The coagulation cascade in sepsis

Current Pharmaceutical Design

Volumn 14, Issue 19, 2008, Pages 1860-1869

  Wang, Ling ^a   Bastarache, Julie A ^a   Ware, Lorraine B ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NONE   (United States)

Author keywords

Activated protein C; Coagulation; Fibrinolysis; Inflammation; Pathogenesis; Sepsis; Tissue factor (TF)

Indexed keywords

ACTIVATED PROTEIN C; ALTEPLASE; ANTICOAGULANT AGENT; ANTITHROMBIN III; BLOOD CLOTTING FACTOR 7A; CORTICOSTEROID; DROTRECOGIN; FIBRIN; HEPARIN; HEPARIN DERIVATIVE; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; LOW MOLECULAR WEIGHT HEPARIN; PLACEBO; PLASMINOGEN ACTIVATOR INHIBITOR; PROTEIN C; PROTEIN S; RECOMBINANT THROMBOMODULIN; RECOMBINANT TISSUE FACTOR PATHWAY INHIBITOR; THROMBOMODULIN; THROMBOPLASTIN; TISSUE FACTOR PATHWAY INHIBITOR; TISSUE PLASMINOGEN ACTIVATOR; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UROKINASE;

ANTICOAGULANT THERAPY; ANTICOAGULATION; ANTIINFLAMMATORY ACTIVITY; BLEEDING; BLOOD CLOTTING; CLINICAL TRIAL; CONTINUOUS INFUSION; DISSEMINATED INTRAVASCULAR CLOTTING; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG TARGETING; FIBRINOLYSIS; HUMAN; INFLAMMATION; LOW DRUG DOSE; MORTALITY; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SEPSIS; SEPTIC SHOCK; SURVIVAL RATE;

ANIMALS; BLOOD COAGULATION; DRUG DELIVERY SYSTEMS; FIBRIN; FIBRINOLYSIS; HUMANS; PLASMINOGEN ACTIVATOR INHIBITOR 1; PROTEIN C; RECOMBINANT PROTEINS; SEPSIS; THROMBOPLASTIN;

EID: 48249085676     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161208784980581     Document Type: Review

References (126)

