Tissue factor and thrombosis: The clot starts here

 

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Summary

Thrombosis, or complications from thrombosis, currently occupies the top three positions in the cardiovascular causes of morbidity and mortality in the developed world. There are a limited number of safe and effective drugs to prevent and treat thrombosis. Animal models of thrombosis are necessary to better understand the complex components and interactions involved in the formation of a clot. Tissue factor (TF) is required for the initiation of blood coagulation and likely plays a key role in both arterial and venous thrombosis. Understanding the role of TF in thrombosis may permit the development of new antithrombotic drugs. This review will focus on the role of TF in in vivo models of thrombosis.

• References

• 1 Edgington TS, Mackman N, Brand K. et al. The structural biology of expression and function of tissue factor. Thromb Haemost 1991; 66: 67-79.
  Article in Thieme ConnectPubMedGoogle Scholar
• 2 Bach RR. Initiation of coagulation by tissue factor. CRC Crit Rev Biochem 1988; 23: 339-368.
  PubMedGoogle Scholar
• 3 Broze Jr. GJ. Tissue factor pathway inhibitor and the current concept of blood coagulation. Blood Coagul Fibrinolysis 1995; 6 (Suppl. 01) S7-S13.
  CrossrefPubMedGoogle Scholar
• 4 Drake TA, Morrissey JH, Edgington TS. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol 1989; 134: 1087-1097.
  PubMedGoogle Scholar
• 5 Fleck RA, Rao LV, Rapaport SI. et al. Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody. Thromb Res 1990; 59: 421-437.
  CrossrefPubMedGoogle Scholar
• 6 Flossel C, Luther T, Muller M, Albrecht S, Kasper M. Immunohistochemical detection of tissue factor (TF) on paraffin sections of routinely fixed human tissue. Histochemistry 1994; 101: 449-453.
  CrossrefPubMedGoogle Scholar
• 7 Rauch U, Nemerson Y. Circulating tissue factor and thrombosis. Curr Opin Hematol 2000; 7: 273-277.
  CrossrefPubMedGoogle Scholar
• 8 Butenas S, Bouchard BA, Brummel-Ziedins KE. et al. Tissue factor activity in whole blood. Blood 2005; 105: 2764-2770.
  CrossrefPubMedGoogle Scholar
• 9 Day SM, Reeve JL, Pedersen B. et al. Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood 2005; 105: 192-198.
  CrossrefPubMedGoogle Scholar
• 10 Diamant M, Nieuwland R, Pablo RF. et al. Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus. Circulation 2002; 106: 2442-2447.
  CrossrefPubMedGoogle Scholar
• 11 Giesen PL, Rauch U, Bohrmann B. et al. Blood-borne tissue factor: another view of thrombosis. Proc Natl Acad Sci USA 1999; 96: 2311-2315.
  CrossrefPubMedGoogle Scholar
• 12 Siddiqui FA, Desai H, Amirkhosravi A. et al. The presence and release of tissue factor from human platelets. Platelets 2002; 13: 247-253.
  CrossrefPubMedGoogle Scholar
• 13 So AK, Varisco PA, Kemkes-Matthes B. et al. Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways. J Thromb Haemost 2003; 1: 2510-2515.
  CrossrefPubMedGoogle Scholar
• 14 Egorina EM, Sovershaev MA, Bjorkoy G. et al. Intracellular and surface distribution of monocyte tissue factor: application to intersubject variability. Arterioscler Thromb Vasc Biol 2005; 25: 1493-1498.
  CrossrefPubMedGoogle Scholar
• 15 Morel O, Toti F, Hugel B, Bakouboula B, Camoin-Jau L, Dignat-George F. et al. Procoagulant microparticles: disrupting the vascular homeostasis equation?. Arterioscler Thromb Vasc Biol 2006; 26: 2594-2604.
  CrossrefPubMedGoogle Scholar
• 16 Boden G, Rao AK. Effects of hyperglycemia and hyperinsulinemia on the tissue factor pathway of blood coagulation. Curr Diab Rep 2007; 7: 223-227.
  CrossrefPubMedGoogle Scholar
• 17 Moosbauer C, Morgenstern E, Cuvelier SL. et al. Eosinophils are a major intravascular location for tissue factor storage and exposure. Blood 2007; 109: 995-1002.
