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Coagulation in sepsis

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Abstract

Coagulation abnormalities, ranging from a simple fall in platelet count to full-blown disseminated intravascular coagulation, are a common occurrence in critically ill patients and have been associated with increased mortality. In sepsis, activation of the extrinsic coagulation pathway by tissue factor induces increased coagulation, and simultaneous depression of the inhibitory mechanisms of coagulation, and suppression of the fibrinolytic system results in a procoagulant state that may lead to the formation of microvascular thrombi disturbing organ microcirculation and promoting the development of organ dysfunction. Many inflammatory mediators are involved in the activation of coagulation, but many coagulation proteins are themselves actively involved in the inflammatory process. In this article, we explore the complex relationship between inflammation and coagulation and how improved understanding of this interaction has led to the development of new therapeutic agents for patients with severe sepsis.

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References

  1. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709

    CAS  PubMed  Google Scholar 

  2. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Penzes I, Kubler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM (2001) Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA 286:1869–1878

    CAS  PubMed  Google Scholar 

  3. Abraham E, Reinhart K, Opal S, Demeyer I, Doig C, Rodriguez AL, Beale R, Swoboda P, Laterre PF, Simon S, Light B, Spapen H, Stone J, Seibert A, Pekelseln C, De Deyner C, Postier R, Pettila V, Artigas A, Percell SR, Shu V, Zwingelstein C, Tobis J, Poole L, Stolzenbach JC, Creasy AA, OPTIMIST Trial Study Group (2003) Efficacy and safety of tifacogin (recombinant tissue factor pathway inhibitor) in severe sepsis: a randomized controlled trial. JAMA 290:238–247

    Article  CAS  PubMed  Google Scholar 

  4. Davie EW, Ratnoff OD (1964) Waterfall sequence for intrinsic blood clotting. Science 145:1310–1312

    CAS  Google Scholar 

  5. MacFarlane RG (1964) An enzyme cascade in the blood clotting mechanism, and its function as a biological amplifier. Nature 202:498–499

    CAS  Google Scholar 

  6. Hoffman M, Monroe DM III (2001) A cell-based model of hemostasis. Thromb Haemost 85:958–965

    CAS  PubMed  Google Scholar 

  7. van’t Veer C, Mann KG (1997) Regulation of tissue factor initiated thrombin generation by the stoichiometric inhibitors tissue factor pathway inhibitor, antithrombin- III, and heparin cofactor-II. J Biol Chem 272:4367–4377

    Article  PubMed  Google Scholar 

  8. Osterud B (1998) Tissue factor expression by monocytes: regulation and pathophysiological roles. Blood Coagul Fibrinolysis 9[Suppl 1]:S9–14

    Google Scholar 

  9. Osterud B, Rapaport SI (1977) Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation. Proc Natl Acad Sci USA 74:5260–5264

    CAS  PubMed  Google Scholar 

  10. Morrissey JH, Macik BG, Neuenschwander PF, Comp PC (1993) Quantitation of activated factor VII levels in plasma using a tissue factor mutant selectively deficient in promoting factor VII activation. Blood 81:734–744

    CAS  PubMed  Google Scholar 

  11. Nemerson Y, Repke D (1985) Tissue factor accelerates the activation of coagulation factor VII: the role of a bifunctional coagulation cofactor. Thromb Res 40:351–358

    Article  CAS  PubMed  Google Scholar 

  12. Morrissey JH (2001) Tissue factor: an enzyme cofactor and a true receptor. Thromb Haemost 86:66–74

    CAS  PubMed  Google Scholar 

  13. Nakagaki T, Foster DC, Berkner KL, Kisiel W (1991) Initiation of the extrinsic pathway of blood coagulation: evidence for the tissue factor dependent autoactivation of human coagulation factor VII. Biochemistry 30:10819–10824

