Document Detail


Antithrombotic effect of a monoclonal antibody against tissue factor in a rabbit model of platelet-mediated arterial thrombosis.
MedLine Citation:
PMID:  1637793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of the coagulation system by contact of circulating blood with tissue factor, a component of the extrinsic blood coagulation pathway that is produced in the vessel wall, may represent a pathway for the initiation of thrombosis in atherosclerotic vessels. This hypothesis was tested in vivo in a rabbit femoral artery eversion (inside-out) graft model, in which the adventitia, with its tissue factor, was exposed to circulating blood. Intra-arterial infusion of a neutralizing monoclonal antibody against tissue factor (D3) at a rate of 12 mg/kg over 15 minutes prevented thrombosis of a 7-8-mm eversion graft within a 2-hour observation period in four of five rabbits, whereas with a control antibody infusion (MA-15C5), occlusion occurred within 2 hours in five of six rabbits. In vitro immersion before reinsertion of the arterial segment in a solution containing 2 mg/ml of the control antibody for 30 minutes was associated with occlusion in all six rabbits, whereas pretreatment with D3 was associated with persistent patency in three of nine rabbits. Stepwise logistic-regression analysis of the results with perfusion status as the dependent variable and type of antibody (D3 or MA-15C5), application method (infusion versus immersion), and graft segment length as independent variables yielded a significant difference in frequency of occlusion with the two antibodies (p = 0.016). It is concluded that exposure of tissue factor to flowing blood may constitute a trigger mechanism for platelet-mediated arterial thrombosis.
Authors:
I K Jang; H K Gold; R C Leinbach; J T Fallon; D Collen; J N Wilcox
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association     Volume:  12     ISSN:  1049-8834     ISO Abbreviation:  Arterioscler. Thromb.     Publication Date:  1992 Aug 
Date Detail:
Created Date:  1992-09-01     Completed Date:  1992-09-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9101388     Medline TA:  Arterioscler Thromb     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  948-54     Citation Subset:  IM    
Affiliation:
Cardiac Unit, Massachusetts General Hospital, Boston 02114.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / therapeutic use*
Blood Platelets / physiology*
Rabbits
Thromboplastin / immunology,  physiology*
Thrombosis / etiology,  pathology,  therapy*
Grant Support
ID/Acronym/Agency:
HL-26205/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 9035-58-9/Thromboplastin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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