  PubMedGoogle Scholar
• 18 Pawlinski R, Pedersen B, Erlich J. et al. Role of tissue factor in haemostasis, thrombosis, angiogenesis and inflammation: lessons from low tissue factor mice. Thromb Haemost 2004; 92: 444-450.
  Article in Thieme ConnectPubMedGoogle Scholar
• 19 Soejima H, Ogawa H, Yasue H. et al. Heightened tissue factor associated with tissue factor pathway inhibitor and prognosis in patients with unstable angina. Circulation 1999; 99: 2908-2913.
  CrossrefPubMedGoogle Scholar
• 20 Kakkar AK, DeRuvo N, Chinswangwatanakul V. et al. Extrinsic-pathway activation in cancer with high factor VIIa and tissue factor. Lancet 1995; 346: 1004-1005.
  CrossrefPubMedGoogle Scholar
• 21 Sturk-Maquelin KN, Nieuwland R, Romijn FP. et al. Pro- and non-coagulant forms of non-cell-bound tissue factor in vivo. J Thromb Haemost 2003; 1: 1920-1926.
  CrossrefPubMedGoogle Scholar
• 22 Aras O, Shet A, Bach RR. et al. Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. Blood 2004; 103: 4545-4553.
  CrossrefPubMedGoogle Scholar
• 23 Marsik C, Quehenberger P, Mackman N. et al. Validation of a novel tissue factor assay in experimental human endotoxemia. Thromb Res 2003; 111: 311-315.
  CrossrefPubMedGoogle Scholar
• 24 Key NS, Slungaard A, Dandelet L. et al. Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease. Blood 1998; 91: 4216-4223.
  PubMedGoogle Scholar
• 25 Toomey JR, Kratzer KE, Lasky NM. et al. Targeted disruption of the murine tissue factor gene results in embryonic lethality. Blood 1996; 88: 1583-1587.
  PubMedGoogle Scholar
• 26 Carmeliet P, Mackman N, Moons L. et al. Role of tissue factor in embryonic blood vessel development. Nature 1996; 383: 73-75.
  CrossrefPubMedGoogle Scholar
• 27 Bugge TH, Xiao Q, Kombrinck KW, Flick MJ, Holmback K, Danton MJ. et al. Fatal embryonic bleeding events in mice lacking tissue factor, the cell-associated initiator of blood coagulation. Proc Natl Acad Sci USA 1996; 93: 6258-6263.
  CrossrefPubMedGoogle Scholar
• 28 Parry GC, Erlich JH, Carmeliet P. et al. Low levels of tissue factor are compatible with development and hemostasis in mice. J Clin Invest 1998; 101: 560-569.
  CrossrefPubMedGoogle Scholar
• 29 Pan S, Kleppe LS, Witt TA. et al. The effect of vascular smooth muscle cell-targeted expression of tissue factor pathway inhibitor in a murine model of arterial thrombosis. Thromb Haemost 2004; 92: 495-502.
  Article in Thieme ConnectPubMedGoogle Scholar
• 30 Marmur JD, Thiruvikraman SV, Fyfe BS. et al. Identification of active tissue factor in human coronary atheroma. Circulation 1996; 94: 1226-1232.
  CrossrefPubMedGoogle Scholar
• 31 Tremoli E, Camera M, Toschi V. et al. Tissue factor in atherosclerosis. Atherosclerosis 1999; 144: 273-283.
  CrossrefPubMedGoogle Scholar
• 32 Wilcox JN, Smith KM, Schwartz SM. et al. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 1989; 86: 2839-2843.
  CrossrefPubMedGoogle Scholar
• 33 Misumi K, Ogawa H, Yasue H. et al. Comparison of plasma tissue factor levels in unstable and stable angina pectoris. Am J Cardiol 1998; 81: 22-26.
  CrossrefPubMedGoogle Scholar
• 34 Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol 2004; 24: 1015-1022.
  CrossrefPubMedGoogle Scholar
• 35 Sturgeon SA, Jones C, Angus JA, Wright CE. Adaptation of the Folts and electrolytic methods of arterial thrombosis for the study of anti-thrombotic molecules in small animals. J Pharmacol Toxicol Methods 2006; 53: 20-29.
