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DOI: 10.1055/s-0032-1301410
Tissue Factor Pathway Inhibitor: New Insights into an Old Inhibitor
Publication History
Publication Date:
08 February 2012 (online)
Abstract
Blood coagulation in vivo is triggered by the tissue factor (TF) pathway. The major physiological regulator of this pathway is tissue factor pathway inhibitor (TFPI), a Kunitz-type inhibitor that regulates the activity of the TF-factor VIIa complex in a factor Xa-dependent manner, thus controlling the generation of thrombin and ultimately, fibrin. Although some of the in vivo and in vitro effects of TFPI have been described for nearly a century, the bulk of the research that has elucidated the physiology of this inhibitor has only occurred in the past 25 years. Despite this, many questions remain. This review will highlight the recent advances in knowledge related to TFPI, with an emphasis on new insights into its physiology, association with disease, and possible use as a therapeutic anticoagulant.
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References
- 1 Sanders NL, Bajaj SP, Zivelin A, Rapaport SI. Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component. Blood 1985; 66 (1) 204-212
- 2 Huang ZF, Broze Jr G. Consequences of tissue factor pathway inhibitor gene-disruption in mice. Thromb Haemost 1997; 78 (1) 699-704
- 3 Huang ZF, Higuchi D, Lasky N, Broze Jr GJ. Tissue factor pathway inhibitor gene disruption produces intrauterine lethality in mice. Blood 1997; 90 (3) 944-951
- 4 Loeb L, Fleisher MS, Tuttle L. The interaction between blood serum and tissue extract in the coagulation of the blood: I. The combined action of serum and tissue extract on fluoride, hirudin, and peptone plasma; the effect of heating on the serum. J Biol Chem 1922; 51: 461-483
- 5 Loeb L, Fleisher MS, Tuttle L. The interaction between blood serum and tissue extract in the coagulation of the blood: II. A comparison between the effects of the stroma of erythrocytes and of tissue extracts, unheated and heated, on the coagulation of the blood, and on the mechanism of the interaction of these substances with blood serum. J Biol Chem 1922; 51: 485-506
- 6 Schneider CL. The active principle of placental toxin; thromboplastin; its inactivator in blood; antithromboplastin. Am J Physiol 1947; 149 (1) 123-129
- 7 Thomas L. Studies on the intravascular thromboplastic effect of tissue suspensions in mice: a factor in normal rabbit serum which inhibits the thromboplastic effect of the sedimentable tissue component. Bull Johns Hopkins Hosp 1947; 81 (1) 26-42
- 8 Marciniak E, Tsukamura S. Two progressive inhibitors of factor Xa in human blood. Br J Haematol 1972; 22 (3) 341-351
- 9 Barrowcliffe TW, Eggleton CA, Stocks J. Studies of anti-Xa activity in human plasma. II: the role of lipoproteins. Thromb Res 1982; 27 (2) 185-195
- 10 Carson SD. Plasma high density lipoproteins inhibit the activation of coagulation factor X by factor VIIa and tissue factor. FEBS Lett 1981; 132 (1) 37-40
- 11 Marlar RA, Kleiss AJ, Griffin JH. An alternative extrinsic pathway of human blood coagulation. Blood 1982; 60 (6) 1353-1358
- 12 Broze Jr GJ, Miletich JP. Isolation of the tissue factor inhibitor produced by HepG2 hepatoma cells. Proc Natl Acad Sci U S A 1987; 84 (7) 1886-1890
- 13 Hubbard AR, Jennings CA. Inhibition of tissue thromboplastin-mediated blood coagulation. Thromb Res 1986; 42 (4) 489-498
- 14 Hjort PF. Intermediate reactions in the coagulation of blood with tissue thromboplastin; convertin, accelerin, prothrombinase. Scand J Clin Lab Invest 1957; 9 (Suppl 27) 1-183
- 15 Rao LV, Rapaport SI. Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation. Blood 1987; 69 (2) 645-651
