Levels of microparticle tissue factor activity correlate with coagulation activation in endotoxemic mice.
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.


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.


CONCLUSIONS
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.
Wang
J-G
JG
Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Manly
D
D
Kirchhofer
D
D
Pawlinski
R
R
Mackman
N
N
D000818:Animals; D001777:Blood Coagulation; D019446:Endotoxemia / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051379:Mice; D013925:Thromboplastin / Q000378:metabolism*
D013925:Thromboplastin