, Volume 28, Issue 4, pp 237–244 | Cite as

Systemic Inflammation and Disseminated Intravascular Coagulation in Early Stage of ALI and ARDS: Role of Neutrophil and Endothelial Activation

  • Satoshi Gando
  • Takashi Kameue
  • Naoyuki Matsuda
  • Atsushi Sawamura
  • Mineji Hayakawa
  • Hirokatsu Kato


To determine the existence of a close link between inflammation and coagulation in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and to examine their prognostic value in the development of ARDS and clinical outcome, we made a prospective cohort study. The study subjects consisted of 57 patients: 19 patients with ARDS and 38 patients with ALI as defined