- 16 Broze Jr GJ, Warren LA, Girard JJ, Miletich JP. Isolation of the lipoprotein associated coagulation inhibitor produced by HepG2 (human hepatoma) cells using bovine factor Xa affinity chromatography. Thromb Res 1987; 48 (2) 253-259
- 17 Wun TC, Kretzmer KK, Girard TJ, Miletich JP, Broze Jr GJ. Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. J Biol Chem 1988; 263 (13) 6001-6004
- 18 Broze Jr GJ, Lange GW, Duffin KL, MacPhail L. Heterogeneity of plasma tissue factor pathway inhibitor. Blood Coagul Fibrinolysis 1994; 5 (4) 551-559
- 19 Hansen JB, Huseby KR, Huseby NE, Ezban M, Nordøy A. Tissue factor pathway inhibitor in complex with low density lipoprotein isolated from human plasma does not possess anticoagulant function in tissue factor-induced coagulation in vitro. Thromb Res 1997; 85 (5) 413-425
- 20 Nordfang O, Bjørn SE, Valentin S , et al. The C-terminus of tissue factor pathway inhibitor is essential to its anticoagulant activity. Biochemistry 1991; 30 (43) 10371-10376
- 21 Valentin S, Nordfang O, Bregengård C, Wildgoose P. Evidence that the C-terminus of tissue factor pathway inhibitor (TFPI) is essential for its in vitro and in vivo interaction with lipoproteins. Blood Coagul Fibrinolysis 1993; 4 (5) 713-720
- 22 Wesselschmidt R, Likert K, Girard T, Wun TC, Broze Jr GJ. Tissue factor pathway inhibitor: the carboxy-terminus is required for optimal inhibition of factor Xa. Blood 1992; 79 (8) 2004-2010
- 23 Piro O, Broze Jr GJ. Role for the Kunitz-3 domain of tissue factor pathway inhibitor-alpha in cell surface binding. Circulation 2004; 110 (23) 3567-3572
- 24 Mine S, Yamazaki T, Miyata T, Hara S, Kato H. Structural mechanism for heparin-binding of the third Kunitz domain of human tissue factor pathway inhibitor. Biochemistry 2002; 41 (1) 78-85
- 25 Nordfang O, Bjørn SE, Valentin S , et al. The C-terminus of tissue factor pathway inhibitor is essential to its anticoagulant activity. Biochemistry 1991; 30 (43) 10371-10376
- 26 Wesselschmidt R, Likert K, Girard T, Wun TC, Broze Jr GJ. Tissue factor pathway inhibitor: the carboxy-terminus is required for optimal inhibition of factor Xa. Blood 1992; 79 (8) 2004-2010
- 27 Werling RW, Zacharski LR, Kisiel W, Bajaj SP, Memoli VA, Rousseau SM. Distribution of tissue factor pathway inhibitor in normal and malignant human tissues. Thromb Haemost 1993; 69 (4) 366-369
- 28 Maroney SA, Haberichter SL, Friese P , et al. Active tissue factor pathway inhibitor is expressed on the surface of coated platelets. Blood 2007; 109 (5) 1931-1937
- 29 Novotny WF, Girard TJ, Miletich JP, Broze Jr GJ. Purification and characterization of the lipoprotein-associated coagulation inhibitor from human plasma. J Biol Chem 1989; 264 (31) 18832-18837
- 30 Sandset PM. Tissue factor pathway inhibitor (TFPI)—an update. Haemostasis 1996; 26 (Suppl 4) 154-165
- 31 McGee MP, Foster S, Wang X. Simultaneous expression of tissue factor and tissue factor pathway inhibitor by human monocytes. A potential mechanism for localized control of blood coagulation. J Exp Med 1994; 179 (6) 1847-1854
- 32 van der Logt CP, Dirven RJ, Reitsma PH, Bertina RM. Expression of tissue factor and tissue factor pathway inhibitor in monocytes in response to bacterial lipopolysaccharide and phorbolester. Blood Coagul Fibrinolysis 1994; 5 (2) 211-220
- 33 Petit L, Lesnik P, Dachet C, Moreau M, Chapman MJ. Tissue factor pathway inhibitor is expressed by human monocyte-derived macrophages : relationship to tissue factor induction by cholesterol and oxidized LDL. Arterioscler Thromb Vasc Biol 1999; 19 (2) 309-315
- 34 Bajaj MS, Kuppuswamy MN, Saito H, Spitzer SG, Bajaj SP. Cultured normal human hepatocytes do not synthesize lipoprotein-associated coagulation inhibitor: evidence that endothelium is the principal site of its synthesis. Proc Natl Acad Sci U S A 1990; 87 (22) 8869-8873