1. Danai P, Martin GS. Epidemiology of sepsis: Recent advances. Curr Infect Dis Rep 2005; 7(5): 329-34.
2. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001; 29(7): 1303-10.
3. Warren HS. Strategies for the treatment of sepsis. N Engl J Med 1997; 336(13): 952-3.
4. Bone RC, Fisher CJ Jr, Clemmer TP, Slotman GJ, Metz CA, Balk RA. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987; 317(11): 653-8.
5. Group VASSCS. Effect of high-dose glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. The Veterans Administration Systemic Sepsis Cooperative Study Group. N Engl J Med 1987; 317(11): 659-65.
6. Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, et al. Corticosteroid treatment for sepsis: A critical appraisal and meta-analysis of the literature. Crit Care Med 1995; 23(8): 1430-9.
7. Ziegler EJ, Fisher CJ Jr, Sprung CL, Straube RC, Sadoff JC, Foulke GE, et al. Treatment of gram-negatiye bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med 1991; 324(7): 429-36.
8. Fisher CJ Jr, Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, et al. Treatment of septic shock with the tumor necrosis factor receptor: Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med 1996; 334(26): 1697-702.
9. Fisher CJ Jr, Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. Jama 1994; 271(23): 1836-43.
10. Bastarache JA, Ware LB, Bernard GR. The role of the coagulation cascade in the continuum of sepsis and acute lung injury and acute respiratory distress syndrome. Semin Respir Crit Care Med 2006; 27(4): 365-76.
11. Esmon CT. Coagulation and inflammation. J Endotoxin Res 2003; 9(3): 192-8.
12. Bernard, GR, Vincent JL, Latérre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344(10): 699-709.
13. Idell S. Extravascular coagulation and fibrin deposition in acute lung injury. New Horiz 1994; 2(4): 566-74.
14. Dixon B. The role of microvascular thrombosis in sepsis. Anaesth Intensive Care 2004; 32(5): 619-29.
15. Levi M. Current understariding of disseminated intravascular coagulation. Br J Haematol 2004; 124(5): 567-76.
16. Welty-Wolf KE, Carraway MS, Miller DL, Ortel TL, Ezban M, Ghio AJ, et al. Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons. Am J Respit Crit Care Med 2001; 164(10 Pt 1): 1988-96.
17. Esmon CT, Fukudome K, Mather T, Bode W, Regan LM, Stearns-Kurosawa DJ, et al. Inflammation, sepsis, and coagulation. Haematologica 1999; 84(3):254-9.
18. Hack CE. Tissue factor pathway of coagulation in sepsis. Crit Care Med 2000; 28(9 Suppl): S25-30.
19. Taylor FB Jr, Chang A, Ruf W, Morrissey JH, Hinshaw L, Catlett R, et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33(3): 127-34.
20. Taylor FB, Chang AC, Peer G, Li A, Ezban M, Hedner U. 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 LD 100 Escherichia coli. Blood 1998; 91(5): 1609-15.
21. Napoleone E, Di Santo A, Lorenzet R. Monocytes upregulate endothelial cell expression of tissue factor: A role for cell-cell contact and cross-talk. Blood 1997; 89(2): 541-9.
22. Bastarache JA, Wang L, Geiser T, Wang Z, Albertine KH, Matthay MA, et al. The alveolar epithelium can initiate the extrinsic coagulation cascade through expression of tissue factor. Thorax 2007; 62(7): 608-16.
23. Drake TA, Cheng J, Chang A, Taylor FB, Jr. Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. Am J Pathol 1993; 142(5): 1458-70.
24. Lupu C, Westmuckett AD, Peer G, Ivanciu L, Zhu H, Taylor FB Jr, 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(4): 1161-72.
25. Bach R, Rifkin DB. Expression of tissue factor procoagulant activity: regulation by cytosolic calcium. Proc Natl Acad Sci USA 1990; 87(18): 6995-9.
26. Carson SD, Nerry GA, Pirruccello SJ. Fibroblast tissue factor: Calcium and ionophore induce shape changes, release of membrane vesicles, and redistribution of tissue factor antigen in addition to increased procoagulant activity. Blood 1994; 84(2): 526-34.
27. Bach RR. Tissue factor encryption. Arterioscler Thromb Vasc Biol 2006; 26(3): 456-61.
28. Greeno EW, Bach RR, Moldow CF. Apoptosis is associated with increased cell surface tissue factor procoagulant activity. Lab Invest 1996; 75(2): 291-9.
29. Mandal SK, Pendurthi UR, Rao LV. Cellular localization and trafficking of tissue factor. Blood 2006; 107(12): 4746-53.
30. Pawlinski R, Mackman N. Tissue factor, coagulation proteases, and protease-activated receptors in endotaxemia and sepsis. Crit Care Med 2004; 32(5 Suppl): S293-7.
