• 1
    Mann KG. Thrombin formation. Chest 2003; 124: 4S10S.
  • 2
    Giesen PL, Rauch U, Bohrmann B, Kling D, Roque M, Fallon JT, Badimon JJ, Himber J, Riederer MA, Nemerson Y. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci U S A 1999; 96: 23115.
  • 3
    Del Conde I, Shrimpton CN, Thiagarajan P, Lopez JA. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 2005; 106: 160411.
  • 4
    Panes O, Matus V, Saez CG, Quiroga T, Pereira J, Mezzano D. Human platelets synthesize and express functional tissue factor. Blood 2007; 109: 524250.
  • 5
    Schwertz H, Tolley ND, Foulks JM, Denis MM, Risenmay BW, Buerke M, Tilley RE, Rondina MT, Harris EM, Kraiss LW, Mackman N, Zimmerman GA, Weyrich AS. Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenicity of human platelets. J Exp Med 2006; 203: 243340.
  • 6
    Shaw AW, Pureza VS, Sligar SG, Morrissey JH. The local phospholipid environment modulates the activation of blood clotting. J Biol Chem 2007; 282: 655663.
  • 7
    Monroe DM, Hoffman M. Coagulation factor interaction with platelets. Thromb Haemost 2002; 88: 179.
  • 8
    Himber J, Kirchhofer D, Riederer M, Tschopp TB, Steiner B, Roux SP. Dissociation of antithrombotic effect and bleeding time prolongation in rabbits by inhibiting tissue factor function. Thromb Haemost 1997; 78: 11429.
  • 9
    Taubman MB, Fallon JT, Schecter AD, Giesen P, Mendlowitz M, Fyfe BS, Marmur JD, Nemerson Y. Tissue factor in the pathogenesis of atherosclerosis. Thromb Haemost 1997; 78: 2004.
  • 10
    Kaikita K, Ogawa H, Yasue H, Takeya M, Takahashi K, Saito T, Hayasaki K, Horiuchi K, Takizawa A, Kamikubo Y, Nakamura S. Tissue factor expression on macrophages in coronary plaques in patients with unstable angina. Arterioscler Thromb Vasc Biol 1997; 17: 22327.
  • 11
    Badimon JJ, Lettino M, Toschi V, Fuster V, Berrozpe M, Chesebro JH, Badimon L. 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: 17807.
  • 12
    Marmur JD, Sharma SK, Weinrauch M, Kantrowitz N, Dangas G, Kokinakkis S, Ambrose JA. Thrombin generation and activity during coronary angioplasty: influence of angiographic lesion morphology. J Invasive Cardiol 1997; 9: 4106.
  • 13
    Jude B, Agraou B, McFadden EP, Susen S, Bauters C, Lepelley P, Vanhaesbroucke C, Devos P, Cosson A, Asseman P. Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina. Circulation 1994; 90: 16628.
  • 14
    Ott I, Neumann FJ, Kenngott S, Gawaz M, Schomig A. Procoagulant inflammatory responses of monocytes after direct balloon angioplasty in acute myocardial infarction. Am J Cardiol 1998; 82: 93842.
  • 15
    Steppich B, Mattisek C, Sobczyk D, Kastrati A, Schomig A, Ott I. Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction. Thromb Haemost 2005; 93: 359.
  • 16
    Erlich JH, Boyle EM, Labriola J, Kovacich JC, Santucci RA, Fearns C, Morgan EN, Yun W, Luther T, Kojikawa O, Martin TR, Pohlman TH, Verrier ED, Mackman N. Inhibition of the tissue factor-thrombin pathway limits infarct size after myocardial ischemia-reperfusion injury by reducing inflammation. Am J Pathol 2000; 157: 184962.
  • 17
    Asada Y, Hara S, Tsuneyoshi A, Hatakeyama K, Kisanuki A, Marutsuka K, Sato Y, Kamikubo Y, Sumiyoshi A. Fibrin-rich and platelet-rich thrombus formation on neointima: recombinant tissue factor pathway inhibitor prevents fibrin formation and neointimal development following repeated balloon injury of rabbit aorta. Thromb Haemost 1998; 80: 50611.