  CrossrefPubMedGoogle Scholar
• 36 Speidel CM, Thornton JD, Meng YY. et al. Procoagulant activity on injured arteries and associated thrombi is mediated primarily by the complex of tissue factor and factor VIIa. Coron Artery Dis 1996; 7: 57-62.
  PubMedGoogle Scholar
• 37 Pawashe AB, Golino P, Ambrosio G. et al. A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in stenotic injured rabbit carotid arteries. Circ Res 1994; 74: 56-63.
  CrossrefPubMedGoogle Scholar
• 38 Suleymanov OD, Szalony JA, Salyers AK. et al. 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: 1115-1121.
  CrossrefPubMedGoogle Scholar
• 39 Abendschein DR, Baum PK, Verhallen P. et al. A novel synthetic inhibitor of factor Xa decreases early reocclusion and improves 24-h patency after coronary fibrinolysis in dogs. J Pharmacol Exp Ther 2001; 296: 567-572.
  PubMedGoogle Scholar
• 40 Lefkovits J, Malycky JL, Rao JS. et al. Selective inhibition of factor Xa is more efficient than factor VIIa-tissue factor complex blockade at facilitating coronary thrombolysis in the canine model. J Am Coll Cardiol 1996; 28: 1858-1865.
  CrossrefPubMedGoogle Scholar
• 41 Carmeliet P, Moons L, Collen D. Mouse models of angiogenesis, arterial stenosis, atherosclerosis and hemostasis. Cardiovasc Res 1998; 39: 8-33.
  CrossrefPubMedGoogle Scholar
• 42 Asada Y, Hara S, Tsuneyoshi A. et al. 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: 506-511.
  Article in Thieme ConnectPubMedGoogle Scholar
• 43 Roque M, Reis ED, Fuster V. et al. Inhibition of tissue factor reduces thrombus formation and intimal hyperplasia after porcine coronary angioplasty. J Am Coll Cardiol 2000; 36: 2303-2310.
  CrossrefPubMedGoogle Scholar
• 44 Chi L, Gibson G, Peng YW. et al. Characterization of a tissue factor/factor VIIa-dependent model of thrombosis in hypercholesterolemic rabbits. J Thromb Haemost 2004; 2: 85-92.
  CrossrefPubMedGoogle Scholar
• 45 Tseng MT, Dozier A, Haribabu B. et al. Transendothelial migration of ferric ion in FeCl3 injured murine common carotid artery. Thromb Res 2006; 118: 275-280.
  CrossrefPubMedGoogle Scholar
• 46 Farrehi PM, Ozaki CK, Carmeliet P. et al. Regulation of arterial thrombolysis by plasminogen activator inhibitor-1 in mice. Circulation 1998; 97: 1002-1008.
  CrossrefPubMedGoogle Scholar
• 47 Wang L, Miller C, Swarthout RF. et al. Vascular smooth muscle-derived tissue factor is critical for arterial thrombosis after ferric chloride-induced injury. Blood 2009; 113: 705-713.
  CrossrefPubMedGoogle Scholar
• 48 Ambrosio G, Tritto I, Golino P. Reactive oxygen metabolites and arterial thrombosis. Cardiovasc Res 1997; 34: 445-452.
  CrossrefPubMedGoogle Scholar
• 49 Wilson CA, Hatchell DL. Photodynamic retinal vascular thrombosis. Rate and duration of vascular occlusion. Invest Ophthalmol Vis Sci 1991; 32: 2357-2365.
  PubMedGoogle Scholar
• 50 Westrick RJ, Bodary PF, Xu Z. et al. Deficiency of tissue factor pathway inhibitor promotes atherosclerosis and thrombosis in mice. Circulation 2001; 103: 3044-3046.
  CrossrefPubMedGoogle Scholar
• 51 Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008; 451: 914-918.
  CrossrefPubMedGoogle Scholar
• 52 Eppihimer MJ, Schaub RG. P-Selectin-dependent inhibition of thrombosis during venous stasis. Arterioscler Thromb Vasc Biol 2000; 20: 2483-2488.
  CrossrefPubMedGoogle Scholar
• 53 Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol 2007; 44: 62-69.
  CrossrefPubMedGoogle Scholar
• 54 Urbach D, Matzen KA, Heitmann D. et al. Relation between peri-operative anti-thrombin activity and deep vein thrombosis after elective hip replacement surgery. Vasa 2003; 32: 14-17.