31. Pawlinski R, Pedersen B, Schabbauer G, Tencati M, Holscher T, Boisvert W, et al. Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia. Blood 2004; 103(4): 1342-7.
32. Welty-Wolf KE, Carraway MS, Ortel TL, Ghio AJ, Idell S, Egan J, et al. Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory and renal failure. Am J Physiol Lung Cell Mol Physiol 2006; 290(1): L21-31.
33. Carraway MS, Welty-Wolf KE, Miller DL, Ortel TL, Idell S, Ghio AJ, et al. Blockade of tissue factor: Treatment for organ injury in established sepsis. Am J Respir Crit Care Med 2003; 167(9): 1200-9.
34. Marsik C, Quehenberger P, Mackman N, Osterud B, Luther T, Jilma B. Validation of a novel tissue factor assay in experimental human endotaxemia. Thromb Res 2003; 111(4-5): 311-5.
35. Gando S, Nanzaki S, Morimoto Y, Kobayashi S, Kemmotsu O. Systemic activation of tissue-factor dependent coagulation pathway in evolving acute respiratory distress syndrome in patients with trauma and sepsis. J Trauma 1999; 47(4): 719-23.
36. Franco RF, de Jonge E, Dekkers PE, Timmerman JJ, Spek CA, van Deventer SJ, et al. The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: Relationship with activation of coagulation. Blood 2000; 96(2): 554-9.
37. Price GC, Thompson SA, Kam PC. Tissue factor and tissue factor pathway inhibitor. Anaesthesia 2004; 59(5):483-92.
38. 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 USA 1990; 87(22): 8869-73.
39. Osterud B, Bajaj MS, Bajaj SP. Sites of tissue factor pathway inhibitor (TFPI) and tissue factor expression under physiologic and pathologic conditions. On behalf of the Subcommittee on Tissue factor Pathway Inhibitor (TFPI) of the Scientific and Standardization Committee of the ISTH. Thromb Haemost 1995; 73(5): 873-5.
40. Ravindranath TM, Goto M, Iqbal O, Florian-Kujawski M, Hoppensteadt D, Hammadeh R, et al. Plasma thrombin activatable fibrinolysis inhibitor and tissue factor pathway inhibitor changes following sepsis. Clin Appl Thromb Hemost 2007; 13(4): 362-8.
41. Novotny WF, Palmier M, Wun TC, Broze GJ Jr, Miletich JP. Purification and properties of heparin-releasable lipoprotein-associated coagulation inhibitor. Blood 1991; 78(2): 394-400.
42. Asakura H, Ontachi Y, Mizutani T, Kato M, Saito M, Morishita E, et al. Elevated levels of free tissue factor pathway inhibitor antigen in cases of disseminated intravascular coagulation caused by various underlying diseases. Blood Coagul Fibrinolysis 2001; 12(1): 1-8.
43. Gando S, Nanzaki S, Morimoto D Y, Ishitani T, Kemmotsu O. Tissue factor pathway inhibitor response does not correlate with tissue factor-induced disseminated intravascular coagulation and multiple organ dysfunction syndrome in trauma patients. Crit Care Med 2001;29(2): 262-6.
44. Gando S, Kameue T, Morimoto Y, Matsuda N, Hayakawa M, Kemmotsu O. Tissue factor production not balanced by tissue factor pathway inhibitor in sepsis promotes poor prognosis. Crit Care Med 2002; 30(8): 1729-34.
45. Camerer E, Cornelissen I, Kataoka H, Duong DN, Zheng YW, Coughlin SR. Roles of protease-activated receptors in a mouse model of endotoxemia. Blood 2006; 107(10): 3912-21.
46. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000; 407(6801): 258-64.
47. Steinhoff M, Buddenkotte J, Shpacovitch V, Rattenholl A, Moormann C, Vergnolle N, et al. Proteinase-activated receptors: Transducers of proteinase-mediated signaling in inflammation and immune response. Endocr Rev 2005; 26(1): 1-43.
48. Cunningham MA, Romas P, Hutchinson P, Holdsworth SR, Tipping PG. Tissue factor and factor VIIa receptor/ligand interactions induce proinflammatory effects in macrophages. Blood 1999; 94(10): 3413-20
49. Awasthi V, Mandal SK, Papanna V, Rao LV, Pendurthi UR. Modulation of tissue factor-factor VIIa signaling by lipid rafts and caveolae. Arterioscler Thromb Vasc Biol 2007; 27(6): 1447-55.
50. van Hinsbergh VW, van den Berg EA, Fiers W, Dooijewaard G. Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells. Blood 1990; 75(10): 1991-8.
51. Yamamoto C, Kaji T, Furuya M, Sakamoto M, Kozuka H, Koizumi F. Basic fibroblast growth factor suppresses tissue plasminogen activator release from cultured human umbilical vein endothelial cells but enhances that from cultured human aortic endothelial cells. Thromb Res 1994; 73(3-4): 255-63.
