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Blood, 1 January 2005, Vol. 105, No. 1, pp. 192-198. Prepublished online as a Blood First Edition Paper on August 31, 2004; DOI 10.1182/blood-2004-06-2225. This Article Full Text (PDF) All Versions of this Article: 2004-06-2225v1 105/1/192    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Day, S. M Articles by Fay, W. P Search for Related Content PubMed PubMed Citation Articles by Day, S. M Articles by Fay, W. P Related Collections Related Article in Blood Online Related Letters in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 14, 2004 Accepted August 17, 2004 Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall Sharlene M Day*, Jennifer L Reeve, Brian Pedersen, Diana M Farris, Daniel D Myers, Michael Im, Thomas W Wakefield, Nigel Mackman, and William P Fay Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA * Corresponding author; email: sday{at}umich.edu. Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe tissue factor deficiency (i.e. TF-/-, hTF-Tg+, or "low-TF") demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low, and was markedly exceeded by that present in the vessel wall. Therefore, while thrombosis after vascular injury is tissue factor-dependent, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Clotting hits the wall James H. Morrissey Blood 2005 105: 3-4. [Full Text] [PDF] Related Letters in Blood Online: Up against the wall James J. Hathcock and Yale Nemerson Blood 2005 106: 1505. [Full Text] [PDF] Tissue-factor-endowed leukocytes do cause thrombosis Julian Niemetz, Sharlene M. Day, Nigel Mackman, and William P. Fay Blood 2005 106: 1506-1507. [Full Text] [PDF] This article has been cited by other articles: S. Butenas, T. Orfeo, and K. G. Mann Tissue Factor in Coagulation: Which? Where? When? Arterioscler Thromb Vasc Biol, December 1, 2009; 29(12): 1989 - 1996. [Abstract] [Full Text] [PDF] R. A. Campbell, K. 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