    CAS  PubMed  Google Scholar 

  14. Neuenschwander PF, Fiore MM, Morrissey JH (1993) Factor VII autoactivation proceeds via interaction of distinct protease- cofactor and zymogen-cofactor complexes. Implications of a two- dimensional enzyme kinetic mechanism. J Biol Chem 268:21489–21492

    CAS  PubMed  Google Scholar 

  15. Diaz-Ricart M, Estebanell E, Lozano M, Aznar-Salatti J, White JG, Ordinas A, Escolar G (2000) Thrombin facilitates primary platelet adhesion onto vascular surfaces in the absence of plasma adhesive proteins: studies under flow conditions. Haematologica 85:280–288

    CAS  PubMed  Google Scholar 

  16. Sambrano GR, Weiss EJ, Zheng YW, Huang W, Coughlin SR (2001) Role of thrombin signalling in platelets in haemostasis and thrombosis. Nature 413:74–78

    Article  CAS  PubMed  Google Scholar 

  17. Monroe DM, Hoffman M, Roberts HR (1996) Transmission of a procoagulant signal from tissue factor-bearing cell to platelets. Blood Coagul Fibrinolysis 7:459–464

    CAS  PubMed  Google Scholar 

  18. Romp KG, Monroe DM, Hoffman M (1993) Platelets contain releasable coagulation factor IX antigen. Blood Coagul Fibrinolysis 4:905–910

    CAS  PubMed  Google Scholar 

  19. Mosesson MW (1992) The roles of fibrinogen and fibrin in hemostasis and thrombosis. Semin Hematol 29:177–188

    CAS  PubMed  Google Scholar 

  20. Schwartz ML, Pizzo SV, Hill RL, McKee PA (1971) The subunit structures of human plasma and platelet factor XIII (fibrin- stabilizing factor). J Biol Chem 246:5851–5854

    CAS  PubMed  Google Scholar 

  21. Redlitz A, Tan AK, Eaton DL, Plow EF (1995) Plasma carboxypeptidases as regulators of the plasminogen system. J Clin Invest 96:2534–2538

    CAS  PubMed  Google Scholar 

  22. Pizzo SV, Schwartz ML, Hill RL, McKee PA (1973) The effect of plasmin on the subunit structure of human fibrin. J Biol Chem 248:4574–4583

    CAS  PubMed  Google Scholar 

  23. Weitz JI, Stewart RJ, Fredenburgh JC (1999) Mechanism of action of plasminogen activators. Thromb Haemost 82:974–982

    CAS  PubMed  Google Scholar 

  24. Idell S (2002) Endothelium and disordered fibrin turnover in the injured lung: newly recognized pathways. Crit Care Med 30:S274–S280

    Article  CAS  PubMed  Google Scholar 

  25. Broze GJ Jr (1992) Why do hemophiliacs bleed? Hosp Pract (Off Ed) 27:71–82,85

    Google Scholar 

  26. Sanders NL, Bajaj SP, Zivelin A, Rapaport SI (1985) Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component. Blood 66:204–212

    CAS  PubMed  Google Scholar 

  27. Blajchman MA, Austin RC, Fernandez-Rachubinski F, Sheffield WP (1992) Molecular basis of inherited human antithrombin deficiency. Blood 80:2159–2171

    CAS  PubMed  Google Scholar 

  28. Marciniak E (1973) Factor-Xa inactivation by antithrombin. 3. Evidence for biological stabilization of factor Xa by factor V-phospholipid complex. Br J Haematol 24:391–400

    CAS  PubMed  Google Scholar 

  29. Esmon CT (1989) The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 264:4743–4746

    CAS  PubMed  Google Scholar 

  30. Kisiel W (1979) Human plasma protein C: isolation, characterization, and mechanism of activation by alpha-thrombin. J Clin Invest 64:761–769

    CAS  PubMed  Google Scholar 

  31. Stearns-Kurosawa DJ, Kurosawa S, Mollica JS, Ferrell GL, Esmon CT (1996) The endothelial cell protein C receptor augments protein C activation by the thrombin-thrombomodulin complex. Proc Natl Acad Sci U S A 93:10212–10216

