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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2764-2770.
Prepublished online as a Blood First Edition Paper on December 16, 2004; DOI 10.1182/blood-2004-09-3567.
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Submitted September 14, 2004
Accepted December 1, 2004
Tissue Factor Activity in Whole Blood
Saulius Butenas*, Beth A Bouchard, Kathleen E Brummel-Ziedins, Behnaz Parhami-Seren, and Kenneth G Mann
Department of Biochemistry, University of Vermont, Burlington, Vermont, USA
* Corresponding author; email: saulius.butenas{at}uvm.edu.
Tissue factor (TF) is an integral membrane protein essential for hemostasis. During the last 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 min 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 16-20 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 non-stimulated whole blood, while in 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.

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