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DOI: 10.1055/s-0030-1265293
Tissue Factor and Tissue Factor Pathway Inhibitor as Key Regulators of Global Hemostasis: Measurement of Their Levels in Coagulation Assays
Publication History
Publication Date:
26 October 2010 (online)
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ABSTRACT
The tissue factor (TF)/factor (F)VIIa complex is the primary initiator of coagulation in vivo. Tissue factor pathway inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Deficiencies of either TF or TFPI have not been reported in humans, and a complete absence of either of these two proteins in mice is embryonically lethal. To maintain normal hemostasis, levels of TF and TFPI need to be balanced. Increased levels of TF can overwhelm the inhibitory capacity of TFPI, resulting in thrombosis. Decreased levels of TF are associated with bleeding. Global assays of coagulation are defined as tests capable of evaluating all components of the clotting cascade that are present in plasma. In these tests the thrombogenic surface is either provided by platelets or exogenous phospholipids. Clotting assays currently used in clinical practice are not designed to measure endogenous levels of TF and TFPI. Therefore, there is a need to develop sensitive and specific assays for measuring levels of functional TF and TFPI in whole blood and plasma. These assays could be useful in patient management in many scenarios.
KEYWORDS
Tissue factor - tissue factor pathway inhibitor - thrombosis - thromboelastography
REFERENCES
- 1 Gross P L, Weitz J I. New antithrombotic drugs. Clin Pharmacol Ther. 2009; 86(2) 139-146
- 2 Howard E L, Becker K C, Rusconi C P, Becker R C. Factor IXa inhibitors as novel anticoagulants. Arterioscler Thromb Vasc Biol. 2007; 27(4) 722-727
- 3 Mackman N, Taubman M. Tissue factor: past, present, and future. Arterioscler Thromb Vasc Biol. 2009; 29(12) 1986-1988
- 4 Tilley R, Mackman N. Tissue factor in hemostasis and thrombosis. Semin Thromb Hemost. 2006; 32(1) 5-10
- 5 Censarek P, Bobbe A, Grandoch M, Schrör K, Weber A A. Alternatively spliced human tissue factor (asHTF) is not pro-coagulant. Thromb Haemost. 2007; 97(1) 11-14
- 6 Bach R R. Tissue factor encryption. Arterioscler Thromb Vasc Biol. 2006; 26(3) 456-461
- 7 Maroney S A, Mast A E. Expression of tissue factor pathway inhibitor by endothelial cells and platelets. Transfus Apheresis Sci. 2008; 38(1) 9-14
- 8 Hackeng T M, Rosing J. Protein S as cofactor for TFPI. Arterioscler Thromb Vasc Biol. 2009; 29(12) 2015-2020
- 9 Heit J A. Cancer and venous thromboembolism: scope of the problem. Cancer Control. 2005; 12(Suppl 1) 5-10
- 10 Kasthuri R S, Taubman M B, Mackman N. Role of tissue factor in cancer. J Clin Oncol. 2009; 27(29) 4834-4838
- 11 Tesselaar M E, Romijn F P, Van Der Linden I K, Prins F A, Bertina R M, Osanto S. Microparticle-associated tissue factor activity: a link between cancer and thrombosis?. J Thromb Haemost. 2007; 5(3) 520-527
- 12 Khorana A A, Francis C W, Menzies K E et al.. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost. 2008; 6(11) 1983-1985
- 13 Dahm A, Van Hylckama Vlieg A, Bendz B, Rosendaal F, Bertina R M, Sandset P M. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis. Blood. 2003; 101(11) 4387-4392
- 14 Duering C, Kosch A, Langer C, Thedieck S, Nowak-Göttl U. Total tissue factor pathway inhibitor is an independent risk factor for symptomatic paediatric venous thromboembolism and stroke. Thromb Haemost. 2004; 92(4) 707-712
- 15 Ariëns R A, Alberio G, Moia M, Mannucci P M. Low levels of heparin-releasable tissue factor pathway inhibitor in young patients with thrombosis. Thromb Haemost. 1999; 81(2) 203-207
- 16 Bladbjerg E M, Madsen J S, Kristensen S R et al.. Effect of long-term hormone replacement therapy on tissue factor pathway inhibitor and thrombin activatable fibrinolysis inhibitor in healthy postmenopausal women: a randomized controlled study. J Thromb Haemost. 2003; 1(6) 1208-1214
- 17 Amini-Nekoo A, Futers T S, Moia M, Mannucci P M, Grant P J, Ariëns R A. Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis. Br J Haematol. 2001; 113(2) 537-543
- 18 Sidelmann J J, Bladbjerg E M, Gram J, Münster A M, Jespersen J. Tissue factor pathway inhibitor relates to fibrin degradation in patients with acute deep venous thrombosis. Blood Coagul Fibrinolysis. 2008; 19(5) 405-409
- 19 Hoke M, Kyrle P A, Minar E et al.. Tissue factor pathway inhibitor and the risk of recurrent venous thromboembolism. Thromb Haemost. 2005; 94(4) 787-790
- 20 Ollivier V, Wang J, Manly D et al.. Detection of endogenous tissue factor levels in plasma using the calibrated automated thrombogram assay. Thromb Res. 2010; 125(1) 90-96
- 21 Haubold K, Rink M, Spath B et al.. Tissue factor procoagulant activity of plasma microparticles is increased in patients with early-stage prostate cancer. Thromb Haemost. 2009; 101(6) 1147-1155
- 22 Santucci R A, Erlich J, Labriola J et al.. Measurement of tissue factor activity in whole blood. Thromb Haemost. 2000; 83(3) 445-454
- 23 Marsik C, Quehenberger P, Mackman N, Osterud B, Luther T, Jilma B. Validation of a novel tissue factor assay in experimental human endotoxemia. Thromb Res. 2003; 111(4–5) 311-315
- 24 Zillmann A, Luther T, Müller I et al.. Platelet-associated tissue factor contributes to the collagen-triggered activation of blood coagulation. Biochem Biophys Res Commun. 2001; 281(2) 603-609
- 25 Koch L, Hofer S, Weigand M A, Frommhold D, Poeschl J. Lipopolysaccharide-induced activation of coagulation in neonatal cord and adult blood monitored by thrombelastography. Thromb Res. 2009; 124(4) 463-467
- 26 Parhami-Seren B, Butenas S, Krudysz-Amblo J, Mann K G. Immunologic quantitation of tissue factors. J Thromb Haemost. 2006; 4(8) 1747-1755
- 27 Luther T, Flössel C, Hietschhold V, Koslowski R, Müller M. Flow cytometric analysis of tissue factor (TF) expression on stimulated monocytes—comparison to procoagulant activity of mononuclear blood cells. Blut. 1990; 61(6) 375-378
- 28 Shet A S, Aras O, Gupta K et al.. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood. 2003; 102(7) 2678-2683
- 29 Zwicker J I, Liebman H A, Neuberg D et al.. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res. 2009; 15(22) 6830-6840
- 30 Bogdanov V Y, Cimmino G, Tardos J G, Tunstead J R, Badimon J J. Assessment of plasma tissue factor activity in patients presenting with coronary artery disease: limitations of a commercial assay. J Thromb Haemost. 2009; 7(5) 894-897
- 31 Key N S, Slungaard A, Dandelet L et al.. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood. 1998; 91(11) 4216-4223
- 32 Aras O, Shet A, Bach R R et al.. Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. Blood. 2004; 103(12) 4545-4553
Nigel MackmanPh.D.
UNC Chapel Hill, 917 Mary Ellen Jones Building
CB7035, Chapel Hill, NC 27599
Email: nmackman@med.unc.edu