    Article  CAS  PubMed  Google Scholar 

  32. Sakata Y, Loskutoff DJ, Gladson CL, Hekman CM, Griffin JH (1986) Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor. Blood 68:1218–1223

    CAS  PubMed  Google Scholar 

  33. Esmon CT (2000) Introduction: are natural anticoagulants candidates for modulating the inflammatory response to endotoxin? Blood 95:1113–1116

    CAS  PubMed  Google Scholar 

  34. Esmon CT (2001) Role of coagulation inhibitors in inflammation. Thromb Haemost 86:51–56

    CAS  PubMed  Google Scholar 

  35. Schaub RG, Simmons CA, Koets MH, Romano PJ, Stewart GJ (1984) Early events in the formation of a venous thrombus following local trauma and stasis. Lab Invest 51:218–224

    CAS  PubMed  Google Scholar 

  36. Yang J, Furie BC, Furie B (1999) The biology of P-selectin glycoprotein ligand-1: its role as a selectin counterreceptor in leukocyte-endothelial and leukocyte-platelet interaction. Thromb Haemost 81:1–7

    Google Scholar 

  37. Coughlan AF, Hau H, Dunlop LC, Berndt MC, Hancock WW (1994) P-selectin and platelet-activating factor mediate initial endotoxin- induced neutropenia. J Exp Med 179:329–334

    CAS  PubMed  Google Scholar 

  38. Lim YC, Snapp K, Kansas GS, Camphausen R, Ding H, Luscinskas FW (1998) Important contributions of P-selectin glycoprotein ligand-1-mediated secondary capture to human monocyte adhesion to P-selectin, E-selectin, and TNF-alpha-activated endothelium under flow in vitro. J Immunol 161:2501–2508

    CAS  PubMed  Google Scholar 

  39. Ramasamy S, Lipke DW, McClain CJ, Hennig B (1995) Tumor necrosis factor reduces proteoglycan synthesis in cultured endothelial cells. J Cell Physiol 162:119–126

    CAS  PubMed  Google Scholar 

  40. Klein NJ, Shennan GI, Heyderman RS, Levin M (1992) Alteration in glycosaminoglycan metabolism and surface charge on human umbilical vein endothelial cells induced by cytokines, endotoxin and neutrophils. J Cell Sci 102[Pt 4]:821–832

  41. Conway EM, Rosenberg RD (1988) Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Mol Cell Biol 8:5588–5592

    CAS  PubMed  Google Scholar 

  42. Murugesan G, Rani MR, Ransohoff RM, Marchant RE, Kottke-Marchant K (2000) Endothelial cell expression of monocyte chemotactic protein-1, tissue factor, and thrombomodulin on hydrophilic plasma polymers. J Biomed Mater Res 49:396–408

    Article  CAS  PubMed  Google Scholar 

  43. Moore KL, Andreoli SP, Esmon NL, Esmon CT, Bang NU (1987) Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. J Clin Invest 79:124–130

    CAS  PubMed  Google Scholar 

  44. Creasey AA, Chang AC, Feigen L, Wun TC, Taylor FBJ, Hinshaw LB (1993) Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 91:2850–2856

    CAS  PubMed  Google Scholar 

  45. de Jonge E, Dekkers PE, Creasey AA, Hack CE, Paulson SK, Karim A, Kesecioglu J, Levi M, Van Deventer SJ, van der PT (2000) Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood 95:1124–1129

    PubMed  Google Scholar 

  46. de Jonge E, Dekkers PE, Creasey AA, Hack CE, Paulson SK, Karim A, Kesecioglu J, Levi M, Van Deventer SJ, van der PT (2001) Tissue factor pathway inhibitor does not influence inflammatory pathways during human endotoxemia. J Infect Dis 183:1815–1818

