Abstract:
:Platelet-rich clots are inefficiently lysed by current fibrinolytic agents. Platelets contain a great deal of plasminogen activator inhibitor 1 (PAI-1), the principal endogenous inhibitor of tissue-type plasminogen activator (t-PA). We have tested whether PAI-1 resistant t-PAs would be more effective thrombolytic agents in an in vitro model of platelet-rich clots. Clots were formed with recalcified human plasma without or with the addition of platelets. The lysis of these clots was followed by the release of incorporated 125I-fibrinogen. Mutant and wild-type t-PA were almost equally effective against clots lacking platelets but the mutant was twice as effective at lysing platelet-rich clots. A mechanism for this effect is suggested by the demonstration that a complex between wild-type t-PA and extruded platelet contents resembles that between purified t-PA and PAI-1 and that the PAI-1 resistant t-PA does not interefer with formation of this adduct. Because of its enhanced ability to lyse platelet-rich clots in vitro, further in vivo work may find that PAI-1 resistant t-PA is a more efficacious therapeutic agent than wild-type t-PA in situations where platelets contribute to the failure of thrombolysis.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Shohet RV,Spitzer S,Madison EL,Bassel-Duby R,Gething MJ,Sambrook JFsubject
Has Abstractpub_date
1994-01-01 00:00:00pages
124-8issue
1eissn
0340-6245issn
2567-689Xjournal_volume
71pub_type
杂志文章abstract::In patients with deep vein thrombosis (DVT), the factors which predispose to concomitant symptomatic pulmonary embolism (PE) have remained uncertain. From a prospective cohort of 5,451 consecutive patients with ultrasound-confirmed DVT, we analyzed 4,211 patients with a known status for presence (n=639) or absence (n=...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-09-0587
更新日期:2005-03-01 00:00:00
abstract::Factor IXa (FIXa) is a vitamin K-dependent coagulation serine protease which binds to factor VIIIa (FVIIIa) on negatively charged phospholipid vesicles (PCPS) to catalyse the activation of factor X (FX) to factor Xa (FXa) in the intrinsic pathway. Fluorescence resonance energy transfer (FRET) studies have indicated th...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-06-0436
更新日期:2012-12-01 00:00:00
abstract::Current thrombolytic strategies have a number of important shortcomings including resistance to recanalization and development of acute reocclusion. The purpose of this study was to investigate whether the lysis of venous thrombi by streptokinase could be enhanced by SR 46349, a novel 5-HT2 receptor antagonist, or clo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Plaque rupture followed by thrombosis is the underlying cause of the majority of acute coronary syndromes. Circulating microparticles (cMPs), membrane blebs released into blood by activated cells, have been associated to vascular diseases. Specifically, high levels of platelet-derived microparticles (pMPs) have been f...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-07-0486
更新日期:2012-12-01 00:00:00
abstract::Using a monoclonal antibody-based assay, we measured the fibrin degradation product release in the supernatant of plasma clots obtained before and after venous occlusion (VO) in 30 patients with definite or suspected vascular thrombosis (19 definite and 2 suspected deep vein thrombosis, 6 recurrent superficial thrombo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-02-19 00:00:00
abstract::The effects of etamsylate on human platelet aggregation and ATP release as well as on the arachidonate metabolism by the platelet have been studied. Etamsylate enhanced these platelet functions induced by arachidonic acid (AA), thromboxane A2, collagen and calcium ionophore A23187 but not those induced by ADP and epin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1982-12-27 00:00:00
abstract::We investigated changes in both thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels and its functional effect on in vitro fibrinolysis in normal pregnancy. 152 pregnant women and 31 women in the immediate postpartum period were studied, with pregnancy divided into 6 windows at 4 weekly intervals. As TAFI...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH04-06-0387
更新日期:2004-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::The aim of this study was to investigate the anti-thrombotic effects of an inhibitor of the plasminogen activator inhibitor-1 (PAI-1) in rats given endotoxin. In studies in vitro, PRAP-1, a Fab-fragment of a polyclonal antibody against human PAI-1, was shown to inhibit PAI-1 activity in rat plasma as well as to stimul...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH05-05-0313
更新日期:2005-11-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH07-08-0528
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND:Measurements of prothrombin fragment 1+2 (F1+2), thrombin antithrombin III complexes (TAT) and D-dimer plasma levels have been proposed as non-invasive screening tests to exclude postoperative deep venous thrombosis (DVT). We investigated the diagnostic efficacy of these coagulation activation markers to rul...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1998-03-01 00:00:00
abstract::Seasonal variation in venous thromboembolism (VTE) risk in individuals with familial predisposition to VTE has not been explored. This nationwide study aimed to determine whether there are age- and sex-specific seasonal differences in risk of hospitalisation of VTE among individuals with and without a family history o...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-04-0320
更新日期:2013-12-01 00:00:00