52. Hou B, Eren M, Painter CA, Covington JW, Dixon JD, Schoenhard JA, et al. Tumor necrosis factor alpha activates the human plasminogen activator inhibitor-1 gene through a distal nuclear factor kappaB site. J Biol Chem 2004; 279(18): 18127-36.
53. Yamashita M, Yamashita M. Tumor necrosis factor alpha is involved in the induction of plasminogen activator inhibitor-1 by endotoxin. Thromb Res 1997; 87(2): 165-70.
54. Eitzman DT, McCoy RD, Zheng Y, Fay WP, Shen T, Ginsburg D, et al. Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene. Clin Invest 1996; 97(1): 232-7.
55. van Deventer SJ, Buller HR, ten Cate JW, Aarden LA, Hack CE, Stark A. Experimental endotoxemia in humans: Analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 1990; 76(12): 2520-6.
56. Pralong G, Calandra T, Glauser MP, Schellekens J, Verhoef J, Bachmann F, et al. Plasminogen activator inhibitor 1: A new prognostic marker in septic shock. Thromb Haemost 1989; 61(3): 459-62.
57. Brandtzaeg P, Joo GB, Brusletto B, Kierulf P. Plasminogen activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease. Thromb Res 1990; 57(2): 271-8.
58. Gando S, Nakanishi Y, Tedo I. Cytokines and plasminogen activator inhibitor-1 in posttrauma disseminated intravascular coagulation: relationship to multiple organ dysfunction syndrome. Crit Care Med 1995-123(11): 1835-42.
59. Mesters RM, Florke N, Ostermann H, Kienast J. Increase of plasminogen activator inhibitor levels predicts outcome of leukocytopenic patients with sepsis. Thromb Haemost 1996; 75(6): 902-7.
60. Raaphorst J, Johan Groeneveld AB, Bossink AW, Erik Hack C. Early inhibition of activated fibrinolysis predicts microbial infection, shock and mortality in febrile medical patients. Thromb Haemost 2001; 86(2): 543-9.
61. Hermans PW, Hibberd ML, Booy R, Daramola O, Hazelzet JA, de Groot R, et al. 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Meningococcal Research Group. Lancet 1999; 354(9178): 556-60.
62. Yende S, Angus DC, Ding J, Newman AB, Kellum JA, Li R, et al. 4G/ 5G plasminogen activator inhibitor-1 polymorphisms and haplotypes are associated with pneumonia. Am J Respir Crit Care Med 2007; 176(11): 1129-37.
63. Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor. J Biol Chem 1995; 270(24): 14477-84.
64. Bouma BN, Marx PF, Mosnier LO, Meijers JC. Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). Thromb Res 2001; 101(5): 329-54.
65. Sato T, Miwa T, Akatsu H, Matsukawa N, Obata K, Okada N, et al. Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not. J Immunol 2000; 165(2): 1053-8.
66. Kremer Hovinga JA, Franco RF, Zago MA, Ten Cate H, Westendorp RG, Reitsma PH. A functional single nucleotide polymorphism in the thrombin-activatable fibrinolysis inhibitor (TAFI) gene associates with outcome of meningococcal disease. J Thromb Haemost 2004; 2(1): 54-7.
67. Zeerleder S, Schroeder V, Hack CE, Kohler HP, Wuillemin WA. TAFI and PAI-1 levels in human sepsis. Thromb Res 2006; 118(2): 205-12.
68. Esmon CT. The protein C pathway. Chest 2003; 124(3 Suppl): 26S-32S.
69. Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT. The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci USA 1996; 93(19): 10212-6.
70. Esmon CT. Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflammation. Crit Care Med 2001; 29(7 Suppl): S48-51; discussion 51-2.
71. Shimizu S, Gabazza EC, Taguchi O, Yasui H, Taguchi Y, Hayashi T, et al. Activated protein C inhibits the expression of platelet-derived growth factor in the lung. Am J Respir Crit Care Med 2003; 167(10):1416-26.
72. Sakata Y, Loskutoff DJ, Gladson CL, Hekman CM, Griffin JH. Mechanism of protein C-dependent clot lysis: Role of plasminogen activator inhibitor. Blood 1996; 68(6): 1218-23.
73. Taylor FB Jr, Chang A, Esmon CT, D'Angelo A, Vigano-D'Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987; 79(3): 918-25.
74. Ganopolsky JG, Castellino FJ. A protein C deficiency exacerbates inflammatory and hypotensive responses in mice during polymicrobial sepsis in a cecal ligation and puncture model. Am J Pathol 2004; 165(4): 1433-46.
75. Shoff AF, Bernard GR, Dhainaut JF, Russell JR, Macias WL, Nelson DR, et al. Protein C concentrations in severe sepsis: An early directional change in plasma levels predicts outcome. Crit Care 2006; 10(3): R92.
76. Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR. Low levels of protein C are associated with poor outcome in severe sepsis. Chest 2001; 120(3): 915-22.
