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 that the Gla-domain-dependent interaction of FIXa and FX with PCPS in the presence of FVIIIa positions the active-site of the protease at an appropriate height above the membrane surface to optimise the catalytic reaction. In this study, we investigated the contribution of the NH2-terminal EGF-domain (EGF1) of FIXa to the recognition specificity of intrinsic tenase by constructing an EGF1 deletion mutant of FIXa (FIXa-desEGF1) and characterising the properties of the mutant in kinetic, direct binding and FRET assays. The results of direct binding and kinetic studies demonstrated that the binding affinity of the mutant for interaction with FVIIIa on PCPS has been impaired greater than 10-fold and the catalytic efficiency of the mutant protease-FVIIIa-PCPS complex in the activation of FX has been decreased ~100-fold. By contrast, the mutant protease exhibited a normal activity toward FX in the absence of the protein cofactor. FRET measurements revealed that the distance of the active-site of the mutant FIXa relative to PCPS vesicles has been decreased 10 Å from 75 ± 2 Å for FIXa to 65 ± 2 Å for FIXa-desEGF1 independent of FVIIIa. These results suggest that the NH2-terminal EGF-domain of FIXa provides a binding-site for FVIIIa and plays an essential spacer function in the intrinsic tenase complex.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Qureshi SH,Yang L,Rezaie ARdoi
10.1160/TH12-06-0436subject
Has Abstractpub_date
2012-12-01 00:00:00pages
1154-64issue
6eissn
0340-6245issn
2567-689Xpii
12-06-0436journal_volume
108pub_type
杂志文章abstract：:Low molecular weight heparin (LMWH) is used increasingly for prophylaxis and treatment of venous thromboembolism during pregnancy. However, the prophylactic dose for patients at moderate risk varies between centers, and the recommended LMWH dose for the non pregnant patient is frequently used in pregnant women. The ai...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-10-0618
更新日期：2004-10-01 00:00:00
abstract：:Subcutaneous heparin is the treatment of choice for women requiring anticoagulant therapy during pregnancy. However, heparin therapy presents a management problem at delivery because of its potential to cause a persistent anticoagulant effect and thus increase the risk of bleeding. In order to avoid therapeutic compli...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-03-04 00:00:00
abstract：BACKGROUND:Recombinant hirudin, a pure, specific antithrombin could be more effective than heparin in the treatment of deep vein thrombosis, but its short half-life requires constant intravenous infusion, whereas subcutaneous administration of recombinant hirudin can ensure stable and prolonged plasma levels. The aim o...
journal_title：Thrombosis and haemostasis
pub_type： 临床试验,杂志文章
doi：
更新日期：1994-05-01 00:00:00
abstract：:The efficacy and safety of dabigatran for treatment of venous thromboembolism (VTE) were demonstrated in two trials. It is unclear if the results pertain to patients with cancer and VTE. Data from two randomised trials comparing dabigatran and warfarin for acute VTE were pooled. Primary efficacy outcome was symptomati...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH14-11-0977
更新日期：2015-07-01 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
abstract：BACKGROUND:Elevated von Willebrand factor (vWF) is a risk factor in the development of acute myocardial infarction. The importance of vWF and factor VII:C in the pathogenesis of cerebrovascular disease (CVD) is poorly defined. METHODS AND RESULTS:We studied 208 cases of stroke whose pathological type was defined by cr...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
abstract：:The contribution of the various components of the contact system in the generation of factor XIIa (FXIIa) and of kallikrein (KRN) on an electronegative surface and the release of the generated enzymes to the bulk phase was examined in mixtures of normal human plasma and plasmas congenitally deficient in these componen...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-09-01 00:00:00
abstract：:The esterase activity of highly purified human urokinase on Nalpha-acetylglycl-L-lysine methyl ester is strongly inhibited by 1 X 10(-5) to 1 X 10(-2)M Cu++, Hg++, Ni++, Co++, Fe+++, and Mn++ solutions, whereas Na+, K+, Ca++, and Mg++ are weakly effective. This inhibition is parallel with the inhibition of activation ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1978-02-28 00:00:00
abstract：:Although, the main physiological role of monocytes is attributed to innate immunity (that is, phagocytosis) and the development of tissue macrophages and dendritic cells, the pathophysiological role of these goes far behind these (simplistic) limits. Indeed, monocytes constitute a major source of blood tissue factor, ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH09-01-0023
更新日期：2009-11-01 00:00:00
abstract：:Imaging methods based on time-lapse microscopy are important tools for studying the dynamic events that shape thrombus formation upon vascular injury. However, there is a lack of methods to translate the vast amount of visual data generated in such experiments into quantitative variables describing platelet movements ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1055/s-0038-1668151
更新日期：2018-09-01 00:00:00
abstract：:The prophylactic treatment of haemophilia B and the management of haemophilia A or B with inhibitors demand frequent administrations of coagulation factors due to the suboptimal half-lives of the products commercially available and currently in use, e.g. recombinant factor IX (rFIX) and recombinant factor VIIa (rFVIIa...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH13-03-0213
更新日期：2013-11-01 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：:Lipid oxidation products and in particular oxidized phospholipids (OxPL) are increasingly recognized as inducers of chronic inflammation characteristic of atherosclerosis. OxPL stimulate production of chemokines and adhesion of monocytes to endothelial cells. However, accumulating data suggest that, in addition to the...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2007-03-01 00:00:00
