Skip to main content
SpringerLink
Log in
Book cover

Yearbook of Intensive Care and Emergency Medicine 2001 pp 113–122Cite as

Natural Anticoagulants in Disseminated Intravascular Coagulation and Sepsis

  • Conference paper

  • 209 Accesses

Part of the book series: Yearbook of Intensive Care and Emergency Medicine 2001 ((YEARBOOK,volume 2001))

Abstract

Disseminated intravascular coagulation (DIG) is a common feature of a wide variety of clinical conditions including septicemia, trauma, cancer, obstetrical complications, and some intoxications. Massive activation of the coagulation system may result in generation and deposition of fibrin, leading to microvascular thrombi and contributing to the development of multi-organ failure (MOF). As a consequence of consumption of platelets and coagulation factors, DIC may lead also to an increased risk of bleeding. Recent evidence suggests that the activation of coagulation during DIC may also elicit a pro-inflammatory response. In patients with sepsis, the severity of DIC has been shown to correlate with poor outcome [1]. The cornerstone for the treatment of DIC is optimal management of the underlying disease. Traditionally, replacement therapy with platelets and plasma is given to reduce the risk of bleeding, whereas heparin is administered to inhibit the activation of coagulation. However, these treatments are not based on firm evidence [2]. In this chapter, we will discuss the role of natural anticoagulant systems in the pathogenesis of DIC, and the potential of anticoagulant proteins as treatment modalities in patients with sepsis and DIC.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Fourrier F, Chopin C, Goudemand J, et al (1992) Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest 101:816–823

    Article  PubMed  CAS  Google Scholar 

  2. de Jonge E, Levi M, Stoutenbeek CP, van, Deventer S J (1998) Current drug treatment strategies for disseminated intravascular coagulation. Drugs 55:767–777

    Article  PubMed  Google Scholar 

  3. Levi M, ten Cate H (1999) Disseminated intravascular coagulation. N Engl J Med 341:586–592

    Article  PubMed  CAS  Google Scholar 

  4. Moldow CF, Bach RR, Staskus K, Rick PD (1993) Induction of endothehal tissue factor by endotoxin and its precursors. Thromb Haemost 70:702–706

    PubMed  CAS  Google Scholar 

  5. Rivers RP, Hathaway WE, Weston WL (1975) The endotoxin-induced coagulant activity of human monocytes. Br J Haematol 30:311–316

    Article  PubMed  CAS  Google Scholar 

  6. Francis JL, Biggerstaff J, Amirkhosravi A (1998) Hemostasis and malignancy. Semin Thromb Hemost 24:93–109

    Article  PubMed  CAS  Google Scholar 

  7. Lawson CA, Yan SD, Yan SF, et al (1997) Monocytes and tissue factor promote thrombosis in a murine model of oxygen deprivation. J Clin Invest 99:1729–1738

    Article  PubMed  CAS  Google Scholar 

  8. Levi M, ten Cate H, Bauer KA, et al (1994) Inhibition of endotoxin-induced activation of coagulation and fibrinolysis by pentoxifylline or by a monoclonal anti-tissue factor antibody in chimpanzees. J Clin Invest 93:114–120

    Article  PubMed  CAS  Google Scholar 

  9. Nuijens JH, Huijbregts CC, Eerenberg-Belmer AJ, et al (1988) Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(-)-inhibitor complexes in sepsis. Blood 72:1841–1848

    PubMed  CAS  Google Scholar 

  10. Taylor FBJ, Chang A, Ruf W, et al (1991) Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 33:127–134

    PubMed  Google Scholar 

  11. Taylor FB, Chang AC, Peer G, Li A, Ezban M, Hedner U (1998) 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 coh. Blood 91:1609–1615

    PubMed  CAS  Google Scholar 

  12. 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

    Article  PubMed  CAS  Google Scholar 

  13. Taylor FB (1999) Baboon model of E. coli sepsis: role of phospholipid microparticles in DIC. Sepsis 3:125–134

    Article  Google Scholar 

  14. Mann LTJ, Jensenius JC, Simonsen M, Abildgaard U (1969) Antithrombin 3. Protection against death after injection of thromboplastin. Science 166:517–518

    Article  PubMed  CAS  Google Scholar 

  15. Opal SM, Thijs LG (1999) New potential therapeutic modalities: Antithrombin III. Sepsis 3: 153–159

    Article  Google Scholar 

  16. Eisele B, Lamy M, Thijs LG, et al (1998) Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med 24:663–672

    CAS  Google Scholar 

  17. Levi M, de Jonge E, van der Poll T, ten Cate H (1999) Disseminated intravascular coagulation. Thromb Haemost 82:695–705

