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)

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

The incidence of deep vein thrombosis (DVT) and pulmonary embolism was studied prospectively in patients undergoing elective total hip replacement. 96 patients were randomly allocated to receive either low molecular weight heparin (LMWH) or unfractionated heparin (UFH). All patients had bilateral phlebography and pulmonary perfusion/ventilation scintigraphy 10-12 days after surgery. The following fibrinolytic variables were analysed in plasma and related to thromboembolism: tissue plasminogen activator (t-PA) activity, t-PA antigen (t-PA Ag), plasminogen activator inhibitor (PAI-1) activity and PAI-1 antigen (PAI-1 Ag). No significant difference was found, regarding the fibrinolytic response to surgery, between patients treated with LMWH and UFH. The level of PAI-1 activity was significantly increased before operation in patients developing DVT as compared to non-DVT patients (p less than 0.03). Immediately after surgery and in the morning the first postoperative day the levels of PAI-1 activity, PAI-1 Ag and t-PA Ag were positively correlated to thromboembolism. PAI-1 activity was the only preoperative fibrinolytic variable correlated to thromboembolism.
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PMID:Impaired fibrinolysis and postoperative thromboembolism in orthopedic patients. 185 6

A 51 year-old man with a history of deep venous thromboses and recurrent pulmonary embolism on long-term anticoagulant treatment was admitted to our department because of insidious onset thrombocytopenia. He had neither a history nor clinical signs of abnormal bleeding. On admission, the platelet count was reduced to 21 x 10(9)/l, platelet associated IgG was increased, and bone marrow specimens showed megakaryocytic hyperplasia. Platelet survival was slightly shortened with enhanced platelet sequestration in a normal size spleen. Laboratory evaluation after discontinuation of anticoagulant treatment revealed persisting prolongation of both the prothrombin time and the activated partial thromboplastin time which could be attributed to the presence of a lupus-type circulating anticoagulant. Further relevant laboratory findings included an elevated titer of IgG anti-cardiolipin antibodies and a reduced euglobulin clot lysis activity after venous occlusion due to increased plasminogen activator inhibitor activity. In recent years, it has become apparent that a striking correlation exists between the presence of antibodies to phospholipids and thromboembolic disease and immune thrombocytopenia respectively. The present case report on the association of these autoantibodies with both, recurrent venous thromboembolism and severe thrombocytopenia, supports the hypothesis that anti-phospholipid antibodies may play a crucial part in the pathogenesis of these clinical conditions. A reduced vascular fibrinolytic capacity may be involved in the thrombophilic state induced by anti-phospholipid antibodies.
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PMID:[Anti-phospholipid antibody with recurrent venous thromboembolism and severe autoimmune thrombocytopenia]. 250 50

Activated protein C (APC)-protein C inhibitor (PCI) complex level was examined in 35 patients with acute pulmonary embolism (PE) and in 20 healthy volunteers. Thrombin-antithrombin III complex, plasmin alpha 2 plasmin inhibitor complex, and fibrin-D-dimer levels were significantly increased in the patients with PE compared to levels in healthy volunteers. Levels of plasminogen activator inhibitor-I, tissue type plasminogen activator, and von Willebrand factor antigens were also significantly increased in patients with PE. Plasma level of APC-PCI complex was increased in most patients with PE and APC-alpha 1 antitrypsin complex level was increased in 13 patients. These complexes were not detected in healthy volunteers. These findings suggested that plasma protein C was activated in patients with PE, and that PCI was the major inhibitor of APC generated in this condition. Thus, regulation of the protein C pathway might play an important role in the pathogenesis of PE.
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PMID:Increased activated protein C-protein C inhibitor complex levels in patients with pulmonary embolism. 751 16

A prospective, randomized, controlled clinical trial was performed comparing the antithrombotic efficacy of the low molecular weight heparin LMWH 21-23, (Braun) with an unfractionated heparin in elective general surgical patients over an observation period of 7 postoperative days. A total of 230 patients were admitted: 103 (group I) received low molecular weight heparin and 100 (group II) low-dose unfractionated heparin treatment given subcutaneously. In group I 41 patients (46%) were operated on for malignant disease and in group II 54 patients (54%). Due to the large amount of great abdominal procedures the intra- and perioperative application of hydroxyethyl starch was allowed for volume substitution. None of the patients died due to fatal pulmonary embolism. In group I four patients revealed positive 125I-labeled fibrinogen uptake (3.9%); two patients belonged to the hydroxyethyl starch subgroup. In group II five patients displayed a positive fibrinogen uptake (5%); two belonged to the hydroxyethyl starch subgroup. The results of the hemostaseological investigations (e.g., prothrombin time, activated partial thromboplastin time, thrombin clotting time, fibrinogen, antithrombin III, protein C, plasminogen, alpha 2-antiplasmin, tissue-type plasminogen activator, plasminogen activator inhibitor) revealed no statistically significant differences between groups I and II or their subgroups, although a tendency to prolonged clotting times was observed. The antifactor Xa activity values, however, displayed a statistically significant difference between the two groups (P < 0.05). The antifactor Xa activity measured up to 0.16 U/ml for the low molecular weight heparin (group I) and 0.05 U/ml for the unfractionated heparin (group II) in the postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prospective randomized clinical study in general surgery comparing a new low molecular weight heparin with unfractionated heparin in the prevention of thrombosis. 789 22

Information is lacking on the mechanisms involved in the organization, resolution, and repair of the vascular lumen after acute pulmonary thromboembolism. Because recent data suggest that the balance between plasminogen activators (PAs) and type 1 plasminogen activator inhibitor (PAI-1) plays a role in regulating cell migration within the extracellular matrix, we investigated the expression of these molecules by immunohistochemical and in situ hybridization analysis of pulmonary artery specimens from patients suffering fatal pulmonary embolism. The data were compared with the expression of these molecules in both patients' noninvolved pulmonary arteries and organ donor pulmonary arteries. Regions of initial organization and vascular remodeling were identified by a modified trichrome stain and by the presence of proliferating cell nuclear antigen (PCNA), a cell marker of proliferation. Staining for tissue-type PA antigen was low to undetectable in endothelial cells directly in contact with the fibrin-platelet thromboembolus and in areas in which the endothelial cell lining was replaced by cell growth into the thrombus. Urokinase-like PA (u-PA) expression was detected in mononuclear cells within the thrombus in the initial phase of thromboembolism and within cells migrating into the thrombus during the later stages of organization. PAI-1 expression was elevated in the monolayer of endothelial cells underlying the fresh platelet-fibrin thromboembolus and in a PCNA-positive cell population present between the pulmonary arterial intima and the thromboembolus that represents early organization. Increased expression of PAI-1 may play a role in inhibiting proteolysis and fostering the localization of the acute fibrin-platelet thrombus to the vascular wall, which is followed by the upregulation of u-PA in migrating cells during the reorganization process.
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PMID:Elevated expression of urokinase-like plasminogen activator and plasminogen activator inhibitor type 1 during the vascular remodeling associated with pulmonary thromboembolism. 959 41

We examined various hemostatic molecular markers in patients with disseminated intravascular coagulation(DIC), deep vein thrombosis(DVT), pulmonary embolism(PE), acute myocardial infarction(AMI), cerebral thrombosis(CT) and thrombotic thrombocytopenic purpura(TTP). Global tests were sensitive for DIC but not for pre-DIC. However, hemostatic molecular markers such as soluble fibrin were sensitive for both DIC and pre-DIC. Hemostatic molecular markers were also useful for analysis of DIC in a baboon DIC model. Activated protein C-protein C inhibitor complex and plasminogen activator inhibitor-I were useful for the diagnosis of DVT, PE, AMI or CT. These findings suggests that hemostatic molecular markers are useful for the diagnosis of various thrombotic disorders.
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PMID:[Application of hemostatic molecular markers for diagnosis of thrombosis]. 1081 Aug 74

The fibrinolytic system plays an important role in the physiological maintenance of blood flow and the dissolution of thrombi. Administration of fibrinolytic agents in indications such as myocardial infarction, pulmonary embolism, deep vein thrombosis or stroke, therefore, offers a rational means to dissolve pathological thrombi and restore vascular patency. The functional domains of the physiological tissue plasminogen activator (t-PA) provide fibrin specificity and serine protease activity for plasminogen cleavage and binding to liver receptors which gives the molecule a short half-life. In order to combat acute thromboembolic events such as myocardial infarction, the structure of the natural t-PA molecule was genetically modified to prolong its half-life, to increase its fibrin-specificity and to improve its resistance to plasminogen activator inhibitor. These features of TNK-t-PA allow bolus administration in emergency situations, early reperfusion of the blood vessel and a low rate of bleeding complications, thus improving the overall benefit to patients.
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PMID:Improving natural principles with genetic engineering: TNK-tissue plasminogen activator. 1145 85

Alteplase (t-PA), a recombinant analogue of human tissue plasminogen activator, became the first genetically engineered thrombolytic approved by the Food and Drug Administration in 1987 for acute myocardial infarction (AMI). In addition to AMI, alteplase is currently approved for the treatment of acute ischemic stroke and pulmonary embolism, and we anticipate approval for catheter clearance in late 2001 in a 2-mg vial configuration. With the withdrawal of human neonatal kidney cell-derived urokinase, alteplase has become an alternative agent in peripheral vascular applications. Because few interventionalists had prior experience with the handling and dosage of alteplase, the Advisory Panel to the Society of Cardiovascular and Interventional Radiology established practice guidelines for use in noncoronary applications. Emerging clinical experience with contemporary dosing regimens shows a safety and efficacy profile similar to urokinase but with significantly reduced drug costs. Tenecteplase (TNK) is a genetically modified version of alteplase. TNK is the only plasminogen activator available that has shown a significantly enhanced safety profile versus alteplase in AMI. Approved for a 5-second, single-bolus injection in AMI, TNK possesses a longer half-life, increased resistance to plasminogen activator inhibitor, and improved fibrin specificity compared with alteplase. Because of its enhanced safety profile, TNK may be a desirable agent for peripheral vascular applications. Initial clinical studies with TNK in acute arterial and venous disease are ongoing. This article outlines the Advisory Panel guidelines for using alteplase and highlights features of tenecteplase.
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PMID:Alteplase and tenecteplase: applications in the peripheral circulation. 1198 95

Acute myocardial infarction is a very rare event during pregnancy and bears the problem of misdiagnosis. However, about 150 cases have been published worldwide with a preponderance of anterior wall infarcts. With more women delaying childbearing until an older age and increasing prevalence of smoking in young women, it can be expected that all forms of coronary artery disease--including acute myocardial infarction--will be seen more often in the future. Among the causes of coronary artery occlusion in pregnancy are (1) rupture of very small coronary artery plaques triggered by different events, e.g., hypertension; (2) plain coronary artery disease; (3) dissection of coronary arteries; (4) coronary artery spasms with/without arterial thrombosis. Prompt diagnosis and immediate therapy are necessary to lower the high mortality of mother and fetus. The gold standard in the therapy of acute myocardial infarction during pregnancy is immediate coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) with or without stent implantation. Application of thrombolytics (recombinant tissue plasminogen activator [rt-PA], r-PA, streptokinase [SK], urokinase [UK]) has been reported in single patients but should be limited to cases where acute PTCA is not available and where the infarct occurs before the 14th week of pregnancy because of possible embryopathy. If the patient is in the last 10 weeks of pregnancy, anticipation of delivery should be part of the medical planning. Consultation with an obstetrician must be obtained as soon as the patient enters the hospital. Besides bleeding complications, venous thrombosis with pulmonary embolism is among the most common causes of death during pregnancy. Pregnancy-related changes in physiology - increase in the resistance to flow from the lower extremities to the heart - and congenital coagulation abnormalities are most important to be recognized. This leads to the fact that superficial and deep venous thromboses occur more often in pregnancy than in the nonpregnant state. Among the coagulation abnormalities found in pregnancy are hypercoagulability (increased levels of fibrinogen, factor VII, factor VIII, factor X), decreased fibrinolytic activity due to an increased level of plasminogen activator inhibitor, increased adhesion and aggregation of platelets, decreased level of protein C and of the APC (activated protein C) ratio. Individual risks factors justifying diagnostic screening include contraception, smoking, immobilization, infection, adiposity, placental insufficiency, and a family history of thrombosis. It is even more important to establish/rule out the diagnosis of thrombosis in pregnancy than in the nonpregnant state, because the use of anticoagulants carries certain risks during pregnancy. Doppler vein studies should be used for diagnosis. If necessary, venography may be used with shielding of the maternal abdomen. Therapy consists of subcutaneous application of heparin, compression, and early mobilization. Alternatively, especially for long-term management, treatment with low molecular weight heparins is feasible. Thrombolytic treatment is contraindicated in most cases due to the high risk of bleeding complications. However, the application of thrombolytics can be contemplated in single cases after careful consideration of the pros and cons. Most cases of pulmonary embolism should also be handled conservatively with heparin. Only in massive pulmonary embolism with severe hemodynamic compromise, thrombolytic treatment is indicated. To guide future therapy in the patients, it is necessary to establish the lifetime risk of recurrent events by determining: APC resistance, prothrombin mutation 20210 A, homocysteine, AT III, protein C and S, antiphospholipid antibodies, and anticardiolipin antibodies.
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PMID:[Myocardial infarction and thromboembolism during pregnancy]. 1275 75


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