  • 18
    Himber J, Wohlgensinger C, Roux S, Damico LA, Fallon JT, Kirchhofer D, Nemerson Y, Riederer MA. Inhibition of tissue factor limits the growth of venous thrombus in the rabbit. J Thromb Haemost 2003; 1: 88995.
  • 19
    Taylor FB Jr, Chang A, Ruf W, Morrissey JH, Hinshaw L, Catlett R, Blick K, Edgington TS. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 12734.
  • 20
    Ruf W, Yokota N, Schaffner F. Tissue factor in cancer progression and angiogenesis. Thromb Res 2010; 125 (Suppl. 2): S368.
  • 21
    Ott I, Weigand B, Michl R, Seitz I, Sabbari-Erfani N, Neumann FJ, Schomig A. Tissue factor cytoplasmic domain stimulates migration by activation of the GTPase Rac1 and the mitogen-activated protein kinase p38. Circulation 2005; 111: 34955.
  • 22
    Broze GJ Jr. The rediscovery and isolation of TFPI. J Thromb Haemost 2003; 1: 16715.
  • 23
    Hedner U, Erhardtsen E. Future possibilities in the regulation of the extrinsic pathway: rFVIIa and TFPI. Ann Med 2000; 32 (Suppl. 1): 6872.
  • 24
    de Jonge E, Dekkers PE, Creasey AA, Hack CE, Paulson SK, Karim A, Kesecioglu J, Levi M, van Deventer SJ, van Der Poll T. Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood 2000; 95: 11249.
  • 25
    Abraham E, Reinhart K, Svoboda P, Seibert A, Olthoff D, Dal Nogare A, Postier R, Hempelmann G, Butler T, Martin E, Zwingelstein C, Percell S, Shu V, Leighton A, Creasey AA. 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: 20819.
  • 26
    Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Svoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Peckelsen C, De Deyne C, Postier R, Pettila V, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobias J, Poole L, Stolzenbach JC, Creasey AA. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 2003; 290: 23847.
  • 27
    Rao LV, Ezban M. Active site-blocked activated factor VII as an effective antithrombotic agent: mechanism of action. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 1): S135143.
  • 28
    Harker LA, Hanson SR, Wilcox JN, Kelly AB. Antithrombotic and antilesion benefits without hemorrhagic risks by inhibiting tissue factor pathway. Haemostasis 1996; 26 (Suppl. 1): 7682.
  • 29
    Golino P, Ragni M, Cirillo P, D’Andrea D, Scognamiglio A, Ravera A, Buono C, Ezban M, Corcione N, Vigorito F, Condorelli M, Chiariello M. Antithrombotic effects of recombinant human, active site-blocked factor VIIa in a rabbit model of recurrent arterial thrombosis. Circ Res 1998; 82: 3946.
  • 30
    Lev EI, Marmur JD, Zdravkovic M, Osende JI, Robbins J, Delfin JA, Richard M, Erhardtsen E, Thomsen MS, Lincoff AM, Badimon JJ. Antithrombotic effect of tissue factor inhibition by inactivated factor VIIa: an ex vivo human study. Arterioscler Thromb Vasc Biol 2002; 22: 103641.
  • 31
    Lincoff A. First clinical investigation of a tissue-factor inhibitor administered during percutaneous coronary revascularization: a randomized, double-blinded, dose-escalation trial – assessing safety and efficacy of FFR-FVIIa in percutaneous transluminal coronary angioplasty (ASIS) trial. J Am Coll Cardiol 2000; 36: 31025.
  • 32
    Dennis MS, Eigenbrot C, Skelton NJ, Ultsch MH, Santell L, Dwyer MA, O’Connell MP, Lazarus RA. Peptide exosite inhibitors of factor VIIa as anticoagulants. Nature 2000; 404: 46570.
