Abstract：
:The inability of the heparin-antithrombin complex to inhibit fibrin-bound thrombin limits the utility of heparin for treatment of arterial thrombosis. In contrast with heparin, melagatran, a direct thrombin inhibitor (DTI), is equally effective at inhibiting fluid-phase thrombin and thrombin bound to fibrin. This reflects the ability of melagatran, a reversible, active site-directed DTI, to access the active site of thrombin even when it is fibrin-bound. Because bivalent DTIs, such as hirudin, compete with fibrin for access to the fibrin-binding site on thrombin, bivalent DTIs produce less inhibition of fibrin-bound thrombin than free thrombin when given in low doses. Consequently, higher doses of hirudin are needed for complete inhibition of fibrin-bound thrombin resulting in a steep dose-response curve. This phenomenon, combined with the fact that hirudin irreversibly inhibits thrombin, may account for hirudin's narrow therapeutic window. In a rabbit arterial thrombosis prevention and ear bleeding model, melagatran produced less bleeding than hirudin when the two agents were given at doses that produced nearly complete inhibition of thrombosis. The more favourable benefit-to-risk profile of melagatran in this model likely reflects better access to fibrin-bound thrombin and the reversible nature of the melagatran/thrombin complex. The theoretical advantages of melagatran may endow it with mechanistic advantages over heparin, and safety advantages over hirudin. Large-scale clinical trials are under way to evaluate the utility of an orally active prodrug form of melagatran for prevention and treatment of venous and arterial thrombosis.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Weitz JIdoi
10.1016/s0049-3848(03)00251-2subject
Has Abstractpub_date
2003-07-15 00:00:00pages
S17-22eissn
0049-3848issn
1879-2472pii
S0049384803002512journal_volume
109 Suppl 1pub_type
杂志文章,评审abstract：:The effect of activated protein C (APC) on agonist-induced platelet activation and on thrombin generation after intrinsic (IA) and extrinsic (EA) activation of the coagulation system was studied by flow cytometry and by measuring levels of prothrombin fragment F1+2. In platelet activation studies blood drawn from heal...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(97)00119-9
更新日期：1997-07-15 00:00:00
abstract：:Antithrombin III (AT III) is increased in situations where there is increased platelet turnover. Plasma AT III levels measured in 39 renal transplant recipients were significantly higher than in 20 healthy subjects (p less than 0.001) and 20 patient controls (p less than 0.025). AT III levels were significantly correl...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(85)90147-1
更新日期：1985-05-01 00:00:00
abstract：:Advances in antithrombotic therapy began when traditional anticoagulant agents such as heparin and the vitamin K antagonists like Coumadin became commercially available in the 1940s and 1950s. Inherent limitations of these compounds, including the need for monitoring and multiple food and drug interactions (with couma...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/j.thromres.2008.08.010
更新日期：2008-01-01 00:00:00
abstract：:It has been suggested that plasma low density lipoprotein (LDL) may affect platelet and leukocyte activity and the release of biologically active eicosanoids which may contribute to the pathogenesis of coronary heart disease. To evaluate the possible biological effects of LDL further we have studied platelet aggregati...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(93)90032-j
更新日期：1993-02-15 00:00:00
abstract：INTRODUCTION:Randomized clinical trials have demonstrated non-inferiority of rivaroxaban compared with vitamin K antagonists (VKAs) in the treatment of venous thromboembolism (VTE). Our objective was to analyze in real life, tolerance, recurrence, bleeding and adverse events of rivaroxaban in patients with acute sympto...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2014.06.032
更新日期：2014-09-01 00:00:00
abstract：INTRODUCTION:Pregnancy has recently been described as a generalized intravascular inflammatory response to the conceptus. Total fibrinogen concentrations increase during pregnancy. The percentage high molecular weight fibrinogen (HMW-Fg) of the concentration total fibrinogen is known to increase during acute-phase cond...