    PubMed  CAS  Google Scholar 

  18. Dickneite G (1998) Antithrombin III in animal models of sepsis and organ failure. Semin Thromb Hemost 24:61–69

    Article  PubMed  CAS  Google Scholar 

  19. Ilias W, List W, Decruyenaere J, et al (2000) Antithrombin III in patients with severe sepsis: a pharmacokinetic study. Intensive Care Med 26:704–715

    Article  PubMed  CAS  Google Scholar 

  20. Riess H (2000) Antithrombin in severe sepsis — “new” indication of an “old” drug?. Intensive Care Med 26:657–659

    Article  PubMed  CAS  Google Scholar 

  21. Dreyfus M, Magny JF, Bridey F, et al (1991) Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med 325:1565–1568

    Article  PubMed  CAS  Google Scholar 

  22. Esmon CT (1999) New potential therapeutic modalities: aPC. Sepsis 3:161–171

    Article  Google Scholar 

  23. Takahashi Y, Hosaka Y, Imada K, et al (1997) Human urinary soluble thrombomodulin (MR-33) improves disseminated intravascular coagulation without affecting bleeding time in rats: comparison with low molecular weight heparin. Thromb Haemost 77:789–795

    PubMed  CAS  Google Scholar 

  24. Uchiba M, Okajima K, Murakami K, Johno M, Okabe H, Takatsuki K (1997) Effect of human urinary thrombomodulin on endotoxin-induced intravascular coagulation and pulmonary vascular injury in rats. Am J Hematol 54:118–123

    Article  PubMed  CAS  Google Scholar 

  25. Mohri M, Gonda Y, Oka M, et al (1997) The antithrombotic effects of recombinant human soluble thrombomodulin (rhsTM) on tissue factor-induced disseminated intravascular coagulation in crab-eating monkeys (Macaca fascicularis). Blood Goagul Fibrinolysis 8:274–283

    Article  CAS  Google Scholar 

  26. Uchiba M, Okajima K, Murakami K, et al (1997) rhs-TM prevents ET-induced increase in pulmonary vascular permeability through protein C activation. Am J Physiol 273: L889–L894

    PubMed  CAS  Google Scholar 

  27. Maruyama I (1999) Recombinant thrombomodulin and activated protein C in the treatment of disseminated intravascular coagulation. Thromb Haemost 82:718–721

    PubMed  CAS  Google Scholar 

  28. Taylor FBJ, Ghang A, Esmon CT, D’Angelo A, Vigano-D’Angelo S, Blick KE (1987) Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 79:918–925

    Article  PubMed  CAS  Google Scholar 

  29. Taylor FBJ, Stearns-Kurosawa DJ, Kurosawa S, et al (2000) The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. Blood 95:1680–1686

    PubMed  CAS  Google Scholar 

  30. Ettingshausen CE, Veldmann A, Beeg T, Schneider W, Jager G, Kreuz W (1999) Replacement therapy with protein C concentrate in infants and adolescents with meningococcal sepsis and purpura fulminans. Semin Thromb Hemost 25:537–541

    Article  PubMed  CAS  Google Scholar 

  31. Bernard GR, Hartman DL, Helterbrand JD, Fisher CJ (1998) Recombinant human activated protein C (rhAPC) produces a trend toward impropvement in morbidity and 28 day survival in patients with severe sepsis. Crit Care Med 27: S4 (Abst)

    Google Scholar 

  32. Taylor F, Chang A, Ferrell G, et al (1991) C4b-binding protein exacerbates the host response to Escherichia coli. Blood 78:357–363

    PubMed  CAS  Google Scholar 

  33. de Jonge E, Dekkers PE, Creasey AA, et al (2000) Tissue factor pathway inhibitor dose-depen-dently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood 95:1124–1129

    PubMed  Google Scholar 

  34. Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze GJ Jr (1991) Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. Blood 78:387–393

    PubMed  CAS  Google Scholar 

  35. Sabharwal AK, Bajaj SP, Ameri A, et al (1995) Tissue factor pathway inhibitor and von Wille-brand factor antigen levels in adult respiratory distress syndrome and in a primate model of sepsis. Am J Respir Crit Care Med 151:758–767

    PubMed  CAS  Google Scholar 

  36. Day KC, Hoffman LC, Palmier MO, et al (1990) Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit. Blood 76:1538–1545

    PubMed  CAS  Google Scholar 

  37. Carr C, Bild GS, Chang AC, et al (1994) Recombinant E. coli-derived tissue factor pathway inhibitor reduces coagulopathic and lethal effects in the baboon gram-negative model of septic shock. Circ Shock 44:126–137

    PubMed  CAS  Google Scholar 

  38. Camerota AJ, Creasey AA, Patla V, Larkin VA, Fink MP (1998) Delayed treatment with recombinant human tissue factor pathway inhibitor improves survival in rabbits with gram-negative peritonitis. J Infect Dis 177:668–676

