Abstract：
:Site directed mutagenesis was used to construct a t-PA variant that contains an additional glycosylation site in the first kringle domain (T103N) combined with a tetra-alanine substitution in the protease domain (KHRR 296-299 AAAA). This combination variant has a plasma clearance rate that is 4.5-fold slower in rats and 5.4-fold slower in rabbits than t-PA. It is also less than one tenth as active as t-PA towards plasminogen in the presence of fibrinogen, and has approximately twice the normal activity in the presence of fibrin. It shows substantial resistance to the fast acting inhibitor, plasminogen activator inhibitor-1 (PAI-1), requiring a 10-fold greater molar excess of PAI-1 to reduce its activity by 50%, compared to t-PA. This is the result of a reduction of nearly 100-fold in the second order rate constant for PAI-1 inactivation. These results show that it is possible to combine mutations in different domains of t-PA to construct a variant which is simultaneously slower clearing, less reactive towards plasminogen in the absence of a fibrin clot, and resistant to inactivation by PAI-1.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Paoni NF,Keyt BA,Refino CJ,Chow AM,Nguyen HV,Berleau LT,Badillo J,Peña LC,Brady K,Wurm FMsubject
Has Abstract,Author List Incompletepub_date
1993-08-02 00:00:00pages
307-12issue
2eissn
0340-6245issn
2567-689Xjournal_volume
70pub_type
杂志文章abstract：:This study explores the effects on some hematological parameters of a low-dose aspirin regimen (50 mg/day) versus a conventional aspirin treatment with reported antithrombotic efficacy (324 mg/day), in patients with acute myocardial infarction. Fifteen patients were randomized into 3 equal groups receiving 50 mg or 32...
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：1985-08-30 00:00:00
abstract：:An increased prevalence of hypertension is reported in haemophilia patients, but data from large, unbiased studies are lacking. The aim of our study was to cross-sectionally assess the prevalence of hypertension in a large cohort of 701 haemophilia patients. Blood pressure (BP) measurements performed in 386 Dutch and ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH12-05-0313
更新日期：2012-10-01 00:00:00
abstract：:Recombinant factor VIIa (rFVIIa: NovoSeven; Novo Nordisk) has proven efficacy in the treatment of haemophilic patients with inhibitors. This prospective, double-blind study compared rFVIIa (35 vs. 90 microg/kg) in the initiation and maintenance of haemostasis during and after elective surgery. Patients with inhibitors...
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：1998-11-01 00:00:00
abstract：:Despite great efforts in stroke research, disability and recurrence rates in ischaemic stroke remain unacceptably high. To address this issue, one potential target for novel therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity especially under high shear rates as it bridges ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1055/s-0038-1648251
更新日期：2018-06-01 00:00:00
abstract：:Fibrin D-Dimer (D-Di), prothrombin activation fragment (F 1+2) and thrombin-antithrombin III complexes (TAT) were measured using ELISA procedures in the plasma of patients with an acute deep venous thrombosis (DVT), at presentation and on days 2, 6 and 10 after initiation of heparin treatment. Patients were randomly a...
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：1993-12-20 00:00:00
abstract：:This study compares the ability of unmodified and carbohydrate-modified forms of factor VIII/von Willebrand factor (FVIII/vWF) protein to bind to platelets in the presence of ristocetin or thrombin. Treatment of intact FVIII/vWF with alpha-D-neuraminidase results in more than 95% desialylation. Asialo FVIII/vWF retain...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-06-24 00:00:00
abstract：:The aim was to investigate the perioperative risk of ischaemic and bleeding events in patients with coronary stents undergoing cardiac and non-cardiac surgery and how these outcomes are affected by the perioperative use of oral antiplatelet therapy. This was a multicentre, retrospective, observational study conducted ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,多中心研究
doi：10.1160/TH14-05-0436
更新日期：2015-02-01 00:00:00
abstract：:von Willebrand disease (VWD) is a quantitative or qualitative defect in von Willebrand factor (VWF) resulting in mucocutaneous bleeding symptoms and hemorrhage following hemostatic challenges, such as trauma or surgery. VWD-specific therapy, DDAVP (1-desamino-8-D-arginine vasopressin) and VWF concentrates, is necessar...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0040-1713636
更新日期：2020-08-01 00:00:00
abstract：:The urinary excretion rate of antithrombin III related antigen (AT III RA) was examined in cerebral stroke. The excretion rate of AT III RA in cerebral hemorrhage (CH) was 12.33 +/- 1.61 X 10(-4) ml/min. The patients with CH were further classified into two groups: in group CH-I, whose consciousness state was stupor o...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-12-29 00:00:00
abstract：:During treatment with vitamin K antagonists, International Normalized Ratios (INR) are determined periodically to maintain a therapeutic level of anticoagulation. We evaluated two existing methods for therapeutic quality control (linear interpolation and equidivision), with regard to their validity and reproducibility...