77. Liaw PC, Esmon CT, Kahnamoui K, Schmidt S, Kahnamoui S, Ferrell G, et al. Patients with severe sepsis vary markedly in their ability to generate activated protein C. Blood 2004; 104(13): 3958-64.
78. Faust SN, Levin M, Harrison OB, Goldin RD, Lockhart MS, Kondaveeti S, et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med 2001; 345(6): 408-16.
79. Wang L, Bastarache JA, Wickersham N, Fang X, Matthay MA, Ware LB. Novel role of the human alveolar epithelium in regulating intra-alveolar coagulation. Am J Respir Cell Mol Biol 2007; 36(4): 497-503.
80. Parrillo JE. Severe sepsis and therapy with activated protein C. N Engl J Med 2005; 353(13): 1398-400.
81. Levi M, Levy M, Williams MD, Douglas I, Artigas A, Antonelli M, et al. Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated). Am J Respir Crit Care Med 2007; 176(5): 483-90.
82. Bernard GR, Ely EW, Wright TJ, Fraiz J, Stasek JE Jr, Russell JA, et al. Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis. Crit Care Med 2001; 29(11): 2051-9.
83. Bernard GR, Margolis BD, Shanies HM, Ely EW, Wheeler AP, Levy H, et al. Extended evaluation of recombinant human activated protein C United States Trial (ENHANCE US): A single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest 2004; 125(6): 2206-16.
84. Nadel S, Goldstein B, Williams MD, Dalton H, Peters M, Macias WL, et al. Drotrecogin alfa (activated) in children with severe sepsis: A multicentre phase III randomised controlled trial. Lancet 2007; 369(9564): 836-43.
85. Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005; 353(13): 1332-41.
86. Angus DC, Laterre PF, Helterbrand J, Ely EW, Ball DE, Garg R, et al. The effect of drotrecogin alfa (activated) on long-term survival after severe sepsis. Crit Care Med 2004; 32(11): 2199-206.
87. Fowler RA, Hill-Popper M, Stasinos J, Petrou C, Sanders GD, Garber AM. Cost-effectiveness of recombinant human activated protein C and the influence of severity of illness in the treatment of patients with severe sepsis. J Crit Care 2003; 18(3): 181-91; discussion 191-4.
88. Angus DC, Linde-Zwirble WT, Clermont G, Ball DE, Basson BR, Ely EW, et al. Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis. Crit Care Med 2003; 31(1): 1-11.
89. Manns BJ, Lee H, Doig CJ, Johnson D, Donaldson C. An economic evaluation of activated protein C treatment for severe sepsis. N Engl J Med 2002; 347(13): 993-1000.
90. John J, Awab A, Norman D, Dernaika T, Kinasewitz GT. Activated protein C improves survival in severe sepsis patients with elevated troponin. Intensive Care Med 2007; 33(12): 2122-8.
91. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, et al. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: A randomized controlled trial. Jama 2001; 286(15): 1869-78.
92. Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, et al. Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: A randomized controlled trial. Jama 2003; 290(2): 238-47.
93. White B, Schmidt M, Murphy C, Livingstone W, O'Toole D, Lawler M, et al. Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line. Br J Haematol 2000; 110(1): 130-4.
94. Joyce DE, Gelbert L, Ciaccia A, DeHoff B, Grinnell BW. Gene expression profile of antithrombotic protein c defines new mechanisms modulating inflammation and apoptosis. J Biol Chem 2001; 276(14): 11199-203.
95. Bilbault P, Lavaux T, Launoy A, Gaub MP, Meyer N, Oudet P, et al. Influence of drotrecogin alpha (activated) infusion on the variation of Bax/Bcl-2 and Bax/Bcl-xl ratios in circulating mono-nuclear cells: A cohort study in septic shock patients. Crit Care Med 2007; 35(1): 69-75.
96. Mosnier LO, Zlokovic BV, Griffin JH. The cyloprotective protein C pathway. Blood 2007; 109(8): 3161-72.
97. Looney MR, Matthay MA. Bench-to-bedside review: The role of activated protein C in maintaining endothelial tight junction function and its relationship to organ injury. Crit Care 2006; 10(6): 239.
98. Taylor FB Jr, Stearns-Kurosawa DJ, Kurosawa S, Ferrell G, Chang AC, Laszik Z, et al. The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. Blood 2000; 95(5): 1680-6.
99. Nick JA, Coldren CD, Geraci MW, Poch KR, Fouty BW, O'Brien J, et al. Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis. Blood 2004; 104(13): 3878-85.
100. Kerschen EJ, Fernandez JA, Cooley BC, Yang XV, Sood R, Mosnier LO, et al. Endotoxemia and sepsis mortality reduction by nonanticoagulant activated protein C. J Exp Med 2007; 204(10): 2439-48.