  • 33
    Dennis MS, Roberge M, Quan C, Lazarus RA. Selection and characterization of a new class of peptide exosite inhibitors of coagulation factor VIIa. Biochemistry 2001; 40: 951321.
  • 34
    Roberge M, Santell L, Dennis MS, Eigenbrot C, Dwyer MA, Lazarus RA. A novel exosite on coagulation factor VIIa and its molecular interactions with a new class of peptide inhibitors. Biochemistry 2001; 40: 952231.
  • 35
    Roberge M, Peek M, Kirchhofer D, Dennis MS, Lazarus RA. Fusion of two distinct peptide exosite inhibitors of Factor VIIa. Biochem J 2002; 363: 38793.
  • 36
    Maun HR, Eigenbrot C, Lazarus RA. Engineering exosite peptides for complete inhibition of factor VIIa using a protease switch with substrate phage. J Biol Chem 2003; 278: 2182330.
  • 37
    Sorensen BB, Persson E, Freskgard PO, Kjalke M, Ezban M, Williams T, Rao LV. Incorporation of an active site inhibitor in factor VIIa alters the affinity for tissue factor. J Biol Chem 1997; 272: 118638.
  • 38
    Uchiba M, Okajima K, Abe H, Okabe H, Takatsuki K. Effect of nafamostat mesilate, a synthetic protease inhibitor, on tissue factor-factor VIIa complex activity. Thromb Res 1994; 74: 15561.
  • 39
    Lazarus RA, Olivero AG, Eigenbrot C, Kirchhofer D. Inhibitors of tissue factor. Factor VIIa for anticoagulant therapy. Curr Med Chem 2004; 11: 227590.
  • 40
    Olivero AG, Eigenbrot C, Goldsmith R, Robarge K, Artis DR, Flygare J, Rawson T, Sutherlin DP, Kadkhodayan S, Beresini M, Elliott LO, DeGuzman GG, Banner DW, Ultsch M, Marzec U, Hanson SR, Refino C, Bunting S, Kirchhofer D. A selective, slow binding inhibitor of factor VIIa binds to a nonstandard active site conformation and attenuates thrombus formation in vivo. J Biol Chem 2005; 280: 91609.
  • 41
    Buckman BO, Chou YL, McCarrick M, Liang A, Lentz D, Mohan R, Morrissey MM, Shaw KJ, Trinh L, Light DR. Solid-phase synthesis of naphthylamidines as factor VIIa/tissue factor inhibitors. Bioorg Med Chem Lett 2005; 15: 224952.
  • 42
    Suleymanov OD, Szalony JA, Salyers AK, LaChance RM, Parlow JJ, South MS, Wood RS, Nicholson NS. Pharmacological interruption of acute thrombus formation with minimal hemorrhagic complications by a small molecule tissue factor/factor VIIa inhibitor: comparison to factor Xa and thrombin inhibition in a nonhuman primate thrombosis model. J Pharmacol Exp Ther 2003; 306: 111521.
  • 43
    Szalony JA, Suleymanov OD, Salyers AK, Panzer-Knodle SG, Blom JD, LaChance RM, Case BL, Parlow JJ, South MS, Wood RS, Nicholson NS. Administration of a small molecule tissue factor/factor VIIa inhibitor in a non-human primate thrombosis model of venous thrombosis: effects on thrombus formation and bleeding time. Thromb Res 2003; 112: 16774.
  • 44
    Young WB, Mordenti J, Torkelson S, Shrader WD, Kolesnikov A, Rai R, Liu L, Hu H, Leahy EM, Green MJ, Sprengeler PA, Katz BA, Yu C, Janc JW, Elrod KC, Marzec UM, Hanson SR. Factor VIIa inhibitors: chemical optimization, preclinical pharmacokinetics, pharmacodynamics, and efficacy in an arterial baboon thrombosis model. Bioorg Med Chem Lett 2006; 16: 203741.
