Changes in the coagulation-fibrinolysis balance of endothelial cells and mononuclear phagocytes: role in disseminated intravascular coagulation associated with infectious diseases

  • Nicola Semeraro
  • Mario Colucci


Over the last few years, evidence has accumulated that the pathogenetic mechanism of disseminated intravascular coagulation encountered in patients with infectious diseases is extraordinarily complex and involves multiple interactions between the microorganism itself and/or a number of mediators, both microorganism derived and host manufactured, and multifunctional cellular systems, namely endothelial cells and mononuclear phagocytes. In particular, infectious agents and mediators shift the coagulation-fibrinolysis equilibrium of these cells towards fibrin formation and accumalation, via enhancement of procoagulant and fibrinolytic capacities. New insights into the pathogenetic mechanism may have important implications for the management of infected patients with disseminated intravascular coagulation.

Key words

Disseminated intravascular coagulation Infection Coagulation-fibrinolysis Endothelial cells Mononuclear phagocytes 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Almdahl SM, Brox JH, Osterud B, Mononclear phagocyte thromboplastin and endotoxin in patients with secondary peritonities. Scand J Gastroenterol 22: 914, 1987PubMedCrossRefGoogle Scholar
  2. 2.
    Astedt B, Lecander I, Ny T, The placental type plasminogen activator inhibitor, PAI-2. Fibrinolysis 1: 203, 1987CrossRefGoogle Scholar
  3. 3.
    Bachman F, Fibrinolysis. In: Verstraete M, Vermylen J, Lijnen HR, Arnout J (eds) Thrombosis and haemostasis. Leuven University Press, Leuven, pp 227–265, 1987.Google Scholar
  4. 4.
    Bauer KA, Cate H ten, Barzegar S, Springgs DR, Sherman ML, Rosenberg RD, Tumor necrosis factor infusions have a procoagulant effect on the hemostatic mechanism in humans. Blood 74: 165, 1989PubMedGoogle Scholar
  5. 5.
    Baumgartner JD, Monoclonal anti-endotoxin antibodies for the treatment of gram-negative bacteremia and septic shock. Eur J Clin Microbiol Infect Dis 9: 711, 1990PubMedCrossRefGoogle Scholar
  6. 6.
    Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran R, Gimbrone M, Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin-1. Proc Natl Acad Sci USA 83: 4533, 1986PubMedCrossRefGoogle Scholar
  7. 7.
    Blasi F, Surface receptors for urokinase plasminogen activator. Fibrinolysis 2: 73, 1988CrossRefGoogle Scholar
  8. 8.
    Brandtzaeg P, Joo GB, Brusletto B, Kierulf P, Plasminoge activator inhibitor 1 and 2, alpha-2-antiplasmin, plasminogen, and endotoxin levels in systemic meningococcal disease. Thromb Res 57:271, 1990PubMedCrossRefGoogle Scholar
  9. 9.
    Brukman J, Wiggins RC Procoagulant activity in kidneys of normal and bacterial lipopolysaccharide-treated rabbits. Kidney Int 32: 31, 1987PubMedCrossRefGoogle Scholar
  10. 10.
    Castellote JC, Grau E, Linde MA, Pujol-Moix N, Rutllant MLI, Detection of both type 1 and type 2 plasminogen activator inhibitors in human monocytes. Thromb Haemost 63: 67, 1990PubMedGoogle Scholar
  11. 11.
    Chapman HA, Vavrin Z, Hibbs JB Jr, Coordinate expression of macrophage procoagulant and fibrinolytic activity in vitro and in vivo. J Immunol 130: 261, 1983.PubMedGoogle Scholar
  12. 12.
    Chapman HA, Yang X, Sailor LZ, Sugarbaker DJ, Developmental expression of plasminogen activator inhibitor type 1 by human alveolar macrophages. J Immunol 145: 3398, 1990PubMedGoogle Scholar
  13. 13.
    Colman RV, Contact system in infectious disease. Rev Infect Dis 11 [Suppl 4]: S689, 1989.Google Scholar
  14. 14.
    Colucci M, Balconi G Lorenzet R, Pietra A, Locati D, Donati MB, Semeraro N, Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 71: 1893, 1983.PubMedCrossRefGoogle Scholar
  15. 15.
    Colucci M, Paramo JA, Collen D, Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 75: 818, 1985PubMedCrossRefGoogle Scholar
  16. 16.
