| Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats. | |
| | |
MedLine Citation:
|
PMID: 20452654 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
INTRODUCTION: Activated platelets facilitate blood coagulation by providing factor V and a procoagulant surface for prothrombinase. Here, we investigated the potential synergy of a potent factor Xa/prothrombinase inhibitor, TAK-442, plus aspirin or clopidogrel in preventing arterial thrombosis and whole blood coagulation. METHODS: Thrombus formation was initiated by FeCl(3)-induced rat carotid injury. Bleeding time was evaluated with the rat tail transection model. Whole blood coagulation was assessed by thromboelastographic examination (TEG) for which blood obtained from control, aspirin-, or clopidogrel-treated rats was transferred to a TEG analyzer containing, collagen or adenosine diphosphate (ADP), and TAK-442 or vehicle. RESULTS: TAK-442 (3mg/kg, po), aspirin (100mg/kg, po) or clopidogrel (3mg/kg, po) alone had no significant effect on thrombus formation, whereas the combination of TAK-442 with aspirin and clopidogrel remarkably prolonged the time to thrombus formation without additional significant prolongation of bleeding time. TEG demonstrated that the onset of collagen-induced blood coagulation were slightly longer in aspirin-treated rats than control; however, when the blood from aspirin-treated rats was subsequently treated in vitro with 100 nM TAK-442, the onset of clotting was significantly prolonged. In contrast, only marginal prolongation was observed with TAK-442 treatment of blood from control animals. The onset time of ADP-induced blood coagulation was slightly longer in clopidogrel-treated rats compared with control, and it was further extended by TAK-442 treatment. CONCLUSION: These results demonstrate that blood coagulation can be markedly delayed by the addition of TAK-442 to antiplatelets treatment which could contribute to synergistic antithrombotic efficacy in these settings. |
| | |
Authors:
|
Noriko Konishi; Katsuhiko Hiroe; Masaki Kawamura |
Related Documents
:
|
1779914 - Cytokines. a unifying concept in the pathogenesis of clubbing. 9684084 - Review and consideration of coagulopathies. 9702614 - Differential effects of serial hemodilution with hydroxyethyl starch, albumin, and 0.9%... 17405864 - Extracellular rna constitutes a natural procoagulant cofactor in blood coagulation. 1867114 - Examination of microvascular structures of midcortical region in sheep kidneys: a three... 2191674 - Blood flow: insights from ultrasound. |
Publication Detail:
|
Type: Journal Article Date: 2010-05-10 |
Journal Detail:
|
Title: Thrombosis research Volume: 126 ISSN: 1879-2472 ISO Abbreviation: Thromb. Res. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-07-27 Completed Date: 2010-11-29 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0326377 Medline TA: Thromb Res Country: United States |
Other Details:
|
Languages: eng Pagination: 124-9 Citation Subset: IM |
Copyright Information:
|
(c) 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
|
Pharmacology Research Laboratories, Takeda Pharmaceutical Company Ltd., Osaka, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Aspirin / pharmacology, therapeutic use* Blood Coagulation / drug effects* Blood Coagulation Tests Drug Synergism Factor Xa / antagonists & inhibitors* Male Platelet Aggregation / drug effects Platelet Aggregation Inhibitors / pharmacology, therapeutic use* Pyrimidinones / pharmacology, therapeutic use* Rats Rats, Sprague-Dawley Sulfones / pharmacology, therapeutic use* Thrombosis / drug therapy* Ticlopidine / analogs & derivatives*, pharmacology, therapeutic use |
| Chemical | |
Reg. No./Substance:
|
0/1-(1-(3-((6-chloronaphthalen-2-yl)sulfonyl)-2-hydroxypropanoyl)piperidin-4-yl)tetrahydropyrimidin-2(1H)-one; 0/Platelet Aggregation Inhibitors; 0/Pyrimidinones; 0/Sulfones; 50-78-2/Aspirin; 55142-85-3/Ticlopidine; 90055-48-4/clopidogrel; EC 3.4.21.6/Factor Xa |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Frequency and hemostatic abnormalities in pre-DIC patients.
Next Document: The Cone-and-Plate(let) analyzer is not suitable to monitor clopidogrel therapy: A comparison with t...