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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1993-5-19
pubmed:abstractText
Factor Xa is a central procoagulant enzyme, linking the intrinsic and extrinsic activation mechanisms to the final common pathway of coagulation. To assess its contribution to pathologic thrombosis, studies were performed in a canine coronary thrombosis model. Thrombus formation was initiated by the application of electric current via a needle electrode placed in the lumen of the left circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycinyl-arginyl-factor Xa (Xai), a competitive inhibitor of factor Xa assembly into the prothrombinase complex, Factor X, or heparin. Animals infused with saline or factor X (300 micrograms/kg) developed total occlusion of the vessel due to a fibrin/platelet thrombus in 70 +/- 11 minutes (36 of 36 animals) and 74 +/- 13 minutes (8 of 8 animals), respectively. In contrast, infusion of Xai prevented thrombus formation completely at a dose of 300 micrograms/kg (8 of 8 animals). As the dose of Xai was decreased, its antithrombotic effect was diminished, with a patency rate of only 2 of 6 animals at a dose of 90 micrograms/kg. Xai at 300 micrograms/kg prevented the accumulation of 125I-fibrinogen/fibrin at the site of the coronary thrombus by approximately 63% and decreased deposition of 111In-labeled platelets by approximately 57%. Hemostatic parameters of animals infused with Xai demonstrated prolongation of the PT and dose-dependent increased extravascular bleeding tendency. These data indicate that factor Xa has a comparably important role in thrombus formation and extravascular hemostasis, and contrast with previous results in this same animal model in which IXai selectively prevented clotting in the coronary vasculature.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2059-66
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Active site-blocked factor Xa prevents thrombus formation in the coronary vasculature in parallel with inhibition of extravascular coagulation in a canine thrombosis model.
pubmed:affiliation
Division of Cardiology, University of Texas Medical School, Houston 77225.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't