Abstract:
:DX-9065a is an antithrombin III (AT III)-independent and selective inhibitor of activated blood coagulation factor X (FXa). We evaluated the effects of DX-9065a and warfarin on bleeding time and blood loss in rat tail transection model and on blood loss in hydrochloride (HCl)-induced rat gastrointestinal haemorrhage model. The blood loss was determined by measuring the haemoglobin content in saline immersed with transected tail or hematin chloride content in the gaster after HCl administration. DX-9065a or warfarin was administered orally at 1 h or 15-21 h before the haemorrhagic stimuli, respectively. The dose required for 50% inhibition of thrombus formation (ID50) was 21 mg/kg for DX-9065a and 0.75 mg/kg for warfarin in a copper wire-inserted arteriovenous (AV) shunt model. In contrast to DX-9065a (10 or 30 mg/kg), warfarin (0.75 mg/kg) significantly prolonged the bleeding time. In rat tail transection model, the blood loss for the control group was 102+/-41 microl at 20 min after the transection. While warfarin (0.75 mg/kg) facilitated the blood loss about 5 times as much as the control, DX-9065a (10 or 30 mg/kg) did not. In rat gastrointestinal model, the blood loss for the control group was 15.9+/-5.6 microl at 15 min after HCl administration. In contrast to DX-9065a (10 or 30 mg/kg), warfarin (0.75 mg/kg) increased the blood loss about twice as much as the control. Thus, compared with warfarin, DX-9065a only increased bleeding time or blood loss to a minor extent in the doses tested. These observations suggest that direct inhibition of FXa could be preferable to warfarin in the suppression of thrombosis without haemorrhagic complications.
journal_name
Thromb Haemostjournal_title
Thrombosis and haemostasisauthors
Tanabe K,Morishima Y,Shibutani T,Terada Y,Hara T,Shinohara Y,Aoyagi K,Kunitada S,Kondo Tkeywords:
subject
Has Abstractpub_date
1999-05-01 00:00:00pages
828-34issue
5eissn
0340-6245issn
2567-689Xpii
99050828journal_volume
81pub_type
杂志文章abstract::A new immunoadsorbent-amidolytic assay (IAA) for the specific differential detection of two-chain urokinase-type plasminogen activator (tcu-PA) and its single-chain precursor (scu-PA) in cell culture supernatants has been developed. The assay combines the selectivity of immunoassays with the specificity of enzyme acti...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-12-15 00:00:00
abstract::We have previously shown that human platelets express matrix metalloproteinase-2 (MMP-2) and that the release of this enzyme during platelet activation mediates the ADP- and thromboxane-independent part of aggregation. We have now used immunogold electron microscopy, flow cytometry. Western blot analysis and zymograph...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-11-01 00:00:00
abstract::The novel fast inhibitor to tissue plasminogen activator in plasma has been determined in 20 healthy non-pregnant women, 48 apparently healthy pregnant women and 136 women with risk pregnancies (preeclampsia, suspected fetal growth retardation, thrombosis or previous history of thrombosis, diabetes and others). In hea...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1984-10-31 00:00:00
abstract::Collagen (10-90 micrograms/ml) and ionomycin (1 microM; a calcium ionophore) each evoked rises in intracellular free calcium, protein kinase C activity and arachidonic acid release in human platelets, and as previously demonstrated for collagen, ionomycin (1 microM) stimulated protein tyrosine phosphorylation. However...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::The Ig-ITIM superfamily member, PECAM-1 acts as a negative regulator of ITAM-signalling pathways in platelets involving GPVI/FcR gamma chain and Fc?RIIa. This negative feedback loop involves regulation of collagen and GPVI-dependent aggregation events, platelet-thrombus-growth on immobilised collagen under flow and Fc...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2006-12-01 00:00:00
abstract::Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is mainly caused by dominant-negative mutations in the multimeric protein von Willebrand factor (VWF). These mutations may either result in quantitative or qualitative defects in VWF. VWF is an endothelial protein that is secreted to the c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1715442
更新日期:2020-11-01 00:00:00