    Article  PubMed  Google Scholar 

  47. Opal SM, Palardy JE, Parejo NA, Creasey AA (2001) The activity of tissue factor pathway inhibitor in experimental models of superantigen-induced shock and polymicrobial intra-abdominal sepsis. Crit Care Med 29:13–17

    Google Scholar 

  48. Yamauchi T, Umeda F, Inoguchi T, Nawata H (1989) Antithrombin III stimulates prostacyclin production by cultured aortic endothelial cells. Biochem Biophys Res Commun 163:1404–1411

    CAS  PubMed  Google Scholar 

  49. Harada N, Okajima K, Kushimoto S, Isobe H, Tanaka K (1999) Antithrombin reduces ischemia/reperfusion injury of rat liver by increasing the hepatic level of prostacyclin. Blood 93:157–164

    CAS  PubMed  Google Scholar 

  50. Ostrovsky L, Woodman RC, Payne D, Teoh D, Kubes P (1997) Antithrombin III prevents and rapidly reverses leukocyte recruitment in ischemia/reperfusion. Circulation 96:2302–2310

    CAS  PubMed  Google Scholar 

  51. Uchiba M, Okajima K (1997) Antithrombin III (AT III) prevents LPS-induced pulmonary vascular injury: novel biological activity of AT III. Semin Thromb Hemost 23:583–590

    CAS  PubMed  Google Scholar 

  52. Totzke G, Schobersberger W, Schloesser M, Czechowski M, Hoffmann G (2001) Effects of antithrombin III on tumor necrosis factor-alpha and interleukin-1beta synthesis in vascular smooth muscle cells. J Interferon Cytokine Res 21:1063–1069

    Article  CAS  PubMed  Google Scholar 

  53. Grey ST, Tsuchida A, Hau H, Orthner CL, Salem HH, Hancock WW (1994) Selective inhibitory effects of the anticoagulant activated protein C on the responses of human mononuclear phagocytes to LPS, IFN-gamma, or phorbol ester. J Immunol 153:3664–3672

    CAS  PubMed  Google Scholar 

  54. Hirose K, Okajima K, Taoka Y, Uchiba M, Tagami H, Nakano K, Utoh J, Okabe H, Kitamura N (2000) Activated protein C reduces the ischemia/reperfusion-induced spinal cord injury in rats by inhibiting neutrophil activation. Ann Surg 232:272–280

    Article  CAS  PubMed  Google Scholar 

  55. Murakami K, Okajima K, Uchiba M, Johno M, Nakagaki T, Okabe H, Takatsuki K (1997) Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production. Am J Physiol 272:L197–L202

    CAS  PubMed  Google Scholar 

  56. Taylor F, Chang A, Ferrell G, Mather T, Catlett R, Blick K, Esmon CT (1991) C4b-binding protein exacerbates the host response to Escherichia coli. Blood 78:357–363

    CAS  PubMed  Google Scholar 

  57. Taylor FB, Jr., Stearns-Kurosawa DJ, Kurosawa S, Ferrell G, Chang AC, Laszik Z, Kosanke S, Peer G, Esmon CT (2000) The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. Blood 95:1680–1686

    CAS  PubMed  Google Scholar 

  58. White B, Schmidt M, Murphy C, Livingstone W, O’Toole D, Lawler M, O’Neill L, Kelleher D, Schwarz HP, Smith OP (2000) 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 110:130–134

    Article  CAS  PubMed  Google Scholar 

  59. Joyce DE, Gelbert L, Ciaccia A, DeHoff B, Grinnell BW (2001) Gene expression profile of antithrombotic protein c defines new mechanisms modulating inflammation and apoptosis. J Biol Chem 276:11199–11203

    Article  CAS  PubMed  Google Scholar 

  60. Esmon CT (2001) Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflammation. Crit Care Med 29:S48–S51

    Google Scholar 

  61. Rocha E, Paramo JA, Montes R, Panizo C (1998) Acute generalized, widespread bleeding. Diagnosis and management. Haematologica 83:1024–1037

