Abstract:
:The Tissue Factor/Factor VIIa (TF/FVIIa) complex is an attractive target for pharmacological interruption of thrombin generation and hence blood coagulation, as this complex is the initiation point of the extrinsic pathway of coagulation. TF is a cell membrane-associated protein that interacts with soluble FVIIa to activate factors IX and X resulting in a cascade of events that leads to thrombin generation and eventual fibrin deposition. The goal of this non-randomized study was to evaluate XK1, a specific protein inhibitor of TF/FVIIa, and compare antithrombotic efficacy and bleeding propensity to a previously described Factor Xa (FXa) inhibitor (SC-83157/SN429) and a direct-acting thrombin inhibitor (SC-79407/L-374087) in an acute rat model of arterial thrombosis. All saline-treated animals experienced occlusion of the carotid artery due to acute thrombus formation within 20 minutes. Rats treated with XK1 exhibited a dose-dependent inhibition of thrombus formation with full antithrombotic efficacy and no change in bleeding time or total blood loss at a dose of 4.5 mg/kg, i.v. administered over a 60 minute period. FXa inhibition with SC-83157 resulted in complete inhibition of thrombus formation at a dose of 1.2 mg/kg, i.v.; however, this effect was associated with substantial blood loss. Thrombin inhibition with SC-79407 also afforded complete protection from thrombus formation and occlusion at a dose of 2.58 mg/kg, i.v., and like SC-83157, was associated with substantial blood loss. These data imply that TF/FVIIa inhibition confers protection from acute thrombosis without concomitant changes in bleeding, indicating that this target (TF/FVIIa) may provide improved separation of efficacy vs. bleeding side-effects than interruption of coagulation by directly inhibiting either FXa or thrombin.
journal_name
J Thromb Thrombolysisjournal_title
Journal of thrombosis and thrombolysisauthors
Szalony JA,Taite BB,Girard TJ,Nicholson NS,LaChance RMdoi
10.1023/a:1023228827733subject
Has Abstractpub_date
2002-10-01 00:00:00pages
113-21issue
2eissn
0929-5305issn
1573-742Xpii
5120287journal_volume
14pub_type
杂志文章abstract::The duration of oral anticoagulant therapy for venous thromboembolism (VTE) depends on the risk of recurrence if treatment is stopped and the risk of bleeding if treatment is continued. If the risk of recurrence is low (e.g., thrombosis provoked by a major reversible risk factor such as surgery), 3 months of treatment...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,评审
doi:10.1023/a:1012790511790
更新日期:2001-09-01 00:00:00
abstract::Subtilisin QK, a new fibrinolytic enzyme, could cleave directly cross-linked fibrin in vitro. To verify the thrombolytic function of Subtilisin QK in vivo, the thrombolytic effect of purified Subtilisin QK on tail-thrombus of mouse was investigated. After injected with carrageenan, the tail-thrombus of Subtilisin QK t...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-009-0333-3
更新日期:2009-11-01 00:00:00
abstract::The anticoagulant properties of a novel RNA aptamer that binds FIXa depend collectively on the intensity of surface contact activation of human blood plasma, aptamer concentration, and its binding affinity for FIXa. Accordingly, anticoagulation efficiency of plasma containing any particular aptamer concentration is lo...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-012-0778-7
更新日期:2013-01-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,多中心研究
doi:10.1007/s11239-012-0698-6
更新日期:2012-04-01 00:00:00
abstract::Plasminogen activator inhibitor (PAI-1), a member of the serine protein family, is the most active in vivo inhibitor of fibrinolysis induced by plasminogen, tissue plasminogen activator (tPA), and urokinase type plasminogen activator (uPA). While the association between elevated PAI-1 and thrombogenesis has been well ...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,评审
doi:10.1023/a:1008907001042
更新日期:1999-08-01 00:00:00
abstract::Patients with acute leukemia frequently develop catheter-related thrombosis (CRT) despite concurrent thrombocytopenia. The incidence, treatment and outcomes of this complication are poorly documented. We undertook this study to determine the incidence of CRT in patients with acute leukemia and assess the safety and ef...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-018-1711-5
更新日期:2018-10-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-007-0010-3
更新日期:2007-10-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,评审
doi:10.1007/s11239-009-0392-5
更新日期:2010-01-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 临床试验,杂志文章
doi:10.1007/s11239-008-0262-6
