Abstract:
:Recombinant forms of human antithrombin (AT) were expressed in COS-1 cells, and their interaction with human thrombin characterized by comparing the reactivity of two engineered mutant forms of AT with the wild-type recombinant. Both mutant forms contained single amino acid substitutions of Asp (G392D) or Pro (G392P) for the wild-type Gly, at residue 392, termed the P2 position with reference to the adjacent reactive centre bond. All three forms of AT co-migrated on Western blots, with an apparent molecular weight of 58 kD, with endoglycosidase F treatment reducing their mobility to 47 kD. The two mutant forms of AT reacted with thrombin differently from the wild-type molecule, in that the G392D substitution abrogated the thrombin inhibitory capacity of the protein, while the G392P substitution enhanced the reactivity of the recombinant mutant AT with thrombin. Under pseudo-first order conditions, the second order rate constants for the reaction of the recombinant wild-type and G392P mutant AT were determined to be 1.4 x 10(4) L-mol-1 sec-1 and 3.0 x 10(4) L-mol-1 sec-1, respectively, a difference of 210%. In contrast, in the presence of heparin, the reaction rates of the G392P and wild-type AT forms with thrombin, differed by less than 25%. We conclude that the P2 position of AT is an important residue for AT to express its inhibitory activity, alterations to which can either enhance or impair the inhibition of thrombin by AT.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Sheffield WP,Blajchman MAdoi
10.1016/0049-3848(94)90240-2subject
Has Abstractpub_date
1994-08-01 00:00:00pages
293-305issue
3eissn
0049-3848issn
1879-2472pii
0049-3848(94)90240-2journal_volume
75pub_type
杂志文章abstract:BACKGROUND:Deep vein thrombosis (DVT) is a common complication of acute stroke, but the new incidence in the era of improved specialist input in stroke care is yet unknown. The models for VTE diagnosis is well established, but prediction models to target at-risk patients for pharmacological prophylaxis is lacking and r...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2016.04.002
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:There is a substantial local release of tissue-type plasminogen activator (t-PA) in the splanchnic vascular bed, and this release is increased at high sympathetic tone. Coronary t-PA release is also significant, and this release increases during cardiac nerve stimulation and during reperfusion after 10 min o...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2009.10.004
更新日期:2010-03-01 00:00:00
abstract::We previously reported that the expression of thrombomodulin on the MEG-01, a cell line from human megakaryoblastic leukemia, was increased by agents that increase intracellular cAMP. In this paper we examine the effect of these agents on cultured human umbilical vein endothelial cells (HUVEC) and mouse hemangioma cel...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(91)90107-8
更新日期:1991-02-01 00:00:00
abstract:BACKGROUND:Intravenous fluids can impair coagulation and affect the endothelial glycocalyx, whereas glycocalyx shedding itself can cause an impairment of clot formation and firmness. We hypothesized that hydroxyethyl starch 6% (130/0.4) has a more distinct effect on coagulation and glycocalyx shedding than albumin 5%. ...
