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)

Use of urokinase to treat heparin-associated thrombocytopenia and thrombosis in one patient is described, and various treatments proposed for this syndrome are discussed. A 56-year-old man received an intravenous bolus dose of heparin sodium at his local hospital and was transferred to another institution for treatment of suspected pulmonary embolism; he had received heparin two weeks earlier during coronary angiography. The patient's platelet count was reported to be normal before heparin administration. When embolism was confirmed, heparin was discontinued and streptokinase was given for 24 hours. Heparin infusion was then restarted at 1000 units/hr and continued for four days. Platelet count on admission to the second hospital was 47,000/cu mm; 12 hours later it was 19,000/cu mm, and it remained low despite platelet transfusions. Five days after admission, deep-vein thrombosis developed in the left leg. Heparin was discontinued and urokinase and warfarin were started. Urokinase was infused at 320,000 IU/hr for 12 hours and continued at dosages of 160,000-320,000 IU/hr for a total of 40 hours. The initial warfarin sodium dose was 15 mg, followed by a dosage of 10 mg/day. Symptoms of deep-vein thrombosis improved within 12 hours and platelet count increased after heparin was discontinued. If it is recognized early enough, heparin-associated thrombocytopenia can be reversed by discontinuation of heparin. Transfusions of platelets are of little benefit. Dipyridamole, cyclo-oxygenase inhibitors such as aspirin, and protamine sulfate may be useful. Long term anticoagulation with warfarin is recommended to prevent recurrent thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombolytic therapy in heparin-associated thrombocytopenia with thrombosis. 348 69

A case of a 44 year old female with inferior vena cava thrombosis associated with cholelithiasis was reported. The patient had chest and back pain due to pulmonary embolism. Ultrasonic examination showed stone echoes in the gallbladder and thrombus echoes in the inferior vena cava (IVC) at the height from renal veins to bifurcation of iliac veins, but iliofemoral thrombosis was not found by RI angiography and venography. Anticoagulant and urokinase were administered, then pulmonary embolus disappeared and IVC thrombus reduced. IVC thrombus was removed by incision of IVC. Thrombus was white thrombus. Etiology of thrombus was not clear. IVC ligation or plication for prevention of pulmonary emboli was not carried out. Etiology, diagnosis and treatment of IVC thrombosis were also discussed.
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PMID:[A case of inferior vena cava thrombosis associated with cholelithiasis demonstrated by ultrasonic examination]. 352 16

A multicentre trial (10 centres) of urokinase (UK) was performed in patients with acute severe pulmonary embolism (PE). The aim of this trial was, to compare the efficacy of two doses of UK administered via a catheter in the pulmonary artery: 2000 IU kg-1 h-1 for 24 hours (UK 2000) in conjunction with heparin versus 4400 IU kg-1 h-1 UK alone for 12 hours (UK 4400) followed by heparin. PE was less than 5 days old and the clinical diagnosis was confirmed by pulmonary angiograms demonstrating a vascular obstruction of more than 30% (Miller's index greater than 11). The efficacy of treatment was evaluated by the degree of early revascularization (pulmonary angiograms were performed 30 to 48 hours after initiation of thrombolytic treatment and analysed blindly by four independent vascular radiologists). 133 patients were included in this trial: two patients died before treatment and two were excluded retrospectively, leaving 129 patients for final analysis (67: UK 2000 + heparin; 62: UK 4400). The two groups had similar pretreatment clinical, haemodynamic and angiographic characteristics: the Miller angiographic index of severity averaged 22.6 +/- 3.7 for patients in the UK 2000 group, and 22.6 +/- 3.4 for patients in the UK 4400 group (average filling defect of 66% on pulmonary angiograms). There was a similar and significant degree of resolution in the two groups: 26% and 20%, respectively. Minor and major bleeding problems were observed with equal frequency in the two groups (24% and 29%, respectively). These bleeding complications were severe in only 4.5% and 3%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The UKEP study: multicentre clinical trial on two local regimens of urokinase in massive pulmonary embolism. The UKEP Study Research Group. 354 42