  CrossrefPubMedGoogle Scholar
• 55 Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins. J Clin Pathol 1974; 27: 517-528.
  CrossrefPubMedGoogle Scholar
• 56 Hron G, Kollars M, Weber H. et al. Tissue factor-positive microparticles: cellular origin and association with coagulation activation in patients with colorectal cancer. Thromb Haemost 2007; 97: 119-123.
  Article in Thieme ConnectPubMedGoogle Scholar
• 57 Polgar J, Matuskova J, Wagner DD. The P-selectin, tissue factor, coagulation triad. J Thromb Haemost 2005; 3: 1590-1596.
  CrossrefPubMedGoogle Scholar
• 58 Johnson GJ, Leis LA, Bach RR. Tissue factor activity of blood mononuclear cells is increased after total knee arthroplasty. Thromb Haemost 2009; 102: 728-734.
  Article in Thieme ConnectPubMedGoogle Scholar
• 59 Himber J, Kling D, Fallon JT, Nemerson Y, Riederer MA. In situ localization of tissue factor in human thrombi. Blood 2002; 99: 4249-4250.
  CrossrefPubMedGoogle Scholar
• 60 Kamikura Y, Wada H, Nobori T. et al. Elevated levels of leukocyte tissue factor mRNA in patients with venous thromboembolism. Thromb Res 2005; 116: 307-312.
  CrossrefPubMedGoogle Scholar
• 61 Holschermann H, Haberbosch W, Terhalle HM. et al. Increased monocyte tissue factor activity in women following cerebral venous thrombosis. J Neurol 2003; 250: 631-632.
  CrossrefPubMedGoogle Scholar
• 62 Lee A, Agnelli G, Buller H. et al. 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: 74-78.
  CrossrefPubMedGoogle Scholar
• 63 Reyers I, Mussoni L, Donati MB. et al. Failure of aspirin at different doses to modify experimental thrombosis in rats. Thromb Res 1980; 18: 669-674.
  CrossrefPubMedGoogle Scholar
• 64 Wakefield TW, Strieter RM, Wilke CA. et al. Venous thrombosis-associated inflammation and attenuation with neutralizing antibodies to cytokines and adhesion molecules. Arterioscler Thromb Vasc Biol 1995; 15: 258-268.
  CrossrefPubMedGoogle Scholar
• 65 Zhou J, May L, Liao P. et al. Inferior vena cava ligation rapidly induces tissue factor expression and venous thrombosis in rats. Arterioscler Thromb Vasc Biol 2009; 29: 863-869.
  CrossrefPubMedGoogle Scholar
• 66 Szalony JA, Suleymanov OD, Salyers AK. et al. 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: 167-174.
  CrossrefPubMedGoogle Scholar
• 67 Biro E, Sturk-Maquelin KN, Vogel GM. et al. Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost 2003; 1: 2561-2568.
  CrossrefPubMedGoogle Scholar
• 68 Himber J, Wohlgensinger C, Roux S. et al. Inhibition of tissue factor limits the growth of venous thrombus in the rabbit. J Thromb Haemost 2003; 1: 889-895.
  CrossrefPubMedGoogle Scholar
• 69 McGuinness CL, Humphries J, Waltham M. et al. Recruitment of labelled monocytes by experimental venous thrombi. Thromb Haemost 2001; 85: 1018-1024.
  Article in Thieme ConnectPubMedGoogle Scholar
• 70 Koellnberger M, von Bruehl M, Bergmeier W. et al. Platelets Contribute to Arterial and Venous Thrombosis in vivo [Abstract]. Circulation 2007; 116 (Suppl. 16) II_75 Abstract: 448.
  PubMedGoogle Scholar
• 71 Rosen ED, Raymond S, Zollman A. et al. Laser-induced noninvasive vascular injury models in mice generate platelet- and coagulation-dependent thrombi. Am J Pathol 2001; 158: 1613-1622.
  CrossrefPubMedGoogle Scholar
• 72 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.
  CrossrefPubMedGoogle Scholar
• 73 Falati S, Gross P, Merrill-Skoloff G. et al. Real-time in vivo imaging of platelets, tissue factor and fibrin during arterial thrombus formation in the mouse. Nat Med 2002; 8: 1175-1181.