  • 45
    Arnold CS, Parker C, Upshaw R, Prydz H, Chand P, Kotian P, Bantia S, Babu YS. The antithrombotic and anti-inflammatory effects of BCX-3607, a small molecule tissue factor/factor VIIa inhibitor. Thromb Res 2006; 117: 3439.
  • 46
    Banerjee Y, Mizuguchi J, Iwanaga S, Kini RM. Hemextin AB complex – a snake venom anticoagulant protein complex that inhibits factor VIIa activity. Pathophysiol Haemost Thromb 2005; 34: 1847.
  • 47
    Kelley RF, Refino CJ, O'Connell MP, Modi N, Sehl P, Lowe D, Pater C, Bunting S. A soluble tissue factor mutant is a selective anticoagulant and antithrombotic agent. Blood 1997; 89: 321927.
  • 48
    Himber J, Refino CJ, Burcklen L, Roux S, Kirchhofer D. Inhibition of arterial thrombosis by a soluble tissue factor mutant and active site-blocked factors IXa and Xa in the guinea pig. Thromb Haemost 2001; 85: 47581.
  • 49
    Yang J, Lee GF, Riederer MA, Kelley RF. Enhancing the anticoagulant potency of soluble tissue factor mutants by increasing their affinity to factor VIIa. Thromb Haemost 2002; 87: 4508.
  • 50
    Kirchhofer D, Moran P, Chiang N, Kim J, Riederer MA, Eigenbrot C, Kelley RF. Epitope location on tissue factor determines the anticoagulant potency of monoclonal anti-tissue factor antibodies. Thromb Haemost 2000; 84: 107281.
  • 51
    Levi M, ten Cate H, Bauer KA, van der Poll T, Edgington TS, Buller HR, van Deventer SJ, Hack CE, ten Cate JW, Rosenberg RD. Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 1994; 93: 11420.
  • 52
    Huang H, Norledge BV, Liu C, Olson AJ, Edgington TS. Selective attenuation of the extrinsic limb of the tissue factor-driven coagulation protease cascade by occupancy of a novel peptidyl docking site on tissue factor. Biochemistry 2003; 42: 1061926.
  • 53
    Biemond BJ, Levi M, ten Cate H, Soule HR, Morris LD, Foster DL, Bogowitz CA, van der Poll T, Buller HR, ten Cate JW. Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa. Thromb Haemost 1995; 73: 22330.
  • 54
    Jiao JA, Kelly AB, Marzec UM, Nieves E, Acevedo J, Burkhardt M, Edwards A, Zhu XY, Chavaillaz PA, Wong A, Wong JL, Egan JO, Taylor D, Rhode PR, Wong HC. Inhibition of acute vascular thrombosis in chimpanzees by an anti-human tissue factor antibody targeting the factor X binding site. Thromb Haemost 2010; 103: 22433.
  • 55
    Morrow DA, Murphy SA, McCabe CH, Mackman N, Wong HC, Antman EM. Potent inhibition of thrombin with a monoclonal antibody against tissue factor (Sunol-cH36): results of the PROXIMATE-TIMI 27 trial. Eur Heart J 2005; 26: 6828.
  • 56
    Lee A, Agnelli G, Buller H, Ginsberg J, Heit J, Rote W, Vlasuk G, Costantini L, Julian J, Comp P, van Der Meer J, Piovella F, Raskob G, Gent M. Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation 2001; 104: 748.
  • 57
    Moons AH, Peters RJ, Bijsterveld NR, Piek JJ, Prins MH, Vlasuk GP, Rote WE, Buller HR. Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty. J Am Coll Cardiol 2003; 41: 214753.
  • 58
    Mueller BM, Reisfeld RA, Edgington TS, Ruf W. Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci U S A 1992; 89: 118326.
  • 59
    Hembrough TA, Swartz GM, Papathanassiu A, Vlasuk GP, Rote WE, Green SJ, Pribluda VS. Tissue factor/factor VIIa inhibitors block angiogenesis and tumor growth through a nonhemostatic mechanism. Cancer Res 2003; 63: 29973000.