    CAS  PubMed  Google Scholar 

  62. Gando S, Nanzaki S, Sasaki S, Aoi K, Kemmotsu O (1998) Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock. Crit Care Med 26:2005–2009

    Google Scholar 

  63. Hesselvik FJ, Blomback M, Brodin B, Maller R (1989) Coagulation, fibrinolysis and kallikrein systems in sepsis: relation to outcome. Crit Care Med 17:724–733

    CAS  PubMed  Google Scholar 

  64. McGee MP, Foster S, Wang X (1994) 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 179:1847–1854

    CAS  PubMed  Google Scholar 

  65. Rana SV, Reimers HJ, Pathikonda MS, Bajaj SP (1988) Expression of tissue factor and factor VIIa/tissue factor inhibitor activity in endotoxin or phorbol ester stimulated U937 monocyte-like cells. Blood 71:259–262

    CAS  PubMed  Google Scholar 

  66. Mesters RM, Mannucci PM, Coppola R, Keller T, Ostermann H, Kienast J (1996) Factor VIIa and antithrombin III activity during severe sepsis and septic shock in neutropenic patients. Blood 88:881–886

    CAS  PubMed  Google Scholar 

  67. Hesselvik JF, Malm J, Dahlback B, Blomback M (1991) Protein C, protein S and C4b-binding protein in severe infection and septic shock. Thromb Haemost 65:126–129

    PubMed  Google Scholar 

  68. Leithauser B, Matthias FR, Nicolai U, Voss R (1996) Hemostatic abnormalities and the severity of illness in patients at the onset of clinically defined sepsis. Possible indication of the degree of endothelial cell activation? Intensive Care Med 22:631–636

    CAS  PubMed  Google Scholar 

  69. Philippe J, Offner F, Declerck PJ, Leroux-Roels G, Vogelaers D, Baele G, Collen D (1991) Fibrinolysis and coagulation in patients with infectious disease and sepsis. Thromb Haemost 65:291–295

    PubMed  Google Scholar 

  70. Martinez MA, Pena JM, Fernandez A, Jimenez M, Juarez S, Madero R, Vazquez JJ (1999) Time course and prognostic significance of hemostatic changes in sepsis: relation to tumor necrosis factor-alpha. Crit Care Med 27:1303–1308

    CAS  PubMed  Google Scholar 

  71. Mavrommatis AC, Theodoridis T, Economou M, Kotanidou A, El Ali M, Christopoulou-Kokkinou V, Zakynthinos SG (2001) Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med 27:1853–1859

    Article  CAS  PubMed  Google Scholar 

  72. Opal SM (2000) Therapeutic rationale for antithrombin III in sepsis. Crit Care Med 28:S34–S37

    Article  CAS  PubMed  Google Scholar 

  73. Fijnvandraat K, Derkx B, Peters M, Bijlmer R, Sturk A, Prins MH, Van Deventer SJ, ten Cate JW (1995) Coagulation activation and tissue necrosis in meningococcal septic shock: severely reduced protein C levels predict a high mortality. Thromb Haemost 73:15–20

    CAS  PubMed  Google Scholar 

  74. Leclerc F, Hazelzet J, Jude B, Hofhuis W, Hue V, Martinot A, Van der Voort E (1992) Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Intensive Care Med 18:202–205

    CAS  PubMed  Google Scholar 

  75. Lorente JA, Garcia-Frade LJ, Landin L, De Pablo R, Torrado C, Renes E, Garcia-Avello A (1993) Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest 103:1536–1542

    CAS  PubMed  Google Scholar 

  76. Gando S, Kameue T, Nanzaki S, Nakanishi Y (1995) Cytokines, soluble thrombomodulin and disseminated intravascular coagulation in patients with systemic inflammatory response syndrome. Thromb Res 80:519–526

    Article  CAS  PubMed  Google Scholar 

  77. Ishii H, Uchiyama H, Kazama M (1991) Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells. Thromb Haemost 65:618–623

