Pharmacological Inhibition of Tissue Factor

ABSTRACT

Tissue factor plays an essential role in the initiation of coagulation in vivo. In severe conditions, including sepsis and acute lung injury, increased expression of tissue factor may induce disseminated intravascular coagulation and fibrin deposition in organs, which are believed to have a determining impact on patient outcome. Tissue factor also acts as a signaling receptor and is involved in the systemic inflammatory response, as in cancer progression and atherosclerosis. Interventions aiming at limiting tissue factor activities have been evaluated in multiple experimental studies and the observed results have supported the potential benefits for coagulation disorders, inflammation, and survival. The effects of the main physiological inhibitor of tissue factor, tissue factor pathway inhibitor, have been evaluated in two large clinical trials in sepsis. Even though they are not associated with an improved outcome, the observed data support further clinical studies.

KEYWORDS

Tissue factor - sepsis - animal models - tissue factor pathway inhibitor (TFPI) - SIRS - DIC

REFERENCES

• 1 Lupu C, Westmuckett A D, Peer G et al.. Tissue factor-dependent coagulation is preferentially up-regulated within arterial branching areas in a baboon model of Escherichia coli sepsis.  Am J Pathol. 2005;  167 1161-1172
• 2 Morrissey J H. Tissue factor: an enzyme cofactor and a true receptor.  Thromb Haemost. 2001;  86 66-74
• 3 Marmur J D, Thiruvikraman S V, Fyfe B S et al.. Identification of active tissue factor in human atherosclerotic plaques in human coronary atheroma.  Circulation. 1996;  94 1226-1232
• 4 Callander N S, Varki N, Rao L V. Immunohistochemical identification of tissue factor in solid tumors.  Cancer. 1992;  70 1194-1201
• 5 Ryan J, Brett J, Tijburg P et al.. Tumor necrosis factor-induced endothelial tissue factor is associated with subendothelial matrix vesicles but is not expressed on the apical surface.  Blood. 1992;  80 966-974
• 6 Rivers R P, Hathaway W E, Weston W L. The endotoxin-induced coagulant activity of human monocytes.  Br J Haematol. 1975;  30 311-316
• 7 van der Poll T, de Jonge E, Levi M et al.. Pathogenesis of DIC in sepsis.  Sepsis. 1999;  3 103-109
• 8 Levi M, de Jonge E, van der Poll T et al.. Disseminated intravascular coagulation.  Thromb Haemost. 1999;  82 695-705
• 9 Sevinsky J R, Rao L V, 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;  133 293-304
• 10 Bajaj M S, Bajaj S P. Tissue factor pathway inhibitor: potential therapeutic applications.  Thromb Haemost. 1997;  78 471-477
• 11 Gando S, Kameue T, Matsuda N et al.. Imbalances between the levels of tissue factor and tissue factor pathway inhibitor in ARDS patients.  Thromb Res. 2003;  109 119-124
• 12 Gando S, Kameue T, Morimoto Y et al.. Tissue factor production not balanced by tissue factor pathway inhibitor in sepsis promotes poor prognosis.  Crit Care Med. 2002;  30 1729-1734
• 13 Park C T, Creasey A A, Wright S. Tissue factor pathway inhibitor blocks cellular effects of endotoxin by binding to endotoxin and interfering with transfer to CD14.  Blood. 1997;  89 4268-4274
• 14 Riewald M, Ruf W. Mechanistic coupling of protease signaling and initiation of coagulation by tissue factor.  Proc Natl Acad Sci USA. 2001;  98 7742-7747
• 15 Warr T A, Rao L V, Rapaport S I. 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
• 16 Levi M, ten Cate H, Bauer K A 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
• 17 Taylor Jr F B, 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
• 18 Creasey A A, Chang A CK, Feigen L et al.. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock.  J Clin Invest. 1993;  91 2850-2860
• 19 Carr C, Bild G S, Chang A C 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
• 20 Enkhbaatar P, Okajima K, Murakami K et al.. Recombinant tissue factor pathway inhibitor reduces lipopolysaccharide-induced pulmonary vascular injury by inhibiting leukocyte activation.  Am J Respir Crit Care Med. 2000;  162 1752-1759
• 21 Opal S, Palardy J E, Parejo N A, Creasey A A. The activity of tissue factor pathway inhibitor in experimental models of superantigen-induced shock and polymicrobial intra-abdominal sepsis.  Crit Care Med. 2001;  29 13-17
• 22 Welty-Wolf K E, Carraway M S, Miller D L et al.. Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons.  Am J Respir Crit Care Med. 2001;  164 1988-1996
• 23 Miller D L, Welty-Wolf K, Carraway M S et al.. Extrinsic coagulation blockade attenuates lung injury and proinflammatory cytokine release after intratracheal lipopolysaccharide.  Am J Respir Cell Mol Biol. 2002;  26 650-658
• 24 de Jonge E, Dekkers P E, Creasey A A et al.. Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia.  Blood. 2000;  95 1124-1129
• 25 de Jonge E, Dekkers P E, Creasey A A et al.. Tissue factor pathway inhibitor does not influence inflammatory pathways during human endotoxemia.  J Infect Dis. 2001;  183 1815-1818
• 26 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, randomised, placebo-controlled, single-blind, dose escalation study.  Crit Care Med. 2001;  29 2081-2089
• 27 Abraham E, Reinhart K, Opal S et al.. Efficacy and safety of Tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis.  JAMA. 2003;  290 238-247
• 28 Enjyoji K, Miyata T, Kamikubo Y, Kato H. Effect of heparin on the inhibition of factor Xa by tissue factor pathway inhibitor: a segment, Gly212-Phe243, of the third Kunitz domain is a heparin-binding site.  Biochemistry. 1995;  34 5725-5735
• 29 Opal S, Wunderink R, Laterre P F et al.. Therapeutic rationale for tissue factor pathway inhibitor for severe community-acquired pneumonia (CAP (abstract 234). In: Final program and abstracts of 42nd Annual Meeting Infections Disease Society of America September 30-October 3, 2004 Boston, MA;