journal_title:Thrombosis research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.thromres.2019.10.020
更新日期:2019-11-01 00:00:00
abstract:INTRODUCTION:The TF-FVIIa complex is the primary activator of coagulation. Elevated levels of microvesicle (MV) bearing tissue factor (TF)-dependent procoagulant activity are detectable in patients with an increased risk of thrombosis. Several methods have been described to measure MV TF activity but they are hampered ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2019.07.011
更新日期:2019-10-01 00:00:00
abstract:UNLABELLED:Disturbances of coagulation and fibrinolysis have been reported in patients with chronic uremia. Studies of different coagulation and fibrinolysis parameters in regularly dialyzed patients have yielded conflicting results. Global fibrinolytic capacity (GFC) examines the function of the entire fibrinolytic sy...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2004.08.014
更新日期:2005-01-01 00:00:00
abstract:INTRODUCTION:The standard dabigatran etexilate dosage for prevention of venous thromboembolism (VTE) after elective total hip or knee replacement (THR/TKR) is 220mg once daily (qd), with 150mg qd for patients with moderate renal impairment. As clinical trial experience in patients with moderate renal impairment was lim...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
doi:10.1016/j.thromres.2016.05.014
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:Upon platelet stimulation with agonists, reactive oxygen species (ROS) generation enhances platelet activation and granule release. Whether ROS generation during platelet storage could be directly correlated with the expression of proinflammatory molecules and granule release has been investigated in this st...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2017.06.016
更新日期:2017-08-01 00:00:00
abstract:INTRODUCTION:Dermatan sulfate, a sulfated glycosaminoglycan, acts as an anticoagulant by accelerating the inhibition of thrombin by heparin cofactor II. MATERIALS AND METHODS:A low molecular mass dermatan sulfate was obtained by peroxy-radical depolymerization from a parent dermatan sulfate. Chemical characterization ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2007.09.001
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Postmenopausal hormone therapy is associated with many diseases and conditions, e.g., cardiovascular diseases and asthma, but the underlying molecular mechanisms are incompletely understood. The aim of the current study was to investigate the effect of four different postmenopausal hormone therapy regimens o...
journal_title:Thrombosis research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.thromres.2011.12.009
更新日期:2012-07-01 00:00:00
abstract::Patients with Familial Hyperlipoproteinaemia Type II showed evidence of increased platelet aggregability when compared to normal controls. This abnormality was not influenced by oral therapy with probucol whether or not the serum cholesterol levels were lowered during the study period. Probucol assays indicated adequa...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(82)90018-4
更新日期:1982-04-15 00:00:00
abstract::The concentration of tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1) and the complex of t-PA and PAI-1 (t-PA-PAI-1 complex) were measured using an enzyme immunoassay, where the first antibody was monoclonal antibody against PAI-1 and the second one was polyclonal anti-t-PA Fab' antibody....
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90392-7
更新日期:1989-09-01 00:00:00
abstract::Current therapies for treatment of hemophilia A involve infusion of factor VIII, but are ineffective for patients who develop inhibitory antibodies. We have previously proposed that bypassing the intrinsic pathway (VIIIa/IXa) with reversibly acylated factor Xa offers an improvement on existing therapies as it provides...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(97)00267-3
更新日期:1997-11-15 00:00:00
abstract::It has been suggested that unstable angina at rest, like acute myocardial infarction, might be associated with a thrombotic process. In order to study the hypothesis that myocardial ischemia during exercise could also be associated with an activation of blood coagulation and/or fibrinolysis, we investigated the presen...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90222-v
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment o...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/j.thromres.2004.05.009
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:Although risk of hospital-associated venous thromboembolism (HA-VTE) differs between critically and non-critically ill children, studies to date have not led to distinct, pragmatic risk scores. OBJECTIVE:To determine risk factors for HA-VTE in critically ill children not undergoing cardiothoracic surgery, i...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2015.04.036
更新日期:2015-10-01 00:00:00
abstract::The behavior of hemostatic system activation during protracted physical exercise is well known, but the duration of its modification is not yet defined. In order to evaluate the time of hemostatic system activation after prolonged strenuous endurance physical exercise (typical marathon race: 42.195 km, v=15.35 km/h; m...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(97)00293-4