101. Jilma B, Marsik C, Mayr F, Graninger MT, Taylor FB Jr, Ribel MC, et al. Pharmacodynamics of active site-inhibited factor VIIa in ondotoxin-induced coagulation in humans. Clin Pharmacol Ther 2002; 72(4): 403-10.
102. Camerota AJ, Creasey AA, Patla V, Larkin VA, Fink MT. Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis. J Infect Dis 1998; 177(3): 668-76.
103. Creasey AA, Chang AC, Feigen L, Wun TC, Taylor FB Jr, Hinshaw LB. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 1993; 91(6): 2850-60.
104. Enkhbaatar P, Okajima K, Murakami K, Uchiba M, Okabe H, Okabe Y, 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(5): 1752-9
105. Abraham E, Reinhart K, Svoboda P, Seibert A, Olthoff D, Dal Nogare A, 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): 2081-9.
106. Esmon CT, Owen WG. The discovery of thrombomodulin. J Thromb Haemost 2004; 2(2): 209-13.
107. Van de Wouwer M, Collen D, Conway EM. Thrombomodulinprotein C-EPCR system: Integrated to regulate coagulation and inflammation. Arterioscler Thromb Vasc Biol 2004; 24(8): 1374-83.
108. Dhainaut JF, Yan SB, Cariou A, Mira JP. Soluble thrombomodulin, plasma-derived unactivated protein C, and recombinant human activated protein C in sepsis. Crit Care Med 2002; 30(5 Suppl): S318-24.
109. Saito H, Maruyama I, Shimazaki S, Yamamoto Y, Aikawa N, Ohno R, et al. Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: Results of a phase III, randomized, double-blind clinical trial. J Thromb Haemost 2007; 5(1): 31-41.
110. Opal SM, Kessler CK Roemisch J, Knaub S. Antithrombin, heparin, and heparan sulfate, Crit Care Med 2002; 30(5 Suppl): S325-31.
111. Niessen RW, Lamping RJ, Jansen PM, Prins MH, Peters M, Taylor FB Jr, et al. Antithrombin acts as a negative acute phase protein as established with studies on HepG2 cells and in baboons. Thromb Haemost 1997; 78(3): 1088-92.
112. Minnema MC, Chang AC, Jansen PM, Lubbers YT, Pratt BM, Whittaker BG, el al. Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli. Blood 2000; 95(4):1117- 23.
113. Dickniete G. Antithrombin III in animal models of sepsis and organ failure. Semin Thromb Hemost 1998; 24(1): 61-9.
114. Cornet AD, Smit EG, Beishuizen A, Groeneveld AB. The role of heparin and allied compounds in the treatment of sepsis. Thromb Haemost 2007; 98(3): 579-86.
115. Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R, et al. Heparin and low-molecular-weight heparin: Mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 2001; 119(Suppl 1): 64S-94S.
116. Day JR, Landis RC, Taylor KM. Heparin is much more than just an anticoagulant. J Cardiothorac Vasc Anesth 2004; 18(1): 93-100.
117. Ahmed T, Gonzalez BJ, Danta I. Prevention of exercise-induced bronchoconstriction by inhaled low-molecular-weight beparin. Am J Respir Crit Care Med 1999; 160(2): 576-81.
118. Pechlaner C, Buratti T, Biedermann H, Joannidis M, Wiedermann CJ. Thrombolytic therapy in adult meningococcal purpura fulminans with acute renal failure and severe perfusion deficits to the extremities. Wien Klin Wochenschr 1999; 11l(16): 650-4.
119. Aiuto LT, Barone SR, Cohen PS, Boxer RA. Recombinant tissue plasminogen activator restores perfusion in meningococcal purpura fulminans. Crit Care Med 1997; 25(6): 1079-82.
120. Hardaway RK, Harke H, Tyroch AH, Williams CH, Vazquez Y, Krause GF. Treatment of severe acute respiratory distress syndrome: A final report on a phase I study. Am Surg 2001; 67(4): 377- 82.
121. Gils A, Declerck PJ. The structural basis for the pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors. Thromb Haemost 2004; 91(3): 425-37.
122. Munoz MC, Montes R, Hermida, J, Orbe J, Paramo JA, Rocha E. Effect of the administration of recombinant hirudin and/or tissueplasminogen activator (t-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits. Br J Haematol 1999; 105(1): 117-21.
123. Vasquez Y, Williams CH, Hardaway RM. Effect of urokinase on disseminated intravascular coagulation. J Appl, Physiol 1999; 85(4): 1421-8.
124. Durukan A, Strbian D, Tatlisumak T. Rodent models of ischemic stroke: A useful tool for stroke drug development. Curr Pharm Des 2008; 14(4): 359-70.
125. Prezelj A, Anderluh PS, Peternel L, Urleb U. Recent advances in serine protease inhibitors as anticoagulant agents. Curr Pharm Des 2007; 13(3): 287-312.
126. Vanhoorelbeke K, Ulrichts H, Van de Walle G, Foritayne, A, Deckinyn H. Inhibition of platelet glycoprotein lb and its antithrombotic potential. Curr Pharm Des 2007; 13(26): 2684-97.