更新日期:2009-07-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,评审
doi:10.1007/s11239-006-5574-9
更新日期:2006-02-01 00:00:00
abstract::Kuperman et al. found that patients with anemia had a higher risk of major bleeding (RR 2.84; 95% CI 2.52-3.39) in RIETE database. Anemia appeared to be an independent predictive factor for major bleeding [hazard ratio (HR) 1.95; 95% CI 1.72-2.20] in this registry. Unfortunately, selection bias due to enrolled patient...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 信件,多中心研究
doi:10.1007/s11239-018-1668-4
更新日期:2018-07-01 00:00:00
abstract::A definitive diagnosis of heparin-induced thrombocytopenia (HIT) is difficult to make, especially in patients undergoing cardiac surgery. In this retrospective cohort study, we assessed the platelet count trends and the response to fondaparinux in a population of patients of suspected HIT after pulmonary endarterectom...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-020-02260-y
更新日期:2020-09-07 00:00:00
abstract:BACKGROUND:The role of alpha2-antiplasmin (alpha2-AP) on platelet aggregation was investigated using mice deficient in alpha2-AP (alpha2-AP(-/-)) or using wild type mice (alpha2-AP(+/+)). METHODS:Blood samples were taken from each mouse under anesthesia with ether and platelet rich plasma (PRP) was prepared. Platelet ...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1023/a:1025096609558
更新日期:2002-12-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1023/a:1018738502654
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:Pharmacoinvasive therapy for the treatment of ST elevation myocardial infarction (STEMI) is a strategy that combines early restoration of coronary flow via pharmacologically induced thrombolysis with subsequent, prompt percutaneous coronary intervention (PCI). Prior studies suggesting a heightened bleeding r...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-005-0344-7
更新日期:2004-12-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,评审
doi:10.1007/s11239-011-0594-5
更新日期:2011-10-01 00:00:00
abstract::The benefit of intravenous thrombolysis (IVT) has been questioned for patients with diabetes mellitus (DM) in cases of acute ischemic stroke (IS). Our objective was to analyze the differences in outcome according to prior diagnosis of DM and the use or not of IVT. Observational study with inclusion of consecutive IS p...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-014-1110-5
更新日期:2014-11-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-020-02054-2
更新日期:2020-05-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,多中心研究
doi:10.1007/s11239-009-0316-4
更新日期:2009-11-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-019-01968-w
更新日期:2020-07-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-020-02104-9
更新日期:2020-08-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/BF00181659
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:Radiographic contrast agents inhibit fibrinolysis, although by poorly defined pathways. The purpose of this study was to define specific mechanisms by which contrast agents inhibit clot lysis. METHODS AND RESULTS:Diatrizoate (high osmolar ionic agent), ioxaglate (low osmolar ionic), and ioversol (nonionic) ...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1023/a:1015283210156
更新日期:2001-12-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-020-02237-x
更新日期:2020-07-29 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-020-02191-8
更新日期:2021-01-01 00:00:00
abstract::On stimulation of platelets with agonists, for example, thrombin, a rapid rise in intracellular pH is observed. This alkalinization is mediated by an increase in transport activity of the Na(+)/H(+) exchanger isoform NHE1. In addition to this Na(+)/H(+) exchange mechanism, platelets express bicarbonate/chloride exchan...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,评审
doi:10.1023/a:1008986329267
更新日期:1999-07-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-014-1077-2
更新日期:2014-10-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2019-05-01 00:00:00
abstract::The effect of taurine on the plasma levels of L-arginine, asymmetrical dimethylarginine (ADMA) and L-arginine/ADMA ratio and nitric oxide was investigated in experimental endotoxemia. L-arginine and ADMA levels were quantified by high performance liquid chromatography with fluorescence detector. Nitric oxide level was...
journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章
doi:10.1007/s11239-007-0011-2
更新日期:2007-08-01 00:00:00
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journal_title:Journal of thrombosis and thrombolysis
pub_type: 杂志文章,评审
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更新日期:2016-01-01 00:00:00