The fibrinolytic system comprises a proenzyme, plasminogen, which can be converted to the active enzyme, plasmin, which degrades fibrin. Plasminogen activation is mediated by plasminogen activators, which are classified as either tissue-type plasminogen activators (t-PA) or urokinase-type plasminogen activators (u-PA). Inhibition of the fibrinolytic system may occur at the level of the activators or at the level of generated plasmin. Plasmin has a low substrate specificity, and when circulating freely in the blood it degrades several proteins including fibrinogen, factor V, and factor VIII. Plasma does, however, contain a fast-acting plasmin inhibitor, alpha 2-antiplasmin, which inhibits free plasmin extremely rapidly but which reacts much slower with plasmin bound to fibrin. A "systemic fibrinolytic state" may, however, occur by extensive activation of plasminogen and depletion of alpha 2-antiplasmin. Clot-specific thrombolysis therefore requires plasminogen activation restricted to the vicinity of the fibrin. Two physiological plasminogen activators, t-PA and single-chain u-PA (scu-PA) induce clot-specific thrombolysis, via entirely different mechanisms, however. 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 affinity of fibrin-bound t-PA for plasminogen and not by alteration of the catalytic rate constant of the enzyme. The high affinity of t-PA for plasminogen in the presence of fibrin thus allows efficient activation on the fibrin clot, while no significant plasminogen activation by t-PA occurs in plasma. scu-PA has a high affinity for plasminogen (Km = 0.3 microM) but a low catalytic rate constant (kcat = 0.02 sec-1). However, scu-PA does not activate plasminogen in plasma in the absence of a fibrin clot, owing to the presence of (a) competitive inhibitor(s). Fibrin-specific thrombolysis appears to be due to the fact that fibrin reverses the competitive inhibition. 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 intravenous infusion of t-PA at sufficiently high rates caused efficient thrombolysis in the absence of systemic fibrinolytic activation. The efficacy and relative fibrinogen-sparing effect of t-PA was recently confirmed in three multicenter clinical trials in patients with acute myocardial infarction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Molecular mechanisms of fibrinolysis and their application to fibrin-specific thrombolytic therapy. 355 13

The treatment of a massive or fulminant pulmonary embolism (PE) occurring in the early postoperative phase by embolectomy or fibrinolysis with streptokinase (SK) or urokinase (UK) differs with regard to success and mortality. Embolectomy has a higher mortality and is not practicable in every hospital. Fibrinolysis differs according to substance (SK or UK), dosage, and duration. Five days after extirpation of a leiomyosarcoma--located retroperitoneally in the pelvis--a 72-year-old woman had a massive PE (scintigraphy diagnosis) (Fig. 1). On PEEP-breathing, nitroglycerin (66 micrograms/min), and dobutamin (416 micrograms/min), paO2 and SaO2 showed an increasing tendency, but 4 days after the diagnosis of PE--on the 8th postoperative day--paO2 and SaO2 dropped again (Fig. 3). Fibrinolysis was undertaken with 1.5 million units of SK over a period of 40 min through a Swan-Ganz catheter located in the pulmonary artery. A few hours after the fibrinolytic treatment, paO2 increased at a significant rate and FIO2 could be markedly reduced from 0.7 to 0.4. Twenty-four hours after SK lysis the pulmonary artery pressure (PAP) had still not decreased, but the cardiac output (CO) showed an increasing tendency. The scintigraphic control 17 days after the diagnosis of PE (Fig. 2) correlated with the clinical parameters. The patient was discharged. High-dose ultra-short fibrinolysis with SK in the early postoperative period is discussed in connection with efficiency and bleeding complications ("plasmin-lysis" versus "activator-lysis").
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PMID:[High-dose short time fibrinolytic treatment with streptokinase of massive lung embolism in the early postoperative period]. 363 91

A 27-year-old woman sustained a massive pulmonary embolism (cause unknown) with circulatory arrest. She was intubated and ventilated while external cardiac massage was performed and urokinase was infused (1.5 X 10(6) U/h). These resuscitative measures were continued while she was transferred by helicopter to the nearest cardiothoracic surgical centre, 40 km away. Thrombectomy was successfully accomplished under extracorporeal circulation after (from its onset) 90 minutes of external cardiac massage. No neurological or other sequelae occurred. This case demonstrates that early and continuous resuscitative measures in a general hospital, followed by rapid transfer to a cardiothoracic surgical centre with immediate operation, can achieve a successful outcome.
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PMID:[Successful treatment of a massive pulmonary embolism after 90-minute external heart massage]. 373 66