    Article  PubMed  CAS  Google Scholar 

  39. Kemme MJ, Burggraaf J, Schoemaker RC, et al (2000) The influence of reduced liver blood flow on the pharmacokinetics and pharmacodynamics of recombinant tissue factor pathway inhibitor. Clin Pharmacol Ther 67:504–511

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  41. Cirino G, Cicala C, Bucci M, et al (1997) Factor Xa as an interface between coagulation and inflammation. Molecular mimicry of factor Xa association with effector cell protease receptor-1 induces acute inflammation in vivo. J Clin Invest 99:2446–2451

    Article  PubMed  CAS  Google Scholar 

  42. Senden NH, Jeunhomme TM, Heemskerk JW, et al (1998) Factor Xa induces cytokine production and expression of adhesion molecules by human umbilical vein endothehal cells. J Immunol 161:4318–4324

    PubMed  CAS  Google Scholar 

  43. Johnson K, Choi Y, DeGroot E, Samuels I, Creasey A, Aarden L (1998) Potential mechanisms for a proinflammatory vascular cytokine response to coagulation activation. J Immunol 160: 5130–5135

    PubMed  CAS  Google Scholar 

  44. Kahn ML, Nakanishi-Matsui M, Shapiro MJ, Ishihara H, Coughlin SR (1999) Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 103: 879–887

    Article  PubMed  CAS  Google Scholar 

  45. Camerer E, Huang W, Coughlin SR (2000) Tissue factor-and factor X-dependent activation of protease-activated receptor 2 by factor Vila. Proc Natl Acad Sci USA 97:5255–5260

    Article  PubMed  CAS  Google Scholar 

  46. Taylor FBJ, Emerson TE J, Jordan R, Chang AK, Blick KE (1988) Antithrombin-III prevents the lethal effects of Escherichia coli infusion in baboons. Circ Shock 26:227–235

    PubMed  CAS  Google Scholar 

  47. Coalson JJ, Benjamin B, Archer LT, et al (1978) Prolonged shock in the baboon subjected to infusion of E. coh endotoxin. Circ Shock 5:423–437

    PubMed  CAS  Google Scholar 

  48. Taylor FBJ, Chang AC, Peer GT, et al (1991) DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage. Blood 78: 364–368

    PubMed  Google Scholar 

  49. Iampietro R, Souter P, Romisch J, Poole S, Gray E (2000) Antithrombin inhibits in vitro lipopoly-sacharide induced interleukin-6 production by suppression of mRNA. Intensive Care Med 26: S302 (Abst)

    Google Scholar 

  50. 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

    PubMed  CAS  Google Scholar 

  51. Hancock WW, Grey ST, Hau L, et al (1995) Binding of activated protein C to a specific receptor on human mononuclear phagocytes inhibits intracellular calcium signaling and monocyte-de-pendent proliferative responses. Transplantation 60:1525–1532

    Article  PubMed  CAS  Google Scholar 

  52. Grinnell BW, Hermann RB, Yan SB (1994) Human protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide. Glycobiol 4:221–225

    Article  CAS  Google Scholar 

  53. Taylor FBJ, Chang A, Hinshaw LB, Esmon CT, Archer LT, Beller BK (1984) A model for thrombin protection against endotoxin. Thromb Res 36:177–185

    Article  PubMed  CAS  Google Scholar 

  54. Comp PC, Jacocks RM, Ferrell GL, Esmon CT (1982) Activation of protein C in vivo. J Clin Invest 70:127–134

    Article  PubMed  CAS  Google Scholar 

  55. Cunningham MA, Romas P, Hutchinson P, Holdsworth SR, Tipping PG (1999) Tissue factor and factor VIIa receptor/ligand interactions induce proinflammatory effects in macrophages. Blood 94:3413–3420

    PubMed  CAS  Google Scholar 

  56. Randolph GJ, Luther T, Albrecht S, Magdolen V, Muller WA (1998) Role of tissue factor in adhesion of mononuclear phagocytes to and trafficking through endothelium in vitro. Blood 92: 4167–4177

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. E. de Jonge
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Levi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. van der Poll
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Intensive Care Erasme Hospital, Free University of Brussels, Route de Lennik 808, B-1070, Brussels, Belgium

    Jean-Louis Vincent (Head) (Head)

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

de Jonge, E., Levi, M., van der Poll, T. (2001). Natural Anticoagulants in Disseminated Intravascular Coagulation and Sepsis. In: Vincent, JL. (eds) Yearbook of Intensive Care and Emergency Medicine 2001. Yearbook of Intensive Care and Emergency Medicine 2001, vol 2001. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59467-0_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-59467-0_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-41407-0

  • Online ISBN: 978-3-642-59467-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation