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 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

Previous investigations suggested that heparin administration to humans enhances the tissue type plasminogen activator (tPA) levels in blood, but it remains uncertain whether this effect induces fibrinolysis. We studied the effect of therapeutic levels of heparinization on plasma markers for fibrinolysis in patients suspected of pulmonary embolism (PE). Blood samples were taken from 49 consecutive patients; 28 had confirmed PE, 21 had PE excluded. On admission, the plasma levels of plasmin-alpha 2antiplasmin complexes and D-dimer were significantly higher in the patient group with PE compared to those in whom PE was excluded. After heparinization the tPA levels increased in both groups, showing that this effect was not dependent on the initial level of activity of fibrinolysis. In spite of this increment in tPA levels, the concentrations of plasmin-alpha 2antiplasmin complexes and D-dimer decreased. In conclusion, although heparinization in patients with or without pulmonary embolism does lead to elevated tPA:Ag levels, this is not accompanied by enhanced fibrinolysis.
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PMID:Effects of heparin therapy on fibrinolysis in patients with pulmonary embolism. 924 51

We examined hemostatic abnormalities in 23 patients with acute myocardial infarction (AMI), 10 with pulmonary embolism (PE), and 10 with deep vein thrombosis (DVT). At the onset of AMI, plasma levels of tissue-type plasminogen activator (t-PA), PA inhibitor-I (PAI-I), fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin-plasmin inhibitor complex (PPIC) were significantly increased. Both the plasma total TFPI and free-TFPI levels in the AMI patients were significantly higher than those in the healthy volunteers, PE patients, and DVT patients. There was no significant difference in total TFPI or free-TFPI among patients with PE, those with DVT, and healthy volunteers. One hour after percutaneous transluminal coronary angioplasty (PTCA) in the AMI group, the total TFPI level was further increased, and it was significantly reduced 24 hr after PTCA, to a level similar to that in healthy volunteers. Free-TFPI showed a pattern similar to that of total TFPI. The ratio of free-TFPI/total TFPI was highest 1 hr after PTCA. Increased TFPI in AMI patients might be released from ischemic tissues.
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PMID:Increased tissue factor pathway inhibitor in patients with acute myocardial infarction. 925 77

A case of acute pulmonary embolism and right atrial thrombus "in transit" treated with recombinant tissue plasmin activator is described. An early echocardiographic study in acute pulmonary embolism can detect right atrial thrombus in 15% of the time. It is well known that this finding is associated with poor prognosis, but the best treatment is controversial. The present case, in accordance with other previous reports, suggests the use of systemic fibrinolytic therapy in patients with right atrial thrombus and pulmonary embolism in course.
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PMID:[Fibrinolytic treatment of thrombus of the right atrium causing severe pulmonary embolism]. 952 14

Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were significantly increased in patients with disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT) complex were significantly increased in patients with DIC and in those with TTP. Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC, or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC-PCI complex were significantly increased but not those of APC-alpha(1)-AT complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)-AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those undergoing HD. The receiving operating characteristic (ROC) analysis showed that SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60% with DVT and HD. Since the APC-PCI complex was elevated not only in patients with venous thrombosis but also in those with arterial thrombosis, components of the protein C pathway might be useful markers for the diagnosis of arterial thrombosis.
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PMID:Plasma levels of activated protein C-protein C inhibitor complex in patients with hypercoagulable states. 1093 61

The reciprocal activation of plasminogen and prourokinase (pro-u-PA) is an important mechanism in the initiation and propagation of local fibrinolytic activity. We have found that a bacterial lipopeptide compound, surfactin C (3-20 microM), enhances the activation of pro-u-PA in the presence of plasminogen. This effect accompanied increased conversions of both pro-u-PA and plasminogen to their two-chain forms. Surfactin C also elevated the rate of plasminogen activation by two-chain urokinase (tcu-PA) while not affecting plasmin-catalyzed pro-u-PA activation and amidolytic activities of tcu-PA and plasmin. The intrinsic fluorescence of plasminogen was increased, and molecular elution time of plasminogen in size-exclusion chromatography was shortened in the presence of surfactin C. These results suggested that surfactin C induced a relaxation of plasminogen conformation, thus leading to enhancement of u-PA-catalyzed plasminogen activation, which in turn caused feedback pro-u-PA activation. Surfactin C was active in enhancing [125I]fibrin degradation both by pro-u-PA/plasminogen and tcu-PA/plasminogen systems. In a rat pulmonary embolism model, surfactin C (1 mg/kg, i.v.) elevated 125I plasma clot lysis when injected in combination with pro-u-PA. The present results provide first evidence that pharmacological relaxation of plasminogen conformation leads to enhanced fibrinolysis in vivo.
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PMID:Enhancement of plasminogen activation by surfactin C: augmentation of fibrinolysis in vitro and in vivo. 1200 5

Plasminogen activators (PA) are unique agents that are currently applied as thrombolytic therapy to achieve rapid vascular reperfusion. Regimens of PA plus anticoagulants and antiplatelet drugs have attained a high degree of sophistication and predictable rates of positive clinical outcomes for acute myocardial infarction (MI), ischemic stroke, pulmonary embolism (PE), deep vein thrombosis (DVT), and thrombosed catheters. Included in the repertoire are newly approved mutants of tissue plasminogen activator (TPA), which have biochemical advantages that allow for bolus administration. Yet, despite tremendous effort devoted to enormous trials to establish the clinical efficacy of these agents in acute MI, mortality results are not superior to those with native TPA or streptokinase (SK). Furthermore, all PAs have the potential for hemorrhagic complication, most critically intracranial hemorrhage (ICH), occurring in 0.9% of patients treated with native or mutant TPA. It is possible that a limit of clinical effectiveness has been reached, beyond which more potent PAs do not achieve greater benefit without a serious increase in risk of bleeding. A breakthrough is possible, however, if the risk of ICH could be avoided. One solution is the application of the direct-acting thrombolytic enzyme, plasmin. While intravenous plasmin is not effective when administered systemically, regional infusion to a thrombus induces local thrombolysis. Unlike the PAs, plasmin treatment should not cause hemorrhage from vascular trauma sites, as it is neutralized by antiplasmin in the blood. Animal studies are fully consistent with this approach, which offers potential for achieving a truly regional thrombolytic treatment.
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PMID:Towards safer thrombolytic therapy. 1212 83

Thrombolytic agents are in widespread use for the dissolution of arterial and venous pathologic thrombi. Clinical settings where thrombolysis has played an important role include the acute coronary syndromes, peripheral arterial occlusion, ischemic stroke, deep venous thrombosis, and pulmonary embolism. Thrombolytic agents have been successfully employed in each of these areas, achieving dissolution of the occluding thrombus, reconstitution of blood flow, and improvement in the status of the tissue bed supplied or drained by the involved vascular segment. All clinically available thrombolytic agents act through cleavage of the plasminogen molecule to its active form, plasmin. Despite this similar mechanism of action, the thrombolytic agents differ in several biochemical parameters, including fibrin specificity, fibrin affinity, and relative resistance to inactivating factors in the plasma. Whether these differences account for significant differences in clinical outcome is a matter of some dispute. It is quite possible that in vitro biochemical differences do not have meaningful clinical correlates. However, there exists some evidence to suggest that differences in the risk of distant hemorrhage, idiosyncratic reactions, and the rapidity of clot dissolution do exist. An ideal agent for peripheral vascular thrombolysis would be one that was specific in its actions at the site of pathologic thrombi yet left the important and desirable pathologic thrombi that seal vascular defects unscathed. Although such an agent has not yet been identified, an understanding of the mechanism of action and principles underlying pharmacologic thrombolysis provides the necessary foundation of knowledge to choose a particular thrombolytic agent for a given clinical scenario.
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PMID:Comparison of safety and efficacy of the various thrombolytic agents. 1255 39

The importance of pulmonary embolism (PE) due to venous thrombosis is recognized in the treatment of vascular diseases. We have investigated the physiological effects of plasmin generation in experimental acute PE using mice deficient in plasminogen (Plg-/-) or alpha2-antiplasmin (alpha2-AP-/-). PE was induced by continuous induction of venous thrombus in the left jugular vein by endothelial injury due to photochemical reaction. The mortality of wild-type mice was 68.8% at 2 h after the initiation of venous thrombosis and it was significantly reduced in alpha2-AP-/- mice (41.7%). In contrast, Plg-/- mice did not survive. Histological evidence of thromboembolism in the lung was obtained in all mice. However, whereas a strict thromboembolism was observed in Plg-/- mice, only a few thrombi were detected in the lungs of alpha2-AP-/- mice. Plasma fibrinogen levels measured in mice were not different. When alpha2-AP was infused in alpha2-AP-/- mice, the mortality was indistinguishable from wild-type mice. Tissue-type plasminogen activator (tPA) did not reduce the mortality due to acute PE in wild-type mice. However, in alpha2-AP-/- mice, tPA (0.52 mg x kg-1) significantly decreased the mortality compared with that of alpha2-AP-/- mice without tPA. The bleeding time was not significantly prolonged in either type of mice treated with tPA. The lack of plasminogen increases the mortality due to acute PE while a lack of alpha2-AP decreases the mortality rate, which can be further reduced by tPA administration. Therefore, the combination of inhibition of alpha2-AP with thrombolytic therapy could be beneficial in the treatment of acute PE.
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PMID:Alpha2-antiplasmin plays a significant role in acute pulmonary embolism. 1291 86

The relation of intravascular fibrin to the leucocytic sticking reaction in ear chambers of rabbits injured by heat was investigated in two ways. First, attempts were made to destroy the thin layer of fibrin believed to coat the surfaces of cells involved in the sticking reaction. Second, white cell sticking was studied after fibrinogen had been removed from the blood stream. The results of these experiments were as follows:- 1. Activation of fibrinolysin in vivo by streptokinase did not impair sticking of white blood cells. 2. Administration of streptokinase parenterally did not lower fibrinogen blood levels appreciably even when the amount used was large. 3. Thromboplastin infusions alone reduced circulating fibrinogen to low levels but leucocytic sticking was not prevented. Furthermore, frequent death of animals due to pulmonary embolism made such experiments prohibitive. 4. Addition of streptokinase to thromboplastin infusions protected against embolic deaths but did not influence sticking even though the fibrinogen levels achieved were quite low. 5. Finally, when thrombin was added to infusions of thromboplastin and streptokinase, no circulating fibrinogen could be detected. Under such circumstances leucocytic sticking following heat injury occurred without reduction. These findings were interpreted as evidence against a primary role of the blood clotting mechanism in causing the sticking of white blood cells to injured endothelium. Alternative explanations were discussed.
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PMID:Studies on the pathogenesis of acute inflammation. II. The relationship of fibrinogen and fibrin to the leucocytic sticking reaction in ear chambers of rabbits injured by heat. 1379 25


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