Abstract：
:Edoxaban is an oral direct factor (F)Xa inhibitor in advanced stages of clinical development. The primary objective of the present study was to assess the pharmacodynamics (PD) and safety of enoxaparin 1 mg/kg followed 12 hours (h) post-dose by edoxaban 60 mg, which is the regimen being used in the phase III study of edoxaban for the treatment of venous thromboembolism (Hokusai-VTE). This was a phase I, open-label, randomised, four-period, four-treatment cross-over study. Treatments were edoxaban alone (EDOX), enoxaparin alone (ENOX), edoxaban plus enoxaparin (EDOX+ENOX), and enoxaparin followed by edoxaban 12 h later (ENOX12-EDOX). Serial blood samples were collected for PD (thrombin generation, anti-FXa) and pharmacokinetic (PK) variables (edoxaban and its principal metabolite M4 by LC-MS/MS, and anti-FIIa as a surrogate of enoxaparin). The highest effect on thrombin AUC (endogenous thrombin potential, or ETP), thrombin (peak), thrombin generation lag time, and velocity index was observed for EDOX+ENOX, followed by ENOX, ENOX12-EDOX, and EDOX. The greatest effect on anti-FXa activity was observed for EDOX+ENOX, followed by ENOX12-EDOX. As expected, neither edoxaban nor enoxaparin significantly altered the PK of the other drug. There were no serious adverse events during the study. It is concluded that a 60-mg dose of edoxaban can be safely administered 12 h following enoxaparin 1 mg/kg.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Zahir H,Matsushima N,Halim AB,He L,Zhang G,Lee F,Worland V,Mendell Jdoi
10.1160/TH11-09-0676subject
Has Abstractpub_date
2012-07-01 00:00:00pages
166-75issue
1eissn
0340-6245issn
2567-689Xpii
11-09-0676journal_volume
108pub_type
杂志文章,随机对照试验abstract：:In the last decade, the endothelial cell protein C/activated protein C receptor (EPCR) has received considerable attention. The role initially attributed to EPCR, i.e. the enhancement of protein C (PC) activation by the thrombin-thrombomodulin complex on the surface of the large vessels, although important, did not go...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH11-11-0766
更新日期：2012-05-01 00:00:00
abstract：:In the past decade understanding of the role of the Rho GTPases RhoA, Rac1 and Cdc42 has been developed from regulatory proteins that regulate specific actin cytoskeletal structures - stress fibers, lamellipodia and filopodia - to complex integrators of cytoskeletal structures that can exert multiple functions dependi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH09-06-0403
更新日期：2010-01-01 00:00:00
abstract：:The efficiency of current dual antiplatelet therapy might be further improved by its combination with a glycoprotein (GP) VI-targeting strategy without increasing bleeding. GPVI-Fc, a recombinant dimeric fusion protein binding to plaque collagen and concealing binding sites for platelet GPVI, acts as a lesion-focused ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH16-11-0856
更新日期：2017-08-01 00:00:00
abstract：:We studied human platelet aggregation and beta-TG/PF4 release induced by heparin and related GAGs in vitro both in normal PRP and in PRP after aspirin. In our experimental conditions, heparin and related GAGs always caused PF4 release in vitro from normal platelets, whether or not there was measurable platelet aggrega...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1984-02-28 00:00:00
abstract：:To study the reversible complex formation between the plasma protein histidine-rich glycoprotein (HRG) and plasminogen, crossed immunoelectrophoresis of HRG was modified. In the modification, purified plasminogen was introduced into the gel of the first dimension electrophoresis. Two molecular forms of plasminogen, Gl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1988-12-22 00:00:00
abstract：:Measurement of heparin ex vivo is usually with reference to standard curve prepared with a "spiked" normal human plasma pool (NHP). When the calibration curve was prepared by addition of heparin to whole blood before plasma separation, although the linear relationship was maintained the slope was increased in comparis...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1989-04-25 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：:Nipah virus (NiV) is a highly pathogenic paramyxovirus that was first isolated in 1999 during an outbreak in Malaysia. In contrast to other paramyxoviruses NiV infects many mammalian species. Because of its zoonotic potential, the high pathogenicity and the lack of therapeutic treatment, NiV was classified as a biosaf...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH09-05-0310
更新日期：2009-12-01 00:00:00
abstract：:Seven mouse monoclonal antibodies have been produced against human melanoma tissue plasminogen activator (t-PA). They were specifically bound to 125I t-PA but not 125I urokinase (u-PA) and inhibited t-PA, but not u-PA, activity in plasminogen-rich 125I fibrin wells. Three of the antibodies directly inhibited the amido...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-02-18 00:00:00
