes, but there was no significant difference between agents for mortality rate and incidence of intracranial bleeding. The 35-day mortality rates were equivalent for reteplase and streptokinase recipients; there was reduced incidence of some cardiac events with reteplase versus streptokinase, but a greater incidence of hemorrhagic stroke. Reteplase has also shown thrombolytic efficacy (in nonapproved indications) as a catheter-directed intra-arterial or intravenous infusion for peripheral vessel occlusions, as 5-minute bolus doses (in 1U increments) for acute ischemic stroke, as a low-dose solution for occluded catheters or grafts, and as an intravenous double bolus for massive pulmonary embolism. Across studies in these indications, the incidence of bleeding complications associated with reteplase treatment appeared to be similar to that associated with other fibrin-specific thrombolytic agents. With its efficacy, and the ease of administration of the bolus doses potentially minimizing dosage errors when treatment is administered under time pressure, reteplase is a valuable option for pre- or in-hospital thrombolytic treatment in patients with STEMI, and is a useful thrombolytic for the treatment of the other thrombotic occlusive disorders described.
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PMID:Spotlight on reteplase in thrombotic occlusive disorders. 1726 91

The movement of thrombi migrating from the veins of the lower limbs can give rise to pulmonary emboli within 24 hours. This is manifested as massive pulmonary embolism in 30% of cases, with a mortality rate of around 50%. Free-floating thrombi within the right cardiac cavities are rare, and the diagnosis is made mainly by transthoracic and transoesophageal echocardiography. Treatment includes surgery, invasive percutaneous embolectomy, thrombolysis and heparin administration. Here we report the case of an 80-years-old patient with massive pulmonary embolism caused by a free floating thrombus within the right atrium. Tenecteplase was administered with excellent results.
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PMID:Free floating thrombus in the right atrium causing massive pulmonary embolism. 1867 23

There are some doubts whether in a severe renal failure the dose of alteplase should not be modified, especially when its plasma clearance may be decreased by liver ischemia. The authors present a case of a 67-year old woman with massive pulmonary embolism (PE) and acute renal failure (creatinine 580 micromol/l) of a mixed etiology (renal calculosis with hydronephrosis and shock as PE presentation). Alteplase administration (10 mg bolus followed by reduced to 50 mg two hours infusion) resulted in hemodynamic stabilization but was complicated by gross subcutaneous hematomas, intensive epistaxis and hematuria, and hemoglobin decrease which required blood transfusions.
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PMID:[Massive pulmonary embolism treated with a reduced dose of alteplase in a patient with acute renal failure]. 1880 42

A 59 year old man underwent mechanical tricuspid valve replacement and removal of pacemaker generator along with 4 pacemaker leads for pacemaker endocarditis and superior vena cava obstruction after an earlier percutaneous extraction had to be abandoned, 13 years ago, due to cardiac arrest, accompanied by silent, unsuspected right atrial perforation and exteriorisation of lead. Postoperative course was complicated by tricuspid valve thrombosis and secondary pulmonary embolism requiring TPA thrombolysis which was instantly successful. A review of literature of pacemaker endocarditis and tricuspid thrombosis along with the relevant management strategies is presented. We believe this case report is unusual on account of non operative management of right atrial lead perforation following an unsuccessful attempt at percutaneous removal of right sided infected pacemaker leads and the incidental discovery of the perforated lead 13 years later at sternotomy, presentation of pacemaker endocarditis with a massive load of vegetations along the entire pacemaker lead tract in superior vena cava, right atrial endocardium, tricuspid valve and right ventricular endocardium, leading to a functional and structural SVC obstruction, requirement of an unusually large dose of warfarin postoperatively occasioned, in all probability, by antibiotic drug interactions, presentation of tricuspid prosthetic valve thrombosis uniquely as vasovagal syncope and isolated hypoxia and near instantaneous resolution of tricuspid prosthetic valve thrombosis with Alteplase thrombolysis.
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PMID:Successful management of multiple permanent pacemaker complications--infection, 13 year old silent lead perforation and exteriorisation following failed percutaneous extraction, superior vena cava obstruction, tricuspid valve endocarditis, pulmonary embolism and prosthetic tricuspid valve thrombosis. 1923 1