    Colucci M, Paramo JA, Stassen JM, Collen D, Influence of the fast-acting inhibitor of plasminogen activator on in vivo thrombolysis induced by tissue plasminogen activator in rabbits. J Clin Invest 78: 138, 1986PubMedCrossRefGoogle Scholar
  17. 17.
    Colucci M, Altomare DF, Chetta G, Triggiani R, Cavallo LG, Semeraro N, Impaired fibrinolysis in obstructive jaundice. Evidence from clinical and experimental studies. Thromb Haemost 60: 25, 1988PubMedGoogle Scholar
  18. 18.
    Conkling PR, Chua CC, Nadler P, Greenberg CS, Doty E, Misukonis MA, Haney AF, Bast RC, Jr, Weinberg JB, Clinical trials with human tumor necrosis factor: in vivo and in vitro effects on human mononuclear phagocyte function. Cancer Res 48: 5604, 1988PubMedGoogle Scholar
  19. 19.
    Conkling PR, Greenberg CS, Weinberg JB, Tumor necrosis factor induces tissue factor-like activity in human leukemia cell line U937 and peripheral blood monocytes. Blood 72: 128, 1988PubMedGoogle Scholar
  20. 20.
    Dejana E, Breviario F, Erroi A, Bussolino F, Mussoni L, Gramse L, Pintucci G, Casali B, Dinarello LA Damme J van, Mantovani A, Modulation of endothelial cell functions by different molecular species of interleukin 1. Blood 69: 695, 1987PubMedGoogle Scholar
  21. 21.
    Drake TA, Morissey JW, Edgington TS, Selective cellular expression of tissue factor in human tissues. Am J Pathol 134: 1087, 1989PubMedGoogle Scholar
  22. 22.
    Drancourt M, Alessi MC, Levy PY, Juhan-Vague I, Raoult D, Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor byRickettsia conorii- andRickettsia rickettsii-infected cultured endothelial cells. Infect Immun 58: 2459, 1990PubMedGoogle Scholar
  23. 23.
    Edgington TS, Machman N, Brand K, Ruf W, The structural biology of expression and function of tisdue factor. Thromb Haemost 66: 67, 1991PubMedGoogle Scholar
  24. 24.
    Edwards RL, Rickles FR, Macrophage procoagulants. In: Spaet TH (ed) Progress in hemostasis and thrombosis, vol. 7. Grune & Stratton, New York, pp 183–201, 1984Google Scholar
  25. 25.
    Estelles A, Andres C, Gilabert J, Espana F, Hendl S, Aznar J, Inibidores de los activadores del plasminogeno (PAI-1 y PAI-2). Aspectos fisiopatologicos. Rev Iberoamer Tromb Hemostassia 3–4: 18, 1989Google Scholar
  26. 26.
    Fong Y, Lowry SF, Tumor necrosis factor in the pathophysiology of infection and sepsis. Clin Immunol Immunopathol 55: 157, 1990PubMedCrossRefGoogle Scholar
  27. 27.
    Garner R, Evensen SA, Endotoxin-induced intravascular coagulation and shock in dogs: the role of factor VII. Br J Haematol 27: 655, 1974PubMedCrossRefGoogle Scholar
  28. 28.
    Hamilton KK, Hattori R, Esmon CT, Sims PJ, Complement proteins C5b-9 induce vesiculations of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. J Biol Chem 265: 3809, 1990PubMedGoogle Scholar
  29. 29.
    Hinsberg VWM van, Regulation of the synthesis and secretion of plasminogen activators by endothelial cells. Haemostasis 18: 307, 1988Google Scholar
  30. 30.
    Hinsberg VWM van, Kooistra T, Berg EA van den, Princen HMG, Fiers W, Emeis JJ, Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo. Blood 72: 1467, 1988Google Scholar
  31. 31.
    Hofmann H, Mahn I, Muller-Berghaus G, The generation of microclots from circulating soluble Des-A fibrin. Thromb Haemost 42: 39a, 1979Google Scholar
  32. 32.
    Idell S, James KK, Levin EG, Schwartz BS, Manchanda N, Maunder RJ, Martin TR, McLarty J, Fair DS, Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in adult respiratory distres syndrome. J Clin Invest 84: 695, 1989PubMedCrossRefGoogle Scholar
  33. 33.
