Abstract:
:Although intravital microscopy models of thrombosis in mice have contributed to dissect the mechanisms of thrombus formation and stability, they have not been well adapted to study long-term evolution of occlusive thrombi. Here, we assessed the suitability of the dorsal skinfold chamber (DSC) for the study of thrombolysis and testing of thrombolytic agents by intravital microscopy. We show that induction of FeCl3-induced occlusive thrombosis is achievable in microvessels of DSCs, and that thrombi formed in DSCs can be visualised by intravital microscopy using brightfield transmitted light, or fluorescent staining of thrombus components such as fibrinogen, platelets, leukocytes, and von Willebrand factor. Direct application of control saline or recombinant tissue-plasminogen activator (rtPA) to FeCl3-produced thrombi in DSCs did not affect thrombus size or induce recanalisation. However, in the presence of hirudin, rtPA treatment caused a rapid dose-dependent lysis of occlusive thrombi, resulting in recanalisation within 1 hour after treatment. Skin haemorrhage originating from vessels located inside and outside the FeCl3-injured area was also observed in DSCs of rtPA-treated mice. We further show that rtPA-induced thrombolysis was enhanced in plasminogen activator inhibitor-1-deficient (PAI-1-/-) mice, and dropped considerably as the time between occlusion and treatment application increased. Together, our results show that by allowing visualization and measurement of thrombus lysis and potential bleeding complications of thrombolytic treatments, the DSC provides a model for studying endogenous fibrinolysis and for first-line screening of thrombolytic agents. Furthermore, using this system, we found that thrombin and clot aging impair the thrombolytic action of rtPA towards FeCl3-produced thrombi.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Boulaftali Y,Lamrani L,Rouzaud MC,Loyau S,Jandrot-Perrus M,Bouton MC,Ho-Tin-Noé Bdoi
10.1160/TH11-10-0705subject
Has Abstractpub_date
2012-05-01 00:00:00pages
962-71issue
5eissn
0340-6245issn
2567-689Xpii
11-10-0705journal_volume
107pub_type
杂志文章abstract::Tissue plasminogen activator (tPA) activity in blood and blood plasma has been difficult to determine because it is unstable, especially in subjects with high levels of plasminogen activator inhibitor type 1 (PAI-1). We have attempted to stabilize the tPA activity by collecting 9 volumes of blood in 1 volume acidic ci...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-11-24 00:00:00
abstract::Idarucizumab, a Fab fragment directed against dabigatran, produced rapid and complete reversal of the anticoagulation effect of dabigatran in animals and in healthy volunteers. The Study of the REVERSal Effects of Idarucizumab in Patients on Active Dabigatran (RE-VERSE AD™) is a global phase 3 prospective cohort study...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH15-03-0192
更新日期:2015-07-01 00:00:00
abstract::Recently we prepared sulfated, low-molecular-weight lignins (LMWLs) to mimic the biological activities of heparin and heparan sulfate. Chemo-enzymatically prepared sulfated LMWLs represent a library of diverse non-sugar, aromatic molecules with structures radically different from the heparins, and have been found to p...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH09-07-0454
更新日期:2010-03-01 00:00:00
abstract::Plasma levels of D-dimer have been found useful as a marker of deep venous thrombosis in those patients in whom thrombosis is suspected, but their usefulness in postoperative screening is less clear. We have investigated the relationship of D-dimer to deep venous thrombosis in 90 patients after total hip and knee arth...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Extrinsic coagulation pathway inhibitor may be an important regulator of haemostasis to prevent thrombosis after tissue damage. The functional activity of this inhibitor was determined using a chromogenic substrate assay, and compared to the activities of antithrombin, heparin cofactor II and protein C during the peri...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-11-24 00:00:00
abstract::D-Dimer measurements are being increasingly used for negative prediction of deep vein thrombosis (DVT). At our institution, clinical score, D-Dimer assay, plethysmography and, if necessary, Doppler ultrasound are used to secure the diagnosis. We collected the data from 100 consecutive patients proven to have DVT. We e...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH03-11-0699
更新日期:2004-06-01 00:00:00
abstract::Biosynthesis of the adhesive glycoprotein von Willebrand factor (vWf) by endothelial cells results in constitutive secretion of small multimers and storage of the largest multimers in rod-shaped granules called Weibel-Palade bodies. This pattern is reproduced by expression of pro-vWf in heterologous cells with a regul...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-12-20 00:00:00
abstract::Electronic free platelet counting was more sensitive than turbidimetry to detect collagen-induced platelet activation in human platelet-rich plasma. Purified human C1q exhibited a greater inhibitory effect on collagen-induced platelet aggregation in turbidimetry than free platelet counting. Because the change from sma...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1987-08-04 00:00:00
