| Blood coagulation dynamics in haemostasis. | |
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MedLine Citation:
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PMID: 19151839 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Our studies involve computational simulations, a reconstructed plasma/platelet proteome, whole blood in vitro and blood exuding from microvascular wounds. All studies indicate that in normal haemostasis, the binding of tissue factor (TF) with plasma factor (F) VIIa (extrinsic FXase complex) results in the initiation phase of the procoagulant response. This phase is negatively regulated by tissue factor pathway inhibitor (TFPI) in combination with antithrombin (AT) and the protein C (PC) pathway. The synergy between these inhibitors provides a threshold-limited reaction in which a stimulus of sufficient magnitude must be provided for continuation of the reaction. With sufficient stimulus, the FXa produced activates some prothrombin. This initial thrombin activates the procofactors and platelets required for presentation of the intrinsic FXase (FVIIIa-FIXa) and prothrombinase (FVa-FXa) complexes which drive the subsequent propagation phase; continuous downregulation of which is provided by AT and the thrombin-thrombomodulin-PC complex. FXa generation during the propagation phase is largely (>90%) provided by the intrinsic FXase complex. TF is required for the initiation phase of the reaction but becomes non-essential once the propagation phase has been achieved. The propagation phase catalysts (FVIIIa-FIXa and FVa-FXa) continue to drive the reaction as blood is resupplied to the wound site by flow. Ultimately, the control of the reaction is governed by the pro- and anticoagulant dynamics and the supply of blood reactants to the site of a perforating injury. Our systems have been utilized to examine the qualities of hypothetical and novel antihaemorrhagic and anticoagulation agents and in epidemiologic studies of venous and arterial thrombosis and haemorrhagic pathology. |
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Authors:
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K G Mann; T Orfeo; S Butenas; A Undas; K Brummel-Ziedins |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Hämostaseologie Volume: 29 ISSN: 0720-9355 ISO Abbreviation: Hamostaseologie Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-19 Completed Date: 2009-03-24 Revised Date: 2011-08-25 |
Medline Journal Info:
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Nlm Unique ID: 8204531 Medline TA: Hamostaseologie Country: Germany |
Other Details:
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Languages: eng Pagination: 7-16 Citation Subset: IM |
Affiliation:
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University of Vermont, Department of Biochemistry, Burlington, VT, USA. Kenneth.Mann@uvm.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Blood Coagulation
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physiology* Blood Coagulation Factors / metabolism Blood Proteins / metabolism Fibrinogen / metabolism Hemostasis / physiology* Humans Kinetics Models, Biological Proteome Thrombin / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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P01 HL046703-16A1/HL/NHLBI NIH HHS; P01 HL046703-17/HL/NHLBI NIH HHS; P01 HL46703/HL/NHLBI NIH HHS; R01 HL034575-20/HL/NHLBI NIH HHS; R01 HL034575-21/HL/NHLBI NIH HHS; R01 HL34575/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Blood Coagulation Factors; 0/Blood Proteins; 0/Proteome; 9001-32-5/Fibrinogen; EC 3.4.21.5/Thrombin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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