    Kobayashi M, Shimada K, Onawa T, Human recombinant interleukin 1β- and tumor necrosis factor α-mediated suppression of heparin-like compounds on cultured porcine aortic endothelial cells. J Cell Physiol 144: 383, 1990PubMedCrossRefGoogle Scholar
  34. 34.
    Krishnamurti C, Barr CF, Hassett MA, Young GD, Alving BM, Plasminogen activator inhibitor: a regulator of ancrod-induced fibrin deposition in rabbits. Blood 69: 798, 1987PubMedGoogle Scholar
  35. 35.
    Krishnamuri T, Alving B, Effect of dengue virus on procoagulant and fibrinolytic activities of monocytes. Rev Infect Dis 11 [Suppl 4]: S843, 1989Google Scholar
  36. 36.
    Levy G, Abecassis M Activation of the immune coagulation system by murine hepatitis virus strain 3. Rev Infect Dis 11 [Suppl 4]: S712, 1989Google Scholar
  37. 37.
    Loskutoff DJ, Sawdey M, Mimuro J. Type 1 plasminogen activator inhibitor. In: Coller BS (ed) Progress in hemostasis and thrombosis, vol 9. Saunders, Philadelphia, pp 87–115, 1989Google Scholar
  38. 38.
    Marder VJ, Martin SE, Francis CV, Colman RV, Consumptive thrombohemorrhagic disorders. In: Colman RV, Hirsh J, Marder VJ, Salzman EW (eds) Hemostasis and thrombosis. Basic principles and clinical practice. Lippincott, Philadelphia, pp 975–1015, 1987Google Scholar
  39. 39.
    Margaretten W, Zunker HO, McKay DG, Production of the generalized Shwartzman reaction in pregnant rats by intravenous infusion of thrombin. Lab Invest 13: 552, 1964PubMedGoogle Scholar
  40. 40.
    Moore KL, Andreoli SP, Esmon NL, Esmon CT, Bang NU, Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. J Clin Invest 79: 124, 1987PubMedCrossRefGoogle Scholar
  41. 41.
    Muller-Berghaus G, The role of platelets, leukoccytes and complement in the activation of intravascular coagulation by endotoxin. In: Gaetano G de, Garattini S (eds) Platelets: a multidisciplinary approach. Raven, New York, pp 303–320, 1978Google Scholar
  42. 42.
    Niemetz J, The role of leukocytes in thrombosis. In: Colman RV, Hirsh J, Marder VJ, Salzman EW (eds) Hemostasis and thrombosis. Basic principles and clinical practice. Lippincott, Philadelphia, pp 1089–1097, 1987Google Scholar
  43. 43.
    Ogawa S, Gerlach H, Esposito C, Pasagian-Macaulay A, Brett J, Stern D, Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. J Clin Invest 85: 1090, 1990.PubMedCrossRefGoogle Scholar
  44. 44.
    Osterud B, Flaegstad T, Increased thromboplastin activity in monocytes of patients with meningococcal infections: related to unfavourable prognosis. Thromb Haemost49: 5, 1983PubMedGoogle Scholar
  45. 45.
    Paramo JA, Perez JL, Serrano M, Rocha E, Types 1 and 2 plasminogen activator inhibitor and tumor necrosis factor alpha in patients with sepsis. Thromb Haemost 64: 3, 1990PubMedGoogle Scholar
  46. 46.
    Poll T van der, Buller HR, Cate H ten, Wortel CH, Bauer KA, Deventer SJH van, Hack CE, Sauerwein HP, Rosenberg AD, Cate JW ten, Activation of coagulation after administration of TNF to normal subjects. N Engl J Med 322: 1622, 1990PubMedCrossRefGoogle Scholar
  47. 47.
    Pralong G, Calandra T, Glauser MP, Schellekens J, Verhoef J, Bachmann F, Kruithof EKO, Plasminogen activator inhibitor 1: a new prognostic marker in spetic shock. Thromb Haemost 61: 459, 1989PubMedGoogle Scholar
  48. 48.
    Preissner KT, Anticoagulant potential of endothelial cell membrane components. Haemostasis 18: 271, 1988PubMedGoogle Scholar
  49. 49.
    Rothberger H, Dove FB, Lee TK, McGee MP, Kardon B, Procoagulant activity of lymphocyte-macrophage populations in rabbits: selective increases in marrow, blood and spleen cells during Shwartzman reactions. Blood 61: 712, 1983PubMedGoogle Scholar
  50. 50.