abstract::We performed a DNA analysis on a patient with severe type I factor VII deficiency by the polymerase chain reaction amplification and a direct DNA sequencing method. The proband was a 66-year-old Japanese woman who had recurrent episodes of excessive bleeding after dental extraction. The functional and antigenic levels...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::Omega-3 fatty acids (n-3 FA) may reduce atherogenesis and thrombosis. We investigated the effects of n-3 FAs on procoagulant activity and cytokine expression in whole blood cultures from patients with atherosclerosis. Eleven of the 23 included patients had received 5.1 g n-3 FA daily for 6 months (group I) whereas 12 ...
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:1999-04-01 00:00:00
abstract::Plasminogen activator inhibitor-1 (PAI-1) is a unique member of the serpin family, as it spontaneously converts into a latent conformation. However, the exact mechanism of this conversion is not known. Previous studies reported that neutralizing monoclonal antibodies as well as reversal or removal of charges on the s3...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::The blockade of platelet membrane glycoprotein IIb/IIIa by a monoclonal antibody, 7E3, was measured by flow cytometry using a fluorescein isothiocyanate-conjugated disintegrin, FITC-crotavirin, as the probe. After treatment of platelets with 7E3 or 7E3 F(ab')2, there is a good correlation between the inhibition of pla...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::A group of 90 hemophiliacs who had been regularly treated with non virus-inactivated factor VIII or IX concentrates were studied in 1983. At that time 50 patients were HIV-1-antibody positive, 6 additional seroconversions occurred until 1985. 26 of the 50 patients seropositive in 1983 are currently asymptomatic. 4 pat...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-06-30 00:00:00
abstract::Growing evidence indicates that rheumatoid arthritis (RA) is associated with an increased risk for thromboembolic cardiovascular events. We investigated thrombin generation profiles in RA patients and their dependence on plasma factor/inhibitor composition. Plasma factor (F) compositions (II, V, VII, VIII, IX, X), ant...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-02-0091
更新日期:2010-08-01 00:00:00
abstract::Limited data exist on thrombophilia and the risk of venous thrombosis (VT) during pregnancy and postpartum. The objectives of the present study were to investigate the role of haemostatic risk factors for pregnancy-related VT and their phenotypic expression in deep-vein thrombosis (DVT) and pulmonary embolism (PE). To...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-05-0350
更新日期:2012-12-01 00:00:00
abstract::It is widely anticipated that large platelets are more reactive than small platelets. This was mainly shown in Ca2+-poor media albeit extracellular Ca2+ is utilized by platelets for activation. We determined the impact of extracellular Ca2+ on functional differences between large and small platelets in response to thr...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1712447
更新日期:2020-07-01 00:00:00
abstract::A suggestive locus on chromosome 8 could be shown to be associated with familial high factor VIII (FVIII) levels in venous thromboembolism. The ADAMDEC 1 gene is a candidate expressing an ectodomain sheddase. However, the ectodomain of the clearance receptor for FVIII, the low-density lipoprotein receptor-related prot...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH08-01-0059
更新日期:2008-05-01 00:00:00
abstract::The acidic mucopolysaccharide extracted from sea cucumber (Stichopus japonicus Selenka) (SJAMP) has been shown to cause platelets to aggregate. Using citrated platelet-rich plasma (PRP), washed platelets and formaldehyde-fixed platelets from humans, we investigated the effects of platelet inhibitors and various plasma...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-06-16 00:00:00
abstract::Edoxaban is an oral, direct, once-daily, factor Xa inhibitor developed for stroke prevention in patients with atrial fibrillation and for the treatment and secondary prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism. Among elderly patients who require anticoagulation the...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,随机对照试验
doi:10.1160/TH14-06-0547
更新日期:2015-04-01 00:00:00
abstract::Cardiovascular diseases are a major cause of mortality in the developed world. Efficacy of thrombolysis plays an important role in the management of acute myocardial infarction and cerebral insult both in the acute event and in the long-term outcome of these patients. New adjunctive strategies have been tested, theref...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH04-12-0818
更新日期:2005-07-01 00:00:00
abstract::A randomised, prospective, double-blind trial was performed, to compare the safety and efficacy of a new low-molecular-weight heparin (LMWH) Bemiparin and standard unfractionated heparin (UFH), for the prophylaxis of postoperative venous thromboembolism. 300 patients scheduled to undergo elective hip arthroplasty were...