Alteplase is standard therapy for patients with acute, massive pulmonary embolism. The novel plasminogen activator desmoteplase displays high fibrin specificity and selectivity for fibrinbound plasminogen. In a preclinical model desmoteplase was twice as potent with a shorter lysis time and lower reocclusion rate. We conducted a phase II study comparing 125, 180, and 250 microg/kg bodyweight desmoteplase with 100 mg alteplase. Efficacy criteria were total pulmonary resistance (TPR), mean pulmonary artery pressure (mPAP), and Miller Index. Intention to treat analysis of 34 patients. The reduction of TPR after 24 hours was comparable between desmoteplase 180 microg/kg and alteplase (-48.0 +/- 22.4 vs. -50.4 +/- 16.3%; p = n.s. vs. alteplase; p = 0.0002 and p<0.0001 vs. baseline). The greatest effect was achieved with desmoteplase 250 microg/kg (-56.0 +/- 29.4%; p = n.s. vs. alteplase, p = 0.0055 vs. baseline). Two hours after treatment PAP was reduced by 27.9 (p = 0.0004 vs. baseline) and 30.4% (p = 0.015 vs. baseline) with the higher doses of desmoteplase and 29.6% with alteplase (p = 0.0006 vs. baseline). Further PAP reduction after 6 hours was most pronounced in the desmoteplase 250 microg/kg group (-40.1 +/- 18.0%; p = 0.0028 vs. baseline). The reduction of the Miller Index was greatest using desmoteplase 250 microg/kg (-35.0 +/- 21.7%; p = 0.011 vs. baseline), and alteplase (-41.6 +/- 27.2%; p = 0.0003 vs. baseline). Safety did not differ among the 4 groups. The study results suggest that desmoteplase at doses of 180 and 250 microg/kg had similar or greater efficacy compared to alteplase 100 mg. Onset of action was faster, safety was comparable.
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PMID:Desmoteplase in acute massive pulmonary thromboembolism. 1927 20

A 35-year-old multiparous woman was found unresponsive, tachypnoeic, hypoxic and in shock 4 h postpartum. The ECG revealed S1 Q3 T3, a right bundle branch block pattern and right-axis deviation. The computed tomography of her pulmonary arteries revealed bilateral pulmonary artery thrombosis with dilated right ventricle. She was fibrinolyzed with intravenous Tenecteplase 30 mg bolus. Her saturation and tachypnoea improved and her ECG reverted to sinus rhythm subsequently. We discuss our use of off-label Tenecteplase in postpartum pulmonary embolism and review the literature.
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PMID:Immediate postpartum cardiorespiratory collapse: a management quandary. 2058 59

Tissue-type plasminogen activator (tPA) remains the sole thrombolytic approved by the FDA for the treatment of pulmonary embolism (PE). tPA has not been replaced by third generation plasminogen activators, e.g. Reteplase (Ret) and Tenecteplase (TNK) that circulate with longer life-spans and in theory should have more extended potency in vivo. One reason for this paradox is the inability to assign units of activity to plasminogen activators based on specific biologically relevant standards, which impairs objective comparison. Here, we compare clot permeation, retention and fibrinolytic activities of tPA, TNK and Ret in vitro and clot composition over time with outcome in a mouse model of disseminated pulmonary microembolism (ME). When clots were incubated in the continuous presence of drug, tPA, TNK and Ret lysed fibrin clots identically in the absence of PA inhibitor-1 (e.g. PAI-1). Ret, which has lower fibrin affinity and greater susceptibility to inhibition by PAI-1 than tPA, was less effective in lysing plasma clots, while TNK was less effective when the fibrin content of the clots was enhanced. However, when clots were afforded only brief exposure to drug, as occurs in vivo, Ret showed more extensive clot permeation, greater retention and lysis than tPA or TNK. These results were reproduced in vivo in a mouse model of ME. These studies indicate the need for more relevant tests of plasminogen activator activity in vitro and in vivo and they show that clot permeation and retention are important potential predictors of clinical utility.
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PMID:Clot penetration and retention by plasminogen activators promote fibrinolysis. 2309 98

A 28-year-old policeman presented with left lower limb deep vein thrombus, pulmonary embolism and a highly mobile right atrial clot. Thrombolytic therapy with IV Tenecteplase was administered. Within a few minutes after the Tenecteplase bolus, the patient's condition worsened dramatically with severe hypotension and hypoxemia. Immediate bedside transthoracic echocardiogram revealed that the mobile right atrium clot had disappeared completely presumably having migrated to the pulmonary circulation thus worsening the clinical condition. With intensive supportive measures the patient's condition was stabilized and he made a complete recovery. Prior to discharge, the echocardiogram revealed normal right ventricular function and a CT pulmonary angiogram performed after 2 months revealed near complete resolution of pulmonary thrombi. Thrombolytic therapy for right heart thrombus with pulmonary embolism can be a reasonable first line therapy but may be associated with hemodynamic worsening due to clot migration.
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PMID:Free floating right atrial thrombus with massive pulmonary embolism:near catastrophic course following thrombolytic therapy. 2399 11


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