    Sawdey M, Podor TJ, Loskutoff DJ, Regulation of type 1 plasminogen activator inhibitor gene expression in cultured bovine aortic endothelial cells. J Biol Chem 264: 10396, 1989PubMedGoogle Scholar
  51. 51.
    Scarpati EM, Sadler JE, Regulation of endothelial cell coagulant properties. J Biol Chem 264: 20705, 1989PubMedGoogle Scholar
  52. 52.
    Schwartz BS, Monroe MC, Levin EG. Increased release of plasminogen activator inhibitor type 2 accompanies the human mononuclear cell tissue factor response to lipopolysaccharide. Blood 71: 734, 1989Google Scholar
  53. 53.
    Semeraro N, Biondi A, Lorenzet R, Locati D, Mantovani A, Donati MB, Direct induction of tissue factor synthesis by endotoxin in human macrophages from diverse anatomical sites. Immunology 50: 529, 1983PubMedGoogle Scholar
  54. 55.
    Semeraro N, Montermurro P, Rossiello MR, Colucci M, Involvement of leukocytes in haemostasis and thrombosis. In: Barbui T, Cortelazzo S, Viero P, Gorini S, Gaetano G de (eds) Cellular blood components in haemostasis and thrombosis. Libbey, London pp 81–95, 1988Google Scholar
  55. 56.
    Semeraro N, Montemurro P, Chetta G, Altomare DF, Giordano D, Colucci M, Increased procoagulant activity of peripheral blood monocytes in human and experimental obstructive jaundice. Gastroenterology 96: 892, 1989PubMedGoogle Scholar
  56. 57.
    Semeraro N, Montemurro P, Triggiani R, Conese M, Cavallo LG, Colucci M, Endothelial procoagulant and thrombomodulin activity in endotoxin-treated rabbits. Thromb Haemost 65: 794, 1991Google Scholar
  57. 58.
    Shen SMC, Rapaport SI, Feinstein DI, Intravascular clotting after endotoxin in rabbits with impaired intrinsic clotting produced by a factor VIII antibody. Blood 42: 523, 1973PubMedGoogle Scholar
  58. 59.
    Silva AT, Bayston KF, Cohen J, Propyylactic and therapeutic effects of a monoclonal antibody to tumor necrosis factor-alpha in experimental gram-negative shock. J Infect Dis 162: 421, 1990PubMedGoogle Scholar
  59. 60.
    Stern DM, Kaiser E, Nawroth PP, Regulation of the coagulation system by vascular endothelial cells. Haemostasis 18: 202, 1988PubMedGoogle Scholar
  60. 61.
    Suffredini AF, Harpel PC, Parrillo JE, Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. N Engl J Med 320: 1165, 1989PubMedCrossRefGoogle Scholar
  61. 62.
    Taylor FB Jr, Chang A, Ruf W, Morissey JH, Catlett R, Blick K, Edgington TS, LethalE. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 33: 127, 1991PubMedGoogle Scholar
  62. 63.
    Thomas L, Good RA, Studies on the generalized Shwartzman reaction. J Exp Med 96: 605, 1952PubMedCrossRefGoogle Scholar
  63. 64.
    Van Deventer SJH, Buller HR, Cate ten JW, Aarden LA, Hack CE, Sturk A, Experiment endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic and complement pathways. Blood 76: 2520, 1999Google Scholar
  64. 65.
    Vercellotti JM, Proinflammatory and procoagulant effects of herpes simplex infection on human endothelium. Blood Cells 16: 209, 1990PubMedGoogle Scholar
  65. 66.
    Warr TA, Rao LVM, 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 75: 1481, 1990PubMedGoogle Scholar
  66. 67.
    Wilcox JN, Smith KM, Schwartz SM, Gordon D, Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci USA 86: 2839, 1989PubMedCrossRefGoogle Scholar
  67. 68.
    Wohlwend A, Belin D, Vassalli JD, Plasminogen activator-specific inhibitor produced by human monocytes macrophages. J Exp Med 165: 320, 1987PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Nicola Semeraro
    • 1
  • Mario Colucci
    • 1
  1. 1.Dipartimento di Scienze Biomediche e Oncologia Umana Sezione di Patologia Generale e Oncologia SperimentaleUniversity of BariBariItaly

Personalised recommendations