Document Detail


Levels of microparticle tissue factor activity correlate with coagulation activation in endotoxemic mice.
MedLine Citation:
PMID:  19422446     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Tissue factor (TF) is present in blood in various forms, including small membrane vesicles called microparticles (MPs). Elevated levels of these MPs appear to play a role in the pathogenesis of thrombosis in a variety of diseases, including sepsis.
OBJECTIVE: Measure levels of MP TF activity and activation of coagulation in control and endotoxemic mice.
MATERIALS AND METHODS: MPs were prepared from plasma by centrifugation. The procoagulant activity (PCA) of MPs was measured using a two-stage chromogenic assay. We also measured levels of thrombin-antithrombin and the number of MPs.
RESULTS: Lipopolysaccharide (LPS) increased MP PCA in wild-type mice; this PCA was significantly reduced by an anti-mouse TF antibody (1H1) but not with an anti-human TF antibody (HTF-1). Conversely, in mice expressing only human TF, MP PCA was inhibited by HTF-1 but not 1H1. MPs from wild-type mice had 6-fold higher levels of PCA using mouse factor (F)VIIa compared with human FVIIa, which is consistent with reported species-specific differences in FVIIa. Mice expressing low levels of human TF had significantly lower levels of MP TF activity and TAT than mice expressing high levels of human TF; however, there were similar levels of phosphatidylserine (PS)-positive MPs. Importantly, levels of MP TF activity in wild-type mice correlated with levels of TAT but not with PS-positive MPs in endotoxemic mice.
CONCLUSION: These results suggest that the levels of TF-positive MPs can be used as a biomarker for evaluating the risk of disseminated intravascular coagulation in endotoxemia.
Authors:
J-G Wang; D Manly; D Kirchhofer; R Pawlinski; N Mackman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-04-27
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  7     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-06     Completed Date:  2009-10-22     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  1092-8     Citation Subset:  IM    
Affiliation:
Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Coagulation*
Endotoxemia / physiopathology*
Enzyme-Linked Immunosorbent Assay
Humans
Mice
Thromboplastin / metabolism*
Grant Support
ID/Acronym/Agency:
R01 HL048872-09/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
9035-58-9/Thromboplastin
Comments/Corrections

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