    CAS  PubMed  Google Scholar 

  78. Bajzar L, Nesheim ME, Tracy PB (1996) The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent. Blood 88:2093–2100

    CAS  PubMed  Google Scholar 

  79. Mosnier LO, Meijers JC, Bouma BN (2001) Regulation of fibrinolysis in plasma by TAFI and protein C is dependent on the concentration of thrombomodulin. Thromb Haemost 85:5–11

    CAS  PubMed  Google Scholar 

  80. Gando S, Nanzaki S, Sasaki S, Aoi K, Kemmotsu O (1998) Activation of the extrinsic coagulation pathway in patients with severe sepsis and septic shock. Crit Care Med 26:2005–2009

    Google Scholar 

  81. Mavromatis BH, Kessler CM (2001) D-dimer testing: the role of the clinical laboratory in the diagnosis of pulmonary embolism. J Clin Pathol 54:664–668

    CAS  PubMed  Google Scholar 

  82. Dofferhoff AS, Bom VJ, de Vries Hospers HG, van Ingen J, v.d.Meer J, Hazenberg BP, Mulder PO, Weits J (1992) Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acute-phase proteins during the treatment of severe sepsis in humans. Crit Care Med 20:185–192

    CAS  PubMed  Google Scholar 

  83. Watanabe R, Wada H, Watanabe Y, Sakakura M, Nakasaki T, Mori Y, Nishikawa M, Gabazza EC, Nobori T, Shiku H (2001) Activity and antigen levels of thrombin-activatable fibrinolysis inhibitor in plasma of patients with disseminated intravascular coagulation. Thromb Res 104:1–6

    Article  CAS  PubMed  Google Scholar 

  84. Amitrano L, Guardascione MA, Brancaccio V, Balzano A (2002) Coagulation disorders in liver disease. Semin Liver Dis 22:83–96

    Article  CAS  PubMed  Google Scholar 

  85. ten Cate H, Schoenmakers SH, Franco R, Timmerman JJ, Groot AP, Spek CA, Reitsma PH (2001) Microvascular coagulopathy and disseminated intravascular coagulation. Crit Care Med 29:S95–S97

    Article  PubMed  Google Scholar 

  86. van ‘t Veer C, Golden NJ, Kalafatis M, Mann KG (1997) Inhibitory mechanism of the protein C pathway on tissue factor-induced thrombin generation. Synergistic effect in combination with tissue factor pathway inhibitor. J Biol Chem 272:7983–7994

    Article  PubMed  Google Scholar 

  87. DePalo V, Kessler C, Opal SM (2001) Success or failure in phase III sepsis trials: comparisons between the Drotrecogin alfa (activated) and antithrombin III clinical trials. Adv Sepsis 1:114–124

    CAS  Google Scholar 

  88. Kessler CM, Tang Z, Jacobs HM, Szymanski LM (1997) The suprapharmacologic dosing of antithrombin concentrate for Staphylococcus aureus-induced disseminated intravascular coagulation in guinea pigs: substantial reduction in mortality and morbidity. Blood 89:4393–4401

    CAS  PubMed  Google Scholar 

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Correspondence to Jean-Louis Vincent.

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Competing interests: Dr SM Opal and Dr JL Vincent have been consultants for, and have received honorariums from, Aventis (antithrombin), Eli Lilly [drotrecogin alfa (activated)], and Chiron (tissue factor pathway inhibitor). Dr JL Vincent was the Principal Investigator of the European arm of the PROWESS study and principal investigator of the ENHANCE study (Eli Lilly) and an investigator for the TFPI study (Chiron). Dr Opal was the principal investigator for the Kybersept trial (Aventis), and was one of the North American investigators in the TFPI trial

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Amaral, A., Opal, S.M. & Vincent, JL. Coagulation in sepsis. Intensive Care Med 30, 1032–1040 (2004). https://doi.org/10.1007/s00134-004-2291-8

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