abstract::Heparin and low molecular weight heparins stimulate two to three fold the accumulation of an antithrombotic heparan sulfate secreted by endothelial cells in culture. This led us to search for the minimum structural requirements of the heparin molecule able to elicit the enhancement of the heparan sulfate. Fragments we...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::In this study we sought to evaluate if platelet function measured after percutaneous coronary intervention (PCI) affects the severity of myocardial infarction (MI), measured by markers of cardiac necrosis. We measured platelet function by both a point-of-care assay (PFA-100) and platelet-rich plasma aggregation by two...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2007-10-01 00:00:00
abstract::Platelets from a patient with an acquired hemorrhagic disorder had a severely impaired response to collagen, whereas platelet aggregation to other agonists and coagulations tests were normal. No abnormalities of the patient's platelet membrane glycoproteins (GP) were seen. Treatment of the patient with immunosuppressi...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1990-08-13 00:00:00
abstract::Primary immune thrombocytopaenia (ITP) is the most common haemorrhagic disease. Although most patients respond initially to mainstream therapies, such as corticosteroids, immunosuppressants or rituximab, a large proportion of patients fail to respond or relapse. These treatments only affect B lymphocytes or short-live...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1055/s-0038-1669921
更新日期:2018-10-01 00:00:00
abstract::Restenosis following successful percutaneous coronary revascularization continues to represent a major problem limiting the clinical efficacy of this procedure. The underlying mechanisms of restenosis are comprised of a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-09-01 00:00:00
abstract::Hematological parameters including platelet counts, etc. were determined in 1,140 healthy subjects living in four cities: Suzhou (Jiangsu Province), Chengdu (Sichuan Province) and Harbin (Heilongjang Province) in China, and Kobe in Japan. Then, the reference intervals for platelet counts were calculated and compared. ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
abstract::In the last decade, several studies revealed inter-patient response variability to antiplatelet agents: patients who display negligible or no responses to these drugs are considered poor responders, or "resistant" to treatment. In order to identify poor responders to an antiplatelet drug, laboratory tests of platelet ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH12-10-0758
更新日期:2013-05-01 00:00:00
abstract::Molsidomine and its active metabolite SIN-1 were examined in humans and animals for platelet suppressant and fibrinolytic activities. Following oral administration of molsidomine at doses of 6 or 15 mg/kg to rabbits, their blood platelets in PRP ex vivo required higher threshold concentrations of ADP, AA and thrombin ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1985-12-17 00:00:00
abstract::The measurement of platelet deposition in human thrombi is essential for the evaluation of platelet-inhibitory drugs and prosthetic materials for use in patients. The rate of 111Indium-labelled platelet accumulation on Dacron arterial grafts was measured in 27 patients randomised to take either aspirin and dipyridamol...
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:1982-12-27 00:00:00
abstract::Since megakaryocytes are the cellular precursors of platelets we have investigated whether they share responses to platelet agonists, in particular collagen. Although previous studies have reported responses to thrombin in non-human megakaryocytes, through studies of single cell calcium responses and protein tyrosine-...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-09-01 00:00:00
abstract::Isolated rat hepatocytes possess per cell 4,500 high-affinity binding sites for thrombin with a Kd of 30-40 pM, and 2.8 X 10(5) low-affinity sites with a Kd of 30 nM. These binding sites are highly specific for thrombin. Half-maximal binding of 125I-labelled thrombin is achieved after 3 min at 37 degrees C and 7 min a...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1988-12-22 00:00:00
abstract::Vascular injury in acute coronary syndromes (ACS) involves a complex cross-talk between inflammatory mediators, platelets and thrombosis, where the interaction between platelets and coagulation factors (e. g. thrombin) is a central link between thrombosis and inflammation. In ACS, aspirin at antiplatelet doses exhibit...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,评审
doi:10.1160/TH15-03-0191
更新日期:2015-08-31 00:00:00
abstract:BACKGROUND: Anticoagulant therapy has seldom been achieved in randomized trials targeting nonspecific overall sepsis patients. Although the key components to identify the appropriate target in sepsis may be disseminated intravascular coagulation (DIC) and high disease severity, the interaction and relation of these two...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1055/s-0039-1693740