This study assessed the short-term effects of thrombolytic treatment in 38 patients with massive pulmonary embolism. Thirty-two were treated with streptokinase and six with urokinase. Intrapulmonary artery instillation of fibrinolytic agents was utilized except in 3 patients. There was a marked hemodynamic and arteriographic improvement (p less than 0.0005) in 33 patients (86.8%). Four patients (10.5%) died because of treatment failure. In these cases the fibrinogen concentration remained above 1 gr/liter during therapy. Bleeding was detected in 22 patients (57.8%) but was most often related to puncture or cut-down sites, and only 2 patients (5.2%) had major bleeding. One patient (2.6%) had cerebral hemorrhage. It is concluded that "classic" thrombolytic treatment is to be chosen in life-threatening pulmonary embolism. However, the difficulties sometimes encountered in producing an intense lytic effect and its low fibrinolytic specificity for the thrombus do not permit the obtainment of better results.
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PMID:Massive pulmonary embolism: short-term effects of thrombolytic treatment. 378 63

Heparin is indicated in pulmonary embolism suspicion, in minor and a part of submassive embolism. The dose is 15,000-20,000 U (acute) and 40,000 U/day subsequently. Fibrinolytic therapy with streptokinase or urokinase is indicated in massive embolism. Submassive embolism is treated by fibrinolysis if no contraindications against fibrinolysis are to be registered.
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PMID:[Drug therapy of pulmonary embolism]. 380 72

The pathophysiology of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is briefly discussed, and the efficacy, dosage and administration, laboratory monitoring, and adverse effects of thrombolytic agents, heparin, and warfarin are reviewed. Acute therapy of DVT and PE is usually initiated with intravenous heparin; however, thrombolytic agents such as streptokinase and urokinase may be preferred in patients with massive PE or severe DVT when clot lysis rather than clot stabilization is deemed necessary. For DVT or PE, an intravenous loading dose of streptokinase or urokinase is given, followed by a continuous infusion of the drug. Therapy with streptokinase is continued for 24 hours in patients with PE and for 72 hours in those with DVT; urokinase is continued for 12 hours in patients with PE. Monitoring of blood coagulation tests during thrombolytic therapy is recommended primarily for ensuring that a lytic state is achieved. Intravenous heparin is preferred for acute treatment of DVT or PE; controversy exists regarding whether administration by continuous infusion or intermittent bolus injection is superior. Heparin dosage is usually adjusted to maintain the activated partial-thromboplastin time (APTT) ratio between 1.5 and 2.5; however, the ideal therapeutic range has never been firmly established. After acute treatment with heparin, most patients should continue to receive either warfarin or subcutaneous heparin for several months to prevent recurrent thromboembolism. Bleeding is the major adverse effect of thrombolytic agents and anticoagulants. The risk of bleeding with heparin and warfarin therapy increases with excessive prolongation of the APTT and prothrombin time (PT), respectively. Future clinical trials should further define the role of thrombolytic agents in the treatment of DVT and PE and the efficacy of less-intense warfarin therapy for pulmonary embolism or arterial thromboembolic events.
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PMID:Pathophysiology and treatment of deep-vein thrombosis and pulmonary embolism. 389 Dec

Considerable interest in plasminogen activators as human thrombolytic drugs has stimulated rapid biotechnologic progresses. These enzymes have been classified in two immunochemically distinct groups: "urokinase-like" activators or u-PA which do not interact with fibrin and "tissue activator-like" activators or t-PA which interact with fibrin. Plasminogen activators are widely distributed in normal and malignant tissues and they are implicated in various physiological and pathological processes. They maintain the functional integrity of the vascular system and their presence may be of importance in tissue remodeling and cell migration. Urokinase and streptokinase are used in human thrombolytic therapy. However, the properties displayed by t-PA suggest that this enzyme may be a superior fibrinolytic agent. The primary structures of urokinase and t-PA are known; both enzymes have been synthesized by DNA technology. In order to produce t-PA in large quantities by gene cloning, intensive studies are conducted by pharmaceutical industries. Clinical trials using t-PA for dissolving thrombi in coronary heart disease, strokes and pulmonary embolism are in progress. This review presents the molecular and structural properties of plasminogen activators, as well as related physiological, pathological and therapeutic aspects.
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PMID:[Plasminogen activators: general aspects and recent developments]. 391 65


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