title: Tissue factor activity in whole blood.
abstract: Tissue factor (TF) is an integral membrane protein essential for hemostasis. During the past several years, a number of studies have suggested that physiologically active TF circulates in blood at concentrations greater than 30 pM either as a component of blood cells and microparticles or as a soluble plasma protein. In our studies using contact pathway-inhibited blood or plasma containing activated platelets, typically no clot is observed for 20 minutes in the absence of exogenous TF. An inhibitory anti-TF antibody also has no effect on the clotting time in the absence of exogenous TF. The addition of TF to whole blood at a concentration as low as 16 to 20 fM results in pronounced acceleration of clot formation. The presence of potential platelet TF activity was evaluated using ionophore-treated platelets and employing functional and immunoassays. No detectable TF activity or antigen was observed on quiescent or ionophore-stimulated platelets. Similarly, no TF antigen was detected on mononuclear cells in nonstimulated whole blood, whereas in lipopolysaccharide (LPS)-stimulated blood a significant fraction of monocytes express TF. Our data indicate that the concentration of physiologically active TF in non-cytokine-stimulated blood from healthy individuals cannot exceed and is probably lower than 20 fM.
authors.affiliation: University of Vermont, Department of Biochemistry, Given Building, 89 Beaumont Ave, Burlington, VT 05405-0068, USA. saulius.butenas@uvm.edu
authors.forename: Saulius
authors.initials: S
authors.lastname: Butenas
authors.forename: Beth A
authors.initials: BA
authors.lastname: Bouchard
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Brummel-Ziedins
authors.forename: Behnaz
authors.initials: B
authors.lastname: Parhami-Seren
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Mann
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D001769:Blood; D001774:Blood Chemical Analysis / Q000379:methods; D001777:Blood Coagulation / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010949:Plasma; D013925:Thromboplastin / Q000276:immunology / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D013925:Thromboplastin