abstract::We studied a murine monoclonal antibody (211 A6) to von Willebrand factor (vWF) with a view to investigating structure-relationship of plasma vWF. The specificity of this antibody has been substantiated by ELISA tests and indirect immunofluorescence. It reacts with purified vWF, normal plasma but not with plasma or pl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-06-03 00:00:00
abstract::Complement C3 is a novel risk factor for cardiovascular disease (CVD), but the underlying mechanism is currently unknown. We determined the associations of the anaphylatoxin C3a, the activation product of C3, and of C3 itself with estimates of atherosclerosis and CVD. We studied associations of C3a and C3 with carotid...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-10-0831
更新日期:2014-06-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH04-01-0023
更新日期:2004-06-01 00:00:00
abstract::The gel-chromatography of the beta-alanine precipitate of human plasma and of purified fibrinogen shows the presence of different classes of fibrinogen complexes. A first class of complexes is detectable in correspondence with the ascending branch of the fibrinogen peak ("shoulder" complexes or high molecular weight f...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1657059
更新日期:1979-07-01 00:00:00
abstract::We analyzed the protein C gene (PROC) with the denaturing gradient gel electrophoresis (DGGE) scanning strategy in a series of 129 patients with suspected protein C (PC) deficiency (93 with low plasma PC levels and 36 with borderline level). At least one sequence variation was found in 104 of the 129 patients. Thirty-...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::A fully representative and viable platelet population was isolated from the blood of 15 baboons by a multiwash procedure, and labelled with In-111-oxine. The recovery of the total platelet population in the circulation was 85% +/- 9. Mean platelet life span was 146 hr +/- 13. Correcting for plasma radioactivity (alway...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-06-24 00:00:00
abstract::Thirty-two patients with acute, proximal-vein thrombosis were treated with heparin and alteplase (0.25 versus 0.5 mg/kg/24 h during 3-7 days) in a randomized, double-blind, multicenter, European (ETTT) trial. The treatment resulted in a decrease of the venographic Marder's score from 18 (6-25) to 13 (2-24) units (medi...
journal_title:Thrombosis and haemostasis
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1992-03-02 00:00:00
abstract::Shear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with u...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-12-0854
更新日期:2010-09-01 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:10.1160/TH16-02-0118
更新日期:2016-08-01 00:00:00
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journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH13-11-0941
更新日期:2014-09-02 00:00:00
abstract::Thrombocytopenia occurred in 11.6% of 43 patients prospectively randomized to receive either bovine lung or porcine mucosal heparin. Four patients received bovine heparin and developed mild to moderate thrombocytopenia after eight to twelve days which resolved when therapy was stopped in one to six days. One patient r...
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:1980-02-29 00:00:00
abstract::The effect of IgGs from 4 patients with antiphospholipid antibodies and elevated excretion of urinary 11-dehydro-thromboxane B2 was evaluated on the production of prostacyclin by human endothelial cells in culture. After 6 h incubation, there was no change in 6-keto-prostaglandin F1 alpha in the supernatant. However p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::Thrombotic complications are frequently associated with atherosclerosis. Lysophosphatidylcholine (LPC), a component accumulated in oxidatively modified LDL (ox-LDL), is known to play a crucial role in the initiation and progression of atherosclerotic vascular lesions. Since a vascular anticoagulant, tissue factor path...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::The still living members of the original bleeder family on the Aland Islands described by von Willebrand in 1926 have been reinvestigated by using modern laboratory techniques for the measurement of the Factor VIII complex and with regard to platelet aggregation. The low level of F VIII : C activity demonstrated in 19...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1981-02-23 00:00:00
abstract::We have evaluated the effect of plasminogen activators (t-PA and urokinase) on an experimental model of disseminated intravascular coagulation (DIC) in rabbits by injection of 20 micrograms/kg/h of E. coli lipopolysaccharide during 6 h t-PA (0.2 mg/kg and 0.7 mg/kg), urokinase (3000 U/kg/h) and saline (control) were g...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Despite reports that Tris [tris (hydroxymethyl)aminomethane] affects platelets, it is often used to buffer suspending media. Human or rabbit platelets were washed and resuspended in Tyrode solution containing apyrase and 0.35% albumin. Addition of 15 mM Tris partially inhibited primary aggregation induced by 10 microM...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-04-30 00:00:00
abstract::Bernard-Soulier syndrome is a rare congenital platelet disorder that affects a surface membrane adhesion receptor, glycoprotein (GP) Ib-V-IX. Both the genetic defects and the bleeding diatheses associated with the syndrome are heterogeneous due, in part, to the complexity of the involved receptor which consists of fou...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-11-01 00:00:00