abstract：:Tissue-type plasminogen activator (t-PA) is a fibrin-specific agent which is used to treat acute myocardial infarction. Pharmacokinetically, t-PA is characterized by a rapid clearance from the circulation. In a previous study, we constructed variant forms of t-PA with genetic modifications at the fibronectin finger-li...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:Among the nine ellagitannins, rugosin E was the most potent platelet aggregating agent with an EC50 of 1.5 +/- 0.1 microM in rabbit platelets and 3.2 +/- 0.1 microM in human platelets. The aggregations caused by rugosin E and ADP were inhibited by EGTA, PGE1, mepacrine, sodium nitroprusside and neomycin, but not by in...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-03-01 00:00:00
abstract：:It was the objective of this study to determine whether reduced cleavage of von Willebrand factor (VWF) multimers following aortic valve replacement (AVR) is a consequence of reduced shear stress or postoperative changes in VWF cleavage protease (ADAMTS-13) activity. Aortic stenosis (AS) may be complicated by acquired...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH11-12-0803
更新日期：2012-07-01 00:00:00
abstract：:Induction of procoagulant factors in malignant cells is considered to be the major cause of coagulation disorders in cancer. Thrombomodulin (TM), a negative regulator of coagulation was also found to be expressed in cancer cells. We report here evidence for another anticoagulant, the endothelial cell protein C recepto...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-02-01 00:00:00
abstract：:Previous studies have reported that the platelets of healthy term neonates have either diminished or normal reactivity compared to the platelets of adults. To circumvent the methodologic problems of previous studies, we used a whole blood flow cytometric method to study neonatal platelet reactivity to thrombin, a comb...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:In order to explore the mechanisms leading to conformational changes of the vitronectin receptor alphavbeta3 following ligand or divalent cation binding, we have investigated the expression of epitopes known as ligand-induced binding sites (LIBS) on beta3 cytoplasmic tail mutants expressed in CHO cells. Truncation of ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:Antiphospholipid-protein antibodies (APA) include lupus-type anticoagulant (LA) and antibodies recognizing complexes of anionic phospholipids (e.g. cardiolipin) and proteins (e.g. prothrombin and beta2-glycoprotein I). The presence of APA is associated with an increased risk of both arterial and venous thrombosis. How...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:The clinical benefits of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been shown in many trials. However, the mode of action of heparin has not been fully elucidated. Thus, we wanted to study the effects of UFH and LMWH in vivo by measuring coagulation activation markers in blood obtained ...
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：1994-12-01 00:00:00
abstract：:Tissue factor is a cellular receptor that initiates blood coagulation. The TF gene is constitutively expressed in some extravascular cell types and is inducibly expressed in several vascular cell types, including monocytes, vascular endothelial cells and vascular smooth muscle cells. Functional studies indicate that S...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1997-07-01 00:00:00
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journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH17-02-0087
更新日期：2017-08-30 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
abstract：:The spleen is a crucial organ in humans. However, little is known about the association of venous thromboembolism (VTE) with splenic injury and splenectomy in trauma patients. The aim of this study was to determine the subsequent risk of VTE following splenic injury and splenectomy. A nationwide retrospective cohort s...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH15-05-0381
更新日期：2016-01-01 00:00:00
abstract：:Circulating endotoxin is elevated in sepsis and plays a role in endothelial dysfunction whereas antithrombin is decreased by virtue of its consumption during complex formation with clotting factors and by proteolytic degradation by granulocyte elastase. Dysfunction of endothelium results in enhanced leukocyte rolling ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-03-0184
更新日期：2003-12-01 00:00:00
abstract：:Previously, we demonstrated in a rat model of heparin-induced osteoporosis that low molecular weight heparin (LMWH) produces less bone loss than unfractionated heparin, and that only heparin increases osteoclast number and activity. In contrast, both heparin and LMWH were found to decrease osteoblast function to a sim...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1998-09-01 00:00:00
abstract：:Parameters of the fibrinolytic system were studied in a primate model where the generation of thrombin was promoted in vivo. The procoagulant stimulus used was a combination of human factor Xa in combination with phosphatidylcholine/phosphatidylserine lipid vesicles (PCPS) as the source of coagulant active phospholipi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-06-28 00:00:00
abstract：:Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein however the mechanisms by which Lp(a) promote the atherosclerotic process are not clear. The apolipoprotein(a) portion of Lp(a) shares partial homology with plasminogen, a finding that has stimulated numerous studies. Lp(a) binds to fibrin and the affinity between f...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：1995-07-01 00:00:00
abstract：:Paired blood samples were obtained from mothers (venous) and babies (cord venous blood) at the time of delivery by caesarean section under epidural anaesthetic. Fetal platelets failed to aggregate in response to adrenaline in vitro although adrenaline could potentiate the threshold response to adenosine diphosphate (1...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-02-18 00:00:00