更新日期:2019-11-01 00:00:00
abstract::Anticoagulant control facilities are being overwhelmed by requests for monitoring and large numbers of patients are not therefore receiving treatment. Procedures designed for point-of-care testing have therefore been developed, the most popular being the CoaguChek. The need for external quality assessment (EQA) of mon...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章,多中心研究
doi:10.1160/TH09-10-0683
更新日期:2010-05-01 00:00:00
abstract::Deep-vein thrombosis (DVT) is a common condition that often leads to pulmonary thromboembolism (VTE) and death. The role of prostaglandin-endoperoxide synthase (PTGS)2 in arterial thrombosis has been well established, whereas its impact in venous thrombosis remains unclear. Here, we showed that PTGS2 deletion predispo...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH16-12-0968
更新日期:2017-07-26 00:00:00
abstract::A congenitally abnormal fibrinogen was isolated from blood of a young man with deep-vein thrombosis. Two other affected members of his family had three episodes of severe arterial thrombosis. The fibrinogen showed a delayed clotting by thrombin, but a normal clotting by Arvin, Reptilase, and prothrombin-staphylocoagul...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1986-02-28 00:00:00
abstract::A double antibody competition radioimmunoassay was developed that allowed to detect specifically as little as 15 ng antithrombin III (AT III) per ml of the assayed material. In normal plasma examined by this assay, AT III concentration averaged 199 +/- 21 micrograms/ml. Complexes of AT III with thrombin or factor Xa c...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1983-02-28 00:00:00
abstract::In this study, the clot accumulation properties of liposome-coupled plasminogen were compared to those of free (non-liposomal) plasminogen in an in vitro, closed-loop, flow-system. After introduction of a clot into the closed system, double-radiolabelled plasminogen-liposomes were administered and the accumulation of ...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract::Inherited thrombophilic states are associated with an increased risk for deep vein thrombosis (DVT), but whether they are also risk factors for superficial vein thrombosis (SVT) is uncertain. We assessed the risk conferred by inherited thrombophilic states in patients with a first episode of SVT in whom the coexistenc...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1999-10-01 00:00:00
abstract::Human high molecular weight kininogen (HK), a single chain plasma glycoprotein, serves as a cofactor in the contact system of blood coagulation. After cleavage by human plasma kallikrein, the nonapeptide bradykinin is released. The HK light chain (LC) contains coagulant activity, which requires both the ability to bin...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1992-04-02 00:00:00
abstract::Probands from 15 unrelated families with hereditary protein S deficiency type I, that is having a plasma total protein S concentration fifty percent of normal, were screened for abnormalities in their protein S genes by Southern analysis. Two probands were found to have a deviating DNA pattern with the restriction enz...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-11-24 00:00:00
abstract::Previous studies have demonstrated that cell-permeable cytoplasmic tail (CT) alpha(II)beta peptides can modulate the activation of alpha(IIb)b(3). As alpha(V) CT contains an alpha(II)beta homologous region, a series of cell-permeable alpha(V) and alpha(IIb) peptides were generated to determine if alpha(V) CT can modul...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH07-08-0498
更新日期:2008-01-01 00:00:00
abstract::Coronary artery disease (CAD) is a multifactorial disease, and family history is the best available tool to assess gene-environment interaction. This study addressed the heritability of quantitative traits, namely lipid, coagulation/fibrinolysis and pro-inflammatory markers in the ongoing family-based Indian Atheroscl...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:10.1160/TH08-01-0018
更新日期:2009-08-01 00:00:00
abstract::This article describes the results of a dietary intervention study performed in three different centers. In the study the effect of a diet enriched with fish on the coagulation tendency of blood was investigated. Two groups of 40 volunteers were given a dietary supplement consisting of 135 g of canned mackerel or meat...
journal_title:Thrombosis and haemostasis
pub_type: 杂志文章
doi:
更新日期:1989-06-30 00:00:00