更新日期:1998-01-15 00:00:00
abstract::We investigated the alteration of heparan sulfate proteoglycans induced by thrombin in cultured vascular endothelial cells. Heparan sulfate proteoglycans, which were metabolically labeled with [3H] glucosamine and [35S] sulfate, were isolated by DEAE-Sephacel ion-exchange chromatography and characterized by molecular ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(97)00257-0
更新日期:1997-11-01 00:00:00
abstract:BACKGROUND:Influencing factors for clopidogrel-mediated platelet inhibition have only been evaluated by one or two different test systems in the same population so far. Since previous studies revealed poor correlations between the various platelet function tests, the identification of influencing variables for clopidog...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2011.05.008
更新日期:2011-10-01 00:00:00
abstract:INTRODUCTION:Portal vein thrombosis (PVT) is a well-known complication in patients with liver cirrhosis (LC). The aim of this study is to investigate the outcomes of cirrhotic patients with PVT treated with low-molecular-weight heparin (LMWH). METHOD:Ninety-one LC patients with PVT were treated with dalteparin or enox...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2018.01.032
更新日期:2018-03-01 00:00:00
abstract::Use of low molecular weight heparins (LMWHs) is now generally accepted as an ideal method of prophylaxis against postoperative venous thromboembolism. However, the long-term effects on the development of postthrombotic deep vein insufficiency are not known. Every patient developing such complications consumes a vast a...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/0049-3848(95)00232-4
更新日期:1996-01-01 00:00:00
abstract:INTRODUCTION:D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations. MATERIALS AND METHODS:We conducted a ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.05.018
更新日期:2014-08-01 00:00:00
abstract::Heparinase degraded heparin fragments (HDHF) are enriched with a UV chromophore and can be utilized as calibrators to determine the molecular weight profile of low molecular weight heparins (LMWH's). In a standard protocol (1), the second to the last peak is assumed to be a hexasaccharide with a molecular weight of 1....
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90222-a
更新日期:1993-04-01 00:00:00
abstract:BACKGROUND:The "HERDOO2 rule" is a prospectively validated clinical decision rule used to identify low-risk women who can safely discontinue anticoagulants after completing 5-12 months of anticoagulant treatment for unprovoked venous thromboembolism. The VIDAS®d-Dimer (DD) assay, a component of the rule, was used in th...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2018.07.020
更新日期:2018-09-01 00:00:00
abstract::In this paper, we demonstrated that the procoagulant action of Lonomia achelous (Cramer) is due in part to a component that activates prothrombin. The activation by crude venom and Fractions obtained by gel filtration on Sephadex G-75 is not dependent of phospholipid, Ca++ or Factor V. The activation of prothrombin by...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90187-f
更新日期:1992-05-01 00:00:00
abstract:INTRODUCTION:Unfractionated heparin (UFH) does not cross the placenta and has demonstrated utility in the prevention and treatment of thrombosis during pregnancy. Limited information is available to guide initiation and monitoring of therapeutic UFH targeting an anti-Xa concentration of 0.3-0.7 u/ml during pregnancy. T...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2009.07.014
更新日期:2010-05-01 00:00:00
abstract:INTRODUCTION:Vitamin K antagonists are often used for anticoagulant treatment in hip fracture patients. The optimal handling with such anticoagulants is unclear. We aimed to determine when anticoagulation reversal occurred after vitamin K administration and how often prothrombin complex concentrates (PCCs) were adminis...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.10.031
更新日期:2014-01-01 00:00:00
abstract::The standard modality of administration of rFVIIa to patients with FVIII and FIX inhibitors is the intermittent infusion every 2 to 6 hours. No untoward local or systemic effects have been reported; laboratory data of activation of coagulation were reported in the presence of coexistent problems (sepsis, septic shock)...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(00)00220-6
更新日期:2000-07-01 00:00:00
abstract::The extrinsic pathway of coagulation is initiated when zymogen factor VII binds to its cell surface receptor tissue factor. Recently recombinant human tissue factor has become available and therefore in this study the direct binding of human factor VII in plasma to recombinant tissue factor was explored. Factor VII bi...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90103-u
更新日期:1993-05-15 00:00:00
abstract:INTRODUCTION:Pathogenesis of idiopathic pulmonary arterial hypertension (iPAH) includes endothelial dysfunction and in situ thrombosis. A hypercoagulable state has also been postulated but never demonstrated. Our objective was to determine whether patients with iPAH had a hypercoagulable state using calibrated automate...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.08.020
更新日期:2010-12-01 00:00:00