- 35 Bajaj MS, Steer S, Kuppuswamy MN, Kisiel W, Bajaj SP. Synthesis and expression of tissue factor pathway inhibitor by serum-stimulated fibroblasts, vascular smooth muscle cells and cardiac myocytes. Thromb Haemost 1999; 82 (6) 1663-1672
- 36 Broze Jr GJ, Girard TJ, Novotny WF. Regulation of coagulation by a multivalent Kunitz-type inhibitor. Biochemistry 1990; 29 (33) 7539-7546
- 37 Iversen N, Sandset PM, Abildgaard U, Torjesen PA. Binding of tissue factor pathway inhibitor to cultured endothelial cells-influence of glycosaminoglycans. Thromb Res 1996; 84 (4) 267-278
- 38 Lupu C, Goodwin CA, Westmuckett AD , et al. Tissue factor pathway inhibitor in endothelial cells colocalizes with glycolipid microdomains/caveolae. Regulatory mechanism(s) of the anticoagulant properties of the endothelium. Arterioscler Thromb Vasc Biol 1997; 17 (11) 2964-2974
- 39 Sevinsky JR, Rao LV, Ruf W. Ligand-induced protease receptor translocation into caveolae: a mechanism for regulating cell surface proteolysis of the tissue factor-dependent coagulation pathway. J Cell Biol 1996; 133 (2) 293-304
- 40 Lupu C, Lupu F, Dennehy U, Kakkar VV, Scully MF. Thrombin induces the redistribution and acute release of tissue factor pathway inhibitor from specific granules within human endothelial cells in culture. Arterioscler Thromb Vasc Biol 1995; 15 (11) 2055-2062
- 41 Marutsuka K, Hatakeyama K, Yamashita A, Sato Y, Sumiyoshi A, Asada Y. Adrenomedullin augments the release and production of tissue factor pathway inhibitor in human aortic endothelial cells. Cardiovasc Res 2003; 57 (1) 232-237
- 42 Hansen JB, Svensson B, Olsen R, Ezban M, Osterud B, Paulssen RH. Heparin induces synthesis and secretion of tissue factor pathway inhibitor from endothelial cells in vitro. Thromb Haemost 2000; 83 (6) 937-943
- 43 Lupu C, Poulsen E, Roquefeuil S, Westmuckett AD, Kakkar VV, Lupu F. Cellular effects of heparin on the production and release of tissue factor pathway inhibitor in human endothelial cells in culture. Arterioscler Thromb Vasc Biol 1999; 19 (9) 2251-2262
- 44 Bara L, Bloch MF, Zitoun D , et al. Comparative effects of enoxaparin and unfractionated heparin in healthy volunteers on prothrombin consumption in whole blood during coagulation, and release of tissue factor pathway inhibitor. Thromb Res 1993; 69 (5) 443-452
- 45 Kijowski R, Hoppensteadt D, Walenga J, Borris L, Lassen MR, Fareed J. Role of tissue factor pathway inhibitor in post surgical deep venous thrombosis (DVT) prophylaxis in patients treated with low molecular weight heparin. Thromb Res 1994; 74 (1) 53-64
- 46 Samama MM, Bara L, Gerotziafas GT. Mechanisms for the antithrombotic activity in man of low molecular weight heparins (LMWHs). Haemostasis 1994; 24 (2) 105-117
- 47 Hansen JB, Huseby KR, Huseby NE, Ezban M, Nordøy A. Tissue factor pathway inhibitor in complex with low density lipoprotein isolated from human plasma does not possess anticoagulant function in tissue factor-induced coagulation in vitro. Thromb Res 1997; 85 (5) 413-425
- 48 Lesnik P, Vonica A, Guérin M, Moreau M, Chapman MJ. Anticoagulant activity of tissue factor pathway inhibitor in human plasma is preferentially associated with dense subspecies of LDL and HDL and with Lp(a). Arterioscler Thromb 1993; 13 (7) 1066-1075
- 49 Ellery PE, Hardy K, Oostryck R, Adams MJ. Further insight into the heparin-releasable and glycosylphosphatidylinositollipid-anchored forms of tissue factor pathway inhibitor. Clin Appl Thromb Hemost 2008; 14 (3) 267-278
- 50 Maroney SA, Cunningham AC, Ferrel J , et al. A GPI-anchored co-receptor for tissue factor pathway inhibitor controls its intracellular trafficking and cell surface expression. J Thromb Haemost 2006; 4 (5) 1114-1124