  CrossrefPubMedGoogle Scholar
• 74 Chou J, Mackman N, Merrill-Skoloff G. et al. Hematopoietic cell-derived micro-particle tissue factor contributes to fibrin formation during thrombus propagation. Blood 2004; 104: 3190-3197.
  CrossrefPubMedGoogle Scholar
• 75 Gross PL, Furie BC, Merrill-Skoloff G. et al. Leukocyte-versus microparticle-mediated tissue factor transfer during arteriolar thrombus development. J Leukoc Biol 2005; 78: 1318-1326.
  CrossrefPubMedGoogle Scholar
• 76 Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med 1999; 341: 586-592.
  CrossrefPubMedGoogle Scholar
• 77 Levi M, de Jonge E, van der Poll T. et al. Disseminated intravascular coagulation. Thromb Haemost 1999; 82: 695-705.
  Article in Thieme ConnectPubMedGoogle Scholar
• 78 Baglin T. Disseminated intravascular coagulation: diagnosis and treatment. Br Med J 1996; 312: 683-687.
  CrossrefPubMedGoogle Scholar
• 79 Levi M. Disseminated intravascular coagulation: What’s new?. Crit Care Clin 2005; 21: 449-467.
  CrossrefPubMedGoogle Scholar
• 80 Levi M, van der Poll T, ten Cate H. et al. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia. Eur J Clin Invest 1997; 27: 3-9.
  PubMedGoogle Scholar
• 81 Gando S. Disseminated intravascular coagulation in trauma patients. Semin Thromb Hemost 2001; 27: 585-592.
  Article in Thieme ConnectPubMedGoogle Scholar
• 82 van Deventer SJ, Buller HR, ten Cate JW. et al. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 1990; 76: 2520-2526.
  CrossrefPubMedGoogle Scholar
• 83 van der Poll T, Buller HR, ten Cate H. et al. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990; 322: 1622-1627.
  CrossrefPubMedGoogle Scholar
• 84 Pixley RA, De La Cadena R, Page JD. et al. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia. In vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J Clin Invest 1993; 91: 61-68.
  CrossrefPubMedGoogle Scholar
• 85 Shimura M, Wada H, Wakita Y. et al. Plasma tissue factor and tissue factor pathway inhibitor levels in patients with disseminated intravascular coagulation. Am J Hematol 1996; 52: 165-170.
  CrossrefPubMedGoogle Scholar
• 86 Drake TA, Cheng J, Chang A. et al. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993; 142: 1458-1470.
  PubMedGoogle Scholar
• 87 Taylor Jr FB, Chang A, Ruf W. et al. Lethal E coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-134.
  PubMedGoogle Scholar
• 88 Carr C, Bild GS, Chang AC. et al. Recombinant E coli-derived tissue factor pathway inhibitor reduces coagulopathic and lethal effects in the baboon gram-negative model of septic shock. Circ Shock 1994; 44: 126-137.
  PubMedGoogle Scholar
• 89 Taylor FB, Chang AC, Peer G. et al. Active site inhibited factor VIIa (DEGR VIIa) attenuates the coagulant and interleukin-6 and –8, but not tumor necrosis factor, responses of the baboon to LD100 Escherichia coli. Blood 1998; 91: 1609-1615.
  PubMedGoogle Scholar
• 90 Levi M, ten Cate H, Bauer KA. et al. 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: 114-120.
  CrossrefPubMedGoogle Scholar
• 91 Biemond BJ, Levi M, ten Cate H. et al. Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monoclonal Fab fragment against factor VII/VIIa. Thromb Haemost 1995; 73: 223-230.
  Article in Thieme ConnectPubMedGoogle Scholar
• 92 Warr TA, Rao LV, Rapaport SI. Disseminated intravascular coagulation in rabbits induced by administration of endotoxin or tissue factor: effect of anti-tissue factor antibodies and measurement of plasma extrinsic pathway inhibitor activity. Blood 1990; 75: 1481-1489.
  PubMedGoogle Scholar
• 93 Pawlinski R, Pedersen B, Schabbauer G. et al. Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia. Blood 2004; 103: 1342-1347.
  PubMedGoogle Scholar
• 94 Pawlinski R, Mackman N. Cellular sources of tissue factor that contribute to activation of coagulation in endotoxemic mice. J Thromb Haemost. 2009 7 (Suppl 2): Abstract AS-MO-042.
  PubMedGoogle Scholar