Abstract:
:Using an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37 degrees C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, alpha 2-antiplasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p < 0.001) and age (p < 0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-induced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Colucci M,Scopece S,Gelato AV,Dimonte D,Semeraro Nsubject
Has Abstractpub_date
1997-04-01 00:00:00pages
725-9issue
4eissn
0340-6245issn
2567-689Xjournal_volume
77pub_type
临床试验,杂志文章abstract::Enhanced adhesion of sickle erythrocytes to the vascular endothelium and subendothelial matrix is fundamental to the development of vascular occlusion in sickle cell disease. Erythrocyte membrane sulfatide is implicated in the pathogenesis of vasoocclusive crises in sickle cell disease (SCD) patients. Because previous...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-11-0716
更新日期:2011-06-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1655744
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
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更新日期:2006-02-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-05-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-10-29 00:00:00
abstract::Recombinant human activated protein C (APC), which has both anticoagulant and anti-inflammatory properties, improves survival of patients with severe sepsis. This beneficial effect is especially apparent in patients with pneumococcal pneumonia. Earlier treatment with APC in sepsis has been associated with a better the...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH11-06-0438
更新日期:2011-12-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2016-08-01 00:00:00
abstract::Homozygous carriers of factor V Leiden have an approximately 80-fold increased risk of venous thrombosis. Also double heterozygous carriers of both the factor V Leiden and the prothrombin gene mutations are at high thrombotic risk. The magnitude of the risk of venous thrombosis in pregnant women with the two severe th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:
更新日期:2001-09-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究,随机对照试验
doi:
更新日期:2009-03-01 00:00:00
abstract::In high-risk and complicated coronary intervention, the risk of acute closure is unpredictable. Thrombus and platelet deposition at the intervention site may also have further effects on subsequent restenosis. In vivo infusion of activated protein C has previously been shown to achieve potent anticoagulation without a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-03-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-01-0080
更新日期:2013-07-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,meta分析
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2006-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1978-02-28 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1996-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-10-30 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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pub_type: 杂志文章,随机对照试验
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更新日期:2007-12-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-12-0774
更新日期:2005-06-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
abstract::Increased plasma plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of vascular disease. In type 2 diabetes mellitus high PAI-1 levels are associated with increased plasma concentrations of free fatty acids (FFA) and triacylglycerol indicating an association or a causal relationship. To a...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2003-09-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-11-0707
更新日期:2005-03-01 00:00:00
abstract::Elucidation of the molecular defects responsible for antithrombin III deficiency is proceeding rapidly. In order that a record is kept of the new and duplicated mutations that are found, we have compiled a database that we plan to update annually. In this, the first report of the database, we list 6 antithrombin III l...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
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