2005 Fiscal Year Final Research Report Summary
Clarification of mechanisms for thrombus formation under physiologic blood flow
| Project/Area Number |
15390305
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Nara Medical University |
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Principal Investigator |
SUGIMOTO Mitsuhiko Nara Medical Univ., Facult. Med., Lecturer, 医学部, 講師 (80192128)
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| Co-Investigator(Kenkyū-buntansha) |
NOGAMI Keiji Nara Medical Univ., Facult. Med., Assistant, 医学部, 助手 (50326328)
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| Project Period (FY) |
2003 – 2005
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| Keywords | platelet thrombus formation / blood coagulation / physiologic blood flow / flow chamber / confocal microscopy |
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| Research Abstract |
Mural thrombus formation at sites of damaged vessel wall, essential for both physiologic hemostasis and pathologic intravascular thrombosis, is established by the concerted function of platelet aggregation and fibrin clot formation. However, most of previous in vitro coagulation assays evaluated fibrin clot formation in a static or closed stirring situation that lacked blood cells including platelets, We have therefore modified a flow chamber system originally established for platelet functional studies, thereby observing the real-time process of intra-thrombus fibrin deposition during platelet thrombus growth under flow conditions. The analysis by confocal laser scanning microscopy in perfusion of whole blood that were anticoagulated to various extents revealed that the development of intra-thrombus fibrin deposition significantly affected the size and shape of individual mural thrombi generated under high shear rate conditions. These observations, reflecting the in vivo comprehensive thrombogeneicity, were further confirmed when heparinized whole blood or whole blood from severe hemophilic patients with or without addition of activated factor VII was perfused. Thus, our experimental approach could help extend understandings for pathogenesis of congenital coagulation disorders as well as for the action mechanisms of various anticoagulants targeting thrombotic diseases, representing the "cell-based coagulation under whole blood flow" that could be most relevant for in vivo hemostasis and thrombosis.
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