- 51 Mast AE, Acharya N, Malecha MJ, Hall CL, Dietzen DJ. Characterization of the association of tissue factor pathway inhibitor with human placenta. Arterioscler Thromb Vasc Biol 2002; 22 (12) 2099-2104
- 52 Ott I, Miyagi Y, Miyazaki K , et al. Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor. Arterioscler Thromb Vasc Biol 2000; 20 (3) 874-882
- 53 Zhang J, Piro O, Lu L, Broze Jr GJ. Glycosyl phosphatidylinositol anchorage of tissue factor pathway inhibitor. Circulation 2003; 108 (5) 623-627
- 54 Maroney SA, Ellery PE, Mast AE. Alternatively spliced isoforms of tissue factor pathway inhibitor. Thromb Res 2010; 125 (Suppl 1) S52-S56
- 55 O’Brien LM, Mastri M, Fay PJ. Regulation of factor VIIIa by human activated protein C and protein S: inactivation of cofactor in the intrinsic factor Xase. Blood 2000; 95 (5) 1714-1720
- 56 Rosing J, Hoekema L, Nicolaes GA , et al. Effects of protein S and factor Xa on peptide bond cleavages during inactivation of factor Va and factor VaR506Q by activated protein C. J Biol Chem 1995; 270 (46) 27852-27858
- 57 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311 (24) 1525-1528
- 58 Comp PC, Nixon RR, Cooper MR, Esmon CT. Familial protein S deficiency is associated with recurrent thrombosis. J Clin Invest 1984; 74 (6) 2082-2088
- 59 Schwarz HP, Fischer M, Hopmeier P, Batard MA, Griffin JH. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64 (6) 1297-1300
- 60 van’t Veer C, Hackeng TM, Biesbroeck D, Sixma JJ, Bouma BN. Increased prothrombin activation in protein S-deficient plasma under flow conditions on endothelial cell matrix: an independent anticoagulant function of protein S in plasma. Blood 1995; 85 (7) 1815-1821
- 61 Hackeng TM, Seré KM, Tans G, Rosing J. Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor. Proc Natl Acad Sci U S A 2006; 103 (9) 3106-3111
- 62 Ndonwi M, Broze Jr G. Protein S enhances the tissue factor pathway inhibitor inhibition of factor Xa but not its inhibition of factor VIIa-tissue factor. J Thromb Haemost 2008; 6 (6) 1044-1046
- 63 Castoldi E, Simioni P, Tormene D, Rosing J, Hackeng TM. Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma. J Thromb Haemost 2010; 8 (2) 294-300
- 64 Giesen PL, Rauch U, Bohrmann B , et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci U S A 1999; 96 (5) 2311-2315
- 65 Mast AE, Stadanlick JE, Lockett JM, Dietzen DJ, Hasty KA, Hall CL. Tissue factor pathway inhibitor binds to platelet thrombospondin-1. J Biol Chem 2000; 275 (41) 31715-31721
- 66 Crawley JT, Lane DA. The haemostatic role of tissue factor pathway inhibitor. Arterioscler Thromb Vasc Biol 2008; 28 (2) 233-242
- 67 Ariëns RA, Alberio G, Moia M, Mannucci PM. Low levels of heparin-releasable tissue factor pathway inhibitor in young patients with thrombosis. Thromb Haemost 1999; 81 (2) 203-207
- 68 Dahm A, Van Hylckama Vlieg A, Bendz B, Rosendaal F, Bertina RM, Sandset PM. Low levels of tissue factor pathway inhibitor (TFPI) increase the risk of venous thrombosis. Blood 2003; 101 (11) 4387-4392
- 69 Llobet D, Falkon L, Mateo J , et al. Low levels of tissue factor pathway inhibitor (TFPI) in two out of three members of a family with thrombophilia. Thromb Res 1995; 80 (5) 413-418
- 70 Adams MJ, Oostryck R. A comparative study of functional assays for tissue factor pathway inhibitor using normal plasma and clinical samples. Blood Coagul Fibrinolysis 2000; 11 (4) 327-333
- 71 Bognacki J, Hammelburger J. Functional and immunologic methods for the measurement of human tissue factor pathway inhibitor. Blood Coagul Fibrinolysis 1995; 6 (Suppl 1) S65-S72