abstract：:Heparin therapy was monitored with the activated partial thromboplastin time (APTT) and with chromogenic substrate assays (factor Xa and factor IIa inhibition) in 100 plasma samples from 47 patients. Heparin concentrations were classified as being below, within or above a defined therapeutic range (TR; 0.2-0.55 units ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1987-10-28 00:00:00
abstract：:Tissue factor (TF) plays a pivotal role in thrombus formation and atherogenesis in acute coronary syndrome. Tissue factor pathway inhibitor (TFPI) is a specific physiological inhibitor of TF/FVIIa complex that regulates TF-induced coagulation. Adiponectin (Adp) is an adipocyte-specific adipocytokine with anti-atheroge...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2008-08-01 00:00:00
abstract：:Catheter-directed thrombolysis has gained increasing acceptance for the treatment of patients who present with vascular occlusion; however, intravenous injection may be preferable in selected patients. Recombinant prourokinase (r-proUK) is a recently-developed fibrin-selective thrombolytic agent with specificity for c...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
abstract：:Fibrinogen degradation products were investigated for leukocyte chemotactic activity and for enhancement of vascular permeability. Both activities increased progressively with plasmin digestion of fibrinogen. Active fragments were partially purified from 24 hr-plasmin digests. Molecular weights of the permeability inc...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1981-02-23 00:00:00
abstract：:Thrombus formation is recognized pathologically in the affected arteries and is supposed to play a major role in the pathogenesis of Takayasu's arteritis; however, hemostatic conditions in this disorder have not been elucidated fully. We determined plasma levels of molecular markers for platelet activity (platelet fac...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-05-01 00:00:00
abstract：:It has previously been reported that EGF enhances uPA but not tPA in the A431 squamous carcinoma cell line. To determine whether the absence of tPA modulation by EGF reflected steady levels or the action of an anti-activator, we assayed tPA, PAI-1 and tPA/PAI-1 complexes by zymography and immunological assays. Under c...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-11-30 00:00:00
abstract：:This study assessed the abundance and activity of thrombin in human thrombi. removed at autopsy or during surgery. Arterial and venous thrombus sections showed thrombin activity by in situ zymography, based on conversion of fibrinogen to fibrin. Hirudin or antibodies to thrombin abolished the activity. Thrombin activi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:To evaluate the safety of a beta-Propiolactone/Ultraviolet (BPL/UV), irradiated Factor IX complex preparation we inoculated 8 chimpanzees with 25 units Factor IX/Kilo from a pool of 5 production lots which had been treated in this manner. These lots were derived from approximately 1,000 donors. Animals were followed w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-12-19 00:00:00
abstract：:The recombinant plasminogen activator BM 06.022 consists of the kringle 2 and the protease domains of human t-PA and is unglycosylated because of the expression in Escherichia coli. The thrombolytic and pharmacokinetic properties as well as the hemostasis effects of BM 06.022 were investigated in the rabbit model of j...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1991-05-06 00:00:00
abstract：:Serine proteases are proteolytic enzymes with an active serine residue in their catalytic site. Kallikreins are a subgroup of the serine protease family and are known to have diverse physiological functions. The human tissue kallikrein gene family has now been fully characterized and includes 15 members, clustered in ...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：
更新日期：2003-07-01 00:00:00
abstract：:The structures of bovine and human vWF were compared by proteolysis with Staphylococcus aureus V8 protease and rattlesnake venom Protease I. Fragments were analyzed for chain composition, heparin binding, collagen binding, platelet agglutinating activity and recognition by a panel of monoclonal antibodies which reacte...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-06-28 00:00:00
abstract：:Endothelial cell protein C receptor (EPCR) enhances the generation of activated protein C (APC) by the thrombin-thrombomodulin complex. A soluble form of EPCR (sEPCR), which is generated by metalloprotease activity, is present in plasma. The distribution of sEPCR levels in healthy populations is bimodal. Previously, w...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH03-10-0657
更新日期：2004-05-01 00:00:00
abstract：:1. Some of the guidelines on the nomenclature for the genotype of bacterial strains can be applied for recommendations on the nomenclature for the description of recombinant mutant fibrinolytic constructs. 2. In view of the usually different size of genomic DNA and corresponding cDNA, it is recommended to employ a dis...