journal_title：Thrombosis research
pub_type： 临床试验,杂志文章
doi：10.1016/j.thromres.2004.04.008
更新日期：2004-01-01 00:00:00
abstract：:The present study has evaluated the effect of some newly synthesized triphenylethylene (TPE) analogs on platelet arachidonic acid metabolism and function. All compounds tested inhibited arachidonic acid induced platelet aggregation and several were superior to aspirin in their relative potency. Introduction of a carbo...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(86)90330-0
更新日期：1986-11-15 00:00:00
abstract：:Intimal proliferation of smooth muscle cells is an important characteristic of developing atherosclerotic lesions and late occlusion of venous bypass grafts. Platelet-derived growth factor, released from aggregating platelets at sites of endothelial injury, has been suggested as a main factor responsible for intimal h...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(89)90042-x
更新日期：1989-04-15 00:00:00
abstract：INTRODUCTION:Venous thromboembolism is a common cause of morbidity and mortality. Although cirrhosis has classically been considered as an acquired bleeding diathesis, there is increasing evidence that rejects the traditional belief that these patients are naturally protected against venous thromboembolism. However, an...
journal_title：Thrombosis research
pub_type： 杂志文章,meta分析,评审
doi：10.1016/j.thromres.2013.08.001
更新日期：2013-10-01 00:00:00
abstract：:Heat treatment is employed to diminish the transmission of hepatitis when blood products are administered. It is possible that such a procedure could reduce the biological activity of the proteins and induce changes in structure and aggregation state. We have therefore made in vitro and pharmacokinetic studies of heat...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(87)90435-x
更新日期：1987-12-15 00:00:00
abstract：:β(2)glycoprotein I (β(2)GPI) is the major antigen in the antiphospholipid syndrome. It has been shown that β(2)GPI can adapt to different conformations, a circular, a S-shaped and a J-shaped conformation. In literature anticoagulant properties of β(2)GPI have been indicated, though there is no consensus on how β(2)GPI...
journal_title：Thrombosis research
pub_type： 杂志文章,评审
doi：10.1016/j.thromres.2012.08.269
更新日期：2012-10-01 00:00:00
abstract：:Lipopolysaccharide-containing outer membrane vesicles (OMV-LPS) which are spontaneously released from Neisseria meningitidis during logarithmic growth were studied for their ability to induce procoagulant (tissue factor), profibrinolytic (urokinase-type plasminogen activator) and antifibrinolytic (plasminogen activato...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(01)00256-0
更新日期：2001-05-15 00:00:00
abstract：INTRODUCTION:Venous thromboembolism (VTE) is a frequent clinical event in patients with gynecologic cancer. However, studies that exclusively address the incidence of VTE according the type of gynecologic cancer are poorly reported. OBJECTIVE:To analyze the incidence of VTE and the associated factors in women with dif...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2019.11.009
更新日期：2020-01-01 00:00:00
abstract：:The release of arachidonic acid, and its subsequent conversion to thromboxane A2, is an important component of platelet activation. The precise mechanism of arachidonic acid release is unknown although cytosolic phospholipase A2 (cPLA2) has been implicated. In the present study the effects of three agonists, the serin...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(98)00097-8
更新日期：1998-10-01 00:00:00
abstract：INTRODUCTION:Normal pregnancy is associated with hypercoagulable state. Elevated markers of coagulation and fibrinolytic system activation indicate increased thrombin activity and increased fibrinolysis following fibrin formation throughout pregnancy. These changes exceed the biological variability in most cases. Haemo...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2013.02.005
更新日期：2013-04-01 00:00:00
abstract：:Sulfation of the natural polysaccharide curdlan results in anticoagulantly active beta-1,3-glucan sulfates whose activity depends on various structural parameters. In this study the anticoagulant and antithrombotic effects of one of these beta-1,3-glucan sulfates (GS) were compared with those of a porcine mucosal hepa...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(95)00049-w
更新日期：1995-05-01 00:00:00
abstract：:The enzymatic activities of uPA, and a collagenase-like proteinase in the post-nuclear fraction of cell homogenates of a metastatic carcinomatous cell line following X-ray irradiation were examined by the use of chromogenic substrates and by casein- or gelatin-containing zymographies and electrophoretic gel stained wi...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(94)90214-3
更新日期：1994-06-15 00:00:00
abstract：PURPOSE:The study sought to synthesize anionic peptide-conjugated tissue plasminogen activator (tPA) for its targeted/triggered delivery, where tPA's activity would be masked in the circulation and regenerated at the thrombus site by a commonly used anticoagulant, heparin, to minimize tPA associated bleeding complicati...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2012.11.030
更新日期：2013-03-01 00:00:00
abstract：:Megakaryocyte colony formation was increased in 13 patients with ITP. Out of splenectomized ITP patients Colony Forming Unit-Megakaryocyte (CFU-Mk) number normalized in four but was lower than normal in the remaining two. The proportion of immature megakaryocytes was higher in ITP than in normals or in ITP patients af...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(91)90672-j
更新日期：1991-04-01 00:00:00
abstract：:We determined the extent and duration of activation of coagulation during the first 24 hours after carotid endarterectomy. Serial blood samples were collected before, during and after surgery from 10 patients with severe stenosis (> 70%) undergoing carotid endarterectomy with heparinization. Platelet poor plasmas prep...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(94)90257-7
更新日期：1994-08-15 00:00:00
abstract：:We investigated the relationship between the procoagulant protease-inhibitory activity and the N-glycan structures in urinary protein C inhibitor (uPCI) by sequential exoglycosidase digestions based on the N-glycan structures elucidated in this report. uPCI was glycosylated on the three potential N-glycosylation sites...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/s0049-3848(01)00342-5
更新日期：2001-10-01 00:00:00
abstract：:Time response curves of the anti-thrombotic effects, bleeding enhancing effects, effects on APTT, anti-Xa activities, anti-thrombin activities and thrombin generation inhibitory activities of the low molecular weight heparinoid Org 10172 and heparin have been compared in rats. The time courses of these effects were si...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(87)90386-0
更新日期：1987-12-01 00:00:00
abstract：INTRODUCTION:Pseudoprolongation of activated partial thromboplastin time (APTT) is a serious problem in anticoagulation therapy for patients with high hematocrit, such as cyanotic congenital heart diseases. APTT pseudoprolongation occurs when APTT assay is performed using routinely used vacuum sampling tubes containing...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2007.08.004
更新日期：2008-01-01 00:00:00
abstract：BACKGROUND:The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS). OBJECTIVE:We aimed to evaluate the level of PR inhibition ac...
journal_title：Thrombosis research
pub_type： 杂志文章,多中心研究
doi：10.1016/j.thromres.2013.04.030
更新日期：2013-07-01 00:00:00
abstract：:VKORC1 and VKORC1L1 are enzymes that both catalyze the reduction of vitamin K2,3-epoxide via vitamin K quinone to vitamin K hydroquinone. VKORC1 is the key enzyme of the classical vitamin K cycle by which vitamin K-dependent (VKD) proteins are γ-carboxylated by the hepatic γ-glutamyl carboxylase (GGCX). In contrast, t...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2015.01.025
更新日期：2015-05-01 00:00:00
abstract：INTRODUCTION:Pulmonary embolism (PE) has a high morbidity and mortality. Hence it is important to recognize factors associated with higher risk of adverse outcomes in hemodynamically stable patients. Heart-type fatty acid binding protein (H-FABP) is a novel marker evaluated in recent years for prognosis in acute PE. Ou...
journal_title：Thrombosis research
pub_type： 杂志文章,meta分析
doi：10.1016/j.thromres.2014.10.007
更新日期：2015-01-01 00:00:00
abstract：:The effect of warfarin-induced factor VII deficiency on the skin bleeding time was investigated in 10 consecutive patients with mean prothrombin times of 33 sec and factor VII levels of 7%. Bleeding times in all but one subject were entirely within the normal range. We conclude that warfarin administration, even to th...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(83)90243-8
更新日期：1983-02-15 00:00:00
abstract：:In rabbits, a clear microscopic image of individual, fluorescent blood platelets flowing in a mesenteric microvessel could be obtained over the whole cross-sectional area of the vessel, following an intravenous injection of a solution containing 5-15 mg of the fluorochrome Acridine Red. Most of the circulating platele...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(82)90106-2
更新日期：1982-12-15 00:00:00
abstract：:Algal fucoidans possess a wide variety of biological activities, including anticoagulation and antithrombosis, making them potential candidates for clinical use. We assessed the antiaggregant, anticoagulant and antithrombotic activities and the underlying mechanism of the low- and high-molecular weight fucoidans from ...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2010.02.011
更新日期：2010-05-01 00:00:00
abstract：INTRODUCTION:The A-subunit of blood coagulation factor XIII is a pro-transglutaminase, which cross-links α- and γ-fibrin-chains in its activated form. Selective inhibitors against FXIII-A may be desirable drugs to prevent the development of thromboses. Animal models are generally used for proof of principle and for tox...
journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2013.02.008
更新日期：2013-05-01 00:00:00