- 72 Skretting G, Stavik B, Landvik NE , et al. Functional characterization of polymorphisms in the human TFPI gene. Biochem Biophys Res Commun 2010; 397 (1) 106-111
- 73 Amini Nekoo A, Iles D. Analysis of a T-287C polymorphism in the tissue factor pathway inhibitor gene and identification of a repressor element in the promoter. Thromb Res 2008; 121 (6) 813-819
- 74 Eitzman DT, Westrick RJ, Bi X , et al. Lethal perinatal thrombosis in mice resulting from the interaction of tissue factor pathway inhibitor deficiency and factor V Leiden. Circulation 2002; 105 (18) 2139-2142
- 75 Lincz LF, Adams MJ, Scorgie FE, Thom J, Baker RI, Seldon M. Polymorphisms of the tissue factor pathway inhibitor gene are associated with venous thromboembolism in the antiphospholipid syndrome and carriers of factor V Leiden. Blood Coagul Fibrinolysis 2007; 18 (6) 559-564
- 76 Bajaj MS, Bajaj SP. Tissue factor pathway inhibitor: potential therapeutic applications. Thromb Haemost 1997; 78 (1) 471-477
- 77 Holst J, Lindblad B, Bergqvist D , et al. Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI1-161) in experimental venous thrombosis—a comparison with low molecular weight heparin. Thromb Haemost 1994; 71 (2) 214-219
- 78 Spokas EG, Wun TC. Venous thrombosis produced in the vena cava of rabbits by vascular damage and stasis. J Pharmacol Toxicol Methods 1992; 27 (4) 225-232
- 79 Bregengård C, Nordfang O, Wildgoose P, Svendsen O, Hedner U, Diness V. The effect of two-domain tissue factor pathway inhibitor on endotoxin-induced disseminated intravascular coagulation in rabbits. Blood Coagul Fibrinolysis 1993; 4 (5) 699-706
- 80 Camerota AJ, Creasey AA, Patla V, Larkin VA, Fink MP. Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis. J Infect Dis 1998; 177 (3) 668-676
- 81 Abendschein DR, Meng YY, Torr-Brown S, Sobel BE. Maintenance of coronary patency after fibrinolysis with tissue factor pathway inhibitor. Circulation 1995; 92 (4) 944-949
- 82 Badimon JJ, Lettino M, Toschi V , et al. Local inhibition of tissue factor reduces the thrombogenicity of disrupted human atherosclerotic plaques: effects of tissue factor pathway inhibitor on plaque thrombogenicity under flow conditions. Circulation 1999; 99 (14) 1780-1787
- 83 Brown DM, Kania NM, Choi ET , et al. Local irrigation with tissue factor pathway inhibitor inhibits intimal hyperplasia induced by arterial interventions. Arch Surg 1996; 131 (10) 1086-1090
- 84 Haskel EJ, Torr SR, Day KC , et al. Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor. Circulation 1991; 84 (2) 821-827
- 85 Khouri RK, Sherman R, Buncke Jr HJ , et al. A phase II trial of intraluminal irrigation with recombinant human tissue factor pathway inhibitor to prevent thrombosis in free flap surgery. Plast Reconstr Surg 2001; 107 (2) 408-415, discussion 416–418
- 86 de Jonge E, Dekkers PE, Creasey AA , et al. Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood 2000; 95 (4) 1124-1129
- 87 Abraham E, Reinhart K, Opal S , et al; OPTIMIST Trial Study Group. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003; 290 (2) 238-247
- 88 Abraham E, Reinhart K, Svoboda P , et al. Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study. Crit Care Med 2001; 29 (11) 2081-2089
- 89 Laterre PF. Beyond antibiotics in severe community-acquired pneumonia: the role and rationale for tissue factor pathway inhibition. Crit Care 2008; 12 (Suppl 6) S4
- 90 Wunderink RG, Laterre PF, Francois B , et al; CAPTIVATE Trial Group. Recombinant tissue factor pathway inhibitor in severe community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2011; 183 (11) 1561-1568
- 91 Adams M. Novel considerations in the pathogenesis of the antiphospholipid syndrome: involvement of the tissue factor pathway of blood coagulation. Semin Thromb Hemost 2008; 34 (3) 251-255