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：1999-10-01 00:00:00
abstract：:Recombinant human activated factor VII (rHuFVIIa) can reduce bleeding but may be associated with arterial thrombosis. We hypothesized that rHuFVIIa would increase the occurrence of cyclic flow reductions (CFR) and reduce intra-abdominal bleeding in an experimental model. An adapted Folts' model of carotid artery lesio...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2007-02-01 00:00:00
abstract：:Factor VIII inhibitors in mild haemophilia are uncommon and the management of such patients is controversial. The development of a persistently high responding F VIII inhibitor in a mild haemophiliac is reported and the behaviour of the inhibitor discussed in the context of the various therapeutic regimes employed for...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-08-31 00:00:00
abstract：:We have identified a patient with a dysfunctional prothrombin that we have designated Prothrombin Frankfurt. The proband was characterized by a prothrombin activity level of 13% and 20% compared to normal controls using two different assays with a normal prothrombin antigen level of 91% of normal controls. The genetic...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1995-02-01 00:00:00
abstract：:The multimeric plasma glycoprotein von Willebrand factor (VWF) is best known for recruiting platelets to sites of injury during primary hemostasis. Generally, mutations in the VWF gene lead to loss of hemostatic activity and thus the bleeding disorder von Willebrand Disease. By employing cone and platelet aggregometry...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/a-1344-4405
更新日期：2020-12-31 00:00:00
abstract：:Recombinant human factor VIIa (rFVIIa; NovoSeven) is a two-chain activated clotting factor that is used in the treatment of haemophilia. The distribution of radioactivity in male and pregnant and non-pregnant female rats has been examined by whole-body autoradiography (WBA) after single intravenous doses of 125I-radio...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:An alternative method of uniting small diameter vessels to obtain tissue union while limiting the thrombogenic effect of suture placement at a vessel anastomosis involves the use of a thrombin based fibrin glue as a surgical sealant. This investigation addresses whether the in vitro application of a thrombin based glu...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-08-01 00:00:00
abstract：:To determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTCA), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1992-02-03 00:00:00
abstract：:The alphaIIbeta3 receptor (GPIIb/IIIa) is the only platelet-specific integrin receptor and the most abundant adhesion/aggregation receptor on the surface of human platelets. Since mice are increasingly being used as models of human disease, we analyzed the structure and function of murine platelet alphaIIbeta3, utiliz...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：:Expression of isolated beta integrin cytoplasmic domains in cultured endothelial cells was reported to induce cell detachment and death. To test whether cell death was the cause or the consequence of cell detachment, we expressed isolated integrin beta1 cytoplasmic and transmembrane domains (CH1) in cultured human umb...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2005-11-01 00:00:00
abstract：:EPCR is a type I transmembrane protein, highly expressed on the endothelium of large vessels, that binds protein C and augments its activation. In this study, a 23bp insertion in the EPCR gene was found in 4/198 survivors of myocardial infarction and 3/194 patients with deep vein thrombosis. The EPCR gene with the ins...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：BACKGROUND: Clinical effectiveness of recombinant human soluble thrombomodulin (rhTM) in sepsis or sepsis-induced coagulopathy remains a matter of dispute. Recently, the Sepsis Coagulopathy Asahi Recombinant LEThrombomodulin (SCARLET) trial, the latest multinational multi-centre phase III randomized controlled trial, w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,meta分析
doi：10.1055/s-0038-1676345
更新日期：2019-01-01 00:00:00
abstract：:Although there is considerable evidence that platelet activation is associated with polymerization of actin, it is not known whether there is some pre-existing F-actin even before activation. We have examined the state of actin polymerization in nonactivated platelets by deoxyribonuclease assay of G-actin and total ac...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1982-10-29 00:00:00
abstract：:Our initial finding that CD40- and CD40 ligand (CD40L)-deficient mice displayed prolonged tail bleeding and platelet function analyzer (PFA-100) closure times prompted us to further investigate the role of the CD40-CD40L dyad in primary hemostasis and platelet function. Recombinant human soluble CD40L (rhsCD40L), chem...
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
abstract：:Monitoring of anti-factor Xa activity is often performed during treatment with low-molecular-weight heparins (LMWHs) in pregnancy because the anticoagulant effect may decrease as pregnancy progresses, but assays for anti-factor Xa activity are unavailable in many clinical institutions caring for pregnant women. Heptes...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH08-09-0560
更新日期：2009-11-01 00:00:00
abstract：:Heparin-induced thrombocytopenia (HIT), a relatively common complication of heparin therapy, results of platelet activation, via the receptor for the Fc domain of IgG (FcgammaRIIa), by heparin-dependent-antibodies, commonly directed against the heparin-platelet factor 4 (H-PF4) antigenic complex. Our strategy was to u...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-06-01 00:00:00
abstract：:The clinical impact of in-stent thrombosis is high because it is associated with high mortality and 20 % of the patients suffer a recurrent event within the two following years. The aim of this study was to characterise the morphologic and proteomic profile of in-stent thrombi (IST) in comparison to thrombi developed ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-03-069
更新日期：2017-08-30 00:00:00
abstract：:Computer-assisted oral anticoagulant dosage is being increasingly used to meet growing demands for oral anticoagulation. The DAWN AC is one of the most widely used computer-dosage programs. Evidence of its value and that of other computer programs has been based previously only on laboratory evidence of "time in targe...
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：:Herpes simplex virus (HSV) infection is histopathologically associated with vascular injury, fibrinoid necrosis and inflammatory cell infiltrates. We have previously shown in vitro that HSV infection of human umbilical vein endothelial cells (HUVEC) promotes a procoagulant phenotype manifest by the induction of tissue...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:Congenital afibrinogenemia and severe hypofibrinogenemia are severe bleeding disorders characterized by either undetectable or very low levels of fibrinogen in patients' plasma and platelets. A majority of the reported cases are caused by mutations in the fibrinogen Aalpha chain. In this study, we identified a genetic...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH06-01-0020
更新日期：2006-06-01 00:00:00
abstract：:We performed experiments to determine whether endothelial cells synthesize phospholipid metabolites via the lipoxygenase pathway and whether these metabolites influence platelet/vessel wall interactions. Monolayers of cultured human endothelial cells were incubated with 14C-arachidonic acid and their cyclo-oxygenase a...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-06-24 00:00:00