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:2000-04-01 00:00:00
abstract::Anticoagulant control facilities are being overwhelmed by requests for monitoring and large numbers of patients are not therefore receiving treatment. Procedures designed for point-of-care testing have therefore been developed, the most popular being the CoaguChek. The need for external quality assessment (EQA) of mon...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH09-10-0683
更新日期:2010-05-01 00:00:00
abstract::Retinal vein occlusion (RVO) is the most common retinal vascular disorder second to diabetic retinopathy. The main risk factors in patients with RVO are hypertension, diabetes, hyperlipidemia, increased blood viscosity and glaucoma. The pathogenesis of RVO has not yet been clarified. In these events platelets could pl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-02-01 00:00:00
abstract::Analysis of platelet membrane proteins and glycoproteins by SDS polyacrylamide gel electrophoresis was carried out before and after treatment with thrombin. Extended incubation with thrombin (in the presence of EDTA or adenosine, which inhibit aggregation) produced extensive changes in the bands observed. With incuba...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1977-06-30 00:00:00
abstract::Vascular endothelial cells perform many differentiated functions in processes such as angiogenesis, hemostasis, and inflammation. The number of recognized differentiated functions has increased rapidly in recent years, but there may be many more still unrecognized. The purpose of this study is to estimate the fraction...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1993-05-03 00:00:00
abstract::Restenosis following successful percutaneous coronary revascularization continues to represent a major problem limiting the clinical efficacy of this procedure. The underlying mechanisms of restenosis are comprised of a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 00:00:00
abstract::Dabigatran is an oral, reversible thrombin inhibitor that has shown promising results in large clinical trials. Laboratory monitoring is not needed but the effects on common coagulation assays are incompletely known. Dabigatran was added to plasma from healthy subjects in the concentration range 0-1,000 μg/l and analy...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH10-06-0342
更新日期:2011-02-01 00:00:00
abstract::Unfractionated heparin is the most commonly used anticoagulant in ST-elevation myocardial infarction (STEMI) and its effect can be monitored with activated partial thromboplastin time (aPTT). However, the optimal aPTT range during heparin therapy after primary percutaneous coronary intervention (PCI) is yet to be defi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH12-10-0726
更新日期:2013-05-01 00:00:00
abstract::Diabetic subjects have been shown to have altered fibrin network structures. One possible cause may be fibrinogen glycation resulting in altered structure/function properties. We investigated the effect of glucose control on fibrinogen glycation and fibrin network structure in type 2 diabetes. Blood samples were taken...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2006-11-01 00:00:00
abstract::Plasminogen activator inhibitor type-1 (PAI-1) is a physiologic modulator of the fibrinolytic system. We have shown previously that PAI-1 biosynthesis in cultured cells depends on several factors in serum. Because platelets are richly endowed with specific growth factors and because the release reaction is an integral...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00