journal_title：Thrombosis and haemostasis
pub_type： 指南,杂志文章
doi：
更新日期：1990-12-28 00:00:00
abstract：:Leukocytes recruitment to thrombi supports an intimate cellular interaction leading to the enhancement of pro-coagulant functions and pro-inflammatory responses at site of vascular injury. Recent observations of neutrophil extracellular traps (NETs) formation and its mutual reactions with platelet thrombi adds more cl...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章,评审
doi：10.1160/TH14-08-0662
更新日期：2015-06-01 00:00:00
abstract：:Heparin cofactor II (HC II) is a heparin-dependent inhibitor of thrombin, distinct from antithrombin III (AT III). This study was designed to evaluate its metabolism in healthy subjects. Purified HC II was labelled with 125I by the lactoperoxidase-glucose oxidase technique. The biological activity of the HC II was unc...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1985-10-30 00:00:00
abstract：:We have previously shown that both mental stress and administration of the muscarinic receptor agonist methacholine induce an acute release of tissue-type plasminogen activator (t-PA) across the human forearm. There are data indicating that the regulated acute release of t-PA from the endothelium is closely interrelat...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1997-08-01 00:00:00
abstract：:High heparin cofactor II (HCII) activity has recently been described to protect from coronary instent restenosis, presumably by inactivating thrombin in injured arteries. In this study, we investigated the association of HCII activity and restenosis after femoropopliteal stenting. We studied 63 consecutive patients wi...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH04-05-0311
更新日期：2004-11-01 00:00:00
abstract：:Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG). We sought to determine the diagnostic validity of plasma biomarkers of i) inflammation (marked by interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]), ii) extracellular matrix remodelling (matrix metalloprot...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：10.1160/TH09-12-0837
更新日期：2010-07-01 00:00:00
abstract：:Amniotic fluid inhibited the fibrinolytic, amidolytic and esterolytic activity of urokinase. Kinetic studies with AGLMe demonstrated non-competitive inhibition. A major part of the inhibitory activity could be separated from alpha 1-antitrypsin by ion-exchange chromatography on DEAE-Sephadex A-50. Plasminogen activato...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1980-08-29 00:00:00
abstract：:The vitamin K-dependent carboxylation of specific glutamyl residues to gamma-carboxyglutamyl residues occurs during the endoplasmic reticulum processing of a limited number of proteins. The fate of the under-gamma-carboxylated proteins during protein processing was studied. When human hepatoma (HepG2) cells were grown...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:The generation of D-dimer was studied in the course of local thrombolytic therapy of peripheral arterial occlusions with low doses of recombinant human tissue-type plasminogen activator (rt-PA) in 7 patients. Intermittent local application of rt-PA resulted in a marked increase in D-dimer exceeding values usually seen...
journal_title：Thrombosis and haemostasis
pub_type： 杂志文章
doi：
更新日期：1990-10-22 00:00:00
