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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2620-2621. This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bauer, K. A. Search for Related Content PubMed Articles by Bauer, K. A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS Comment on Butenas et al, page 2764 Functional tissue factor in blood? Kenneth A. Bauer VA BOSTON HEALTHCARE SYSTEM, HARVARD MEDICAL SCHOOL Several lines of evidence suggest that blood-borne tissue factor can promote thrombus growth. This study demonstrates that the amount of functional tissue factor in the blood of healthy individuals under nonflow conditions is vanishingly small. A report by Giesen et al1 in 1999 led to a resurgence of interest in the hypothesis that blood-borne tissue factor plays an important role in thrombogenesis, thereby challenging the traditional view that the dominant tissue factor source is the vascular wall. Some of the tissue factor molecules in blood are trun-cated or result from alternative splicing of tissue factor mRNA2 and lack the transmembrane domain. Several studies have demonstrated that tissue factor antigen is present in plasma and the levels can be elevated in a number of disease states associated with increased coagulation activation. Plasma tissue factor antigen levels have varied considerably between studies, and levels in young healthy individuals are reported to range from undetectable up to the picomolar range. There has however been controversy as to whether blood-borne tissue factor is functionally active under physiologic conditions. In live mice, it has been demonstrated that blood-borne tissue factor accumulates in newly formed thrombi via monocyte-derived microparticles in a process dependent upon P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1).3 To assess the functional significance of blood-borne tissue factor relative to vascular wall tissue factor under physiologic conditions, 2 groups have studied thrombus formation in bone marrow transplant chimeras of low–tissue factor mice and wild-type mice. Using intravital microscopy to study thrombus formation following laser-induced arterial injury, Chou et al4 concluded that tissue factor on hematopoietic cell–associated microparticles contributes significantly to thrombus propagation. However, Day et al5 found that thrombus formation following either carotid artery injury or inferior vena caval ligation was driven primarily by vascular wall tissue factor as opposed to blood-borne tissue factor. The reasons for the different results of the 2 studies are likely due to differences in the extent of vessel wall damage and the exposure of vessel wall tissue factor as well as the absence of circulating microparticles in a ligation thrombosis model. In this issue of Blood, Butenas and colleagues provide convincing data that the level of functional tissue factor in nonflowing blood of healthy volunteers cannot exceed 20 fM. In addition, they were unable to identify tissue factor activity or antigen on quiescent or ionophore-stimulated platelets of healthy individuals. There is considerable interest in assessing the role of blood-borne tissue factor in the pathogenesis of hypercoagulable states in association with diseases such as cancer, sepsis, and sickle cell disease. A major challenge for the field will be the development of assays for measuring functional tissue factor forms in blood that are physiologically relevant. As pointed out by Butenas et al, one must be cautious in interpreting tissue factor activity assays that use very large (ie, supraphysiologic) amounts of added factor VIIa. There are clearly key mysteries that require unraveling with regard to the role of blood-borne tissue factor in the thrombotic process. References Giesen PL, Rauch U, Borhrmann B, et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci U S A. 1999;96: 2311-2315.[Abstract/Free Full Text] Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y. Alternatively spliced human tissue factor: a circulating, soluble thrombogenic protein. Nature Med. 2003;9: 458-462.[CrossRef][Medline] [Order article via Infotrieve] Falati S, Liu Q, Gross P, et al. Accumulation of tissue factor into developing thrombi in vivo is dependent upon microparticle P-selectin glycoprotein ligand 1 and platelet P-selectin. J Exp Med. 2003;197: 1585-1598.[Abstract/Free Full Text] Chou J, Mackman N, Merrill-Skoloff G, Pedersen B, Furie BC, Furie B. Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation. Blood. 2004;104: 3190-3197.[Abstract/Free Full Text] Day SM, Reeve JL, Pedersen B, et al. Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood. 2004;105: 192-198. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Tissue factor activity in whole blood Saulius Butenas, Beth A. Bouchard, Kathleen E. Brummel-Ziedins, Behnaz Parhami-Seren, and Kenneth G. Mann Blood 2005 105: 2764-2770. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bauer, K. A. Search for Related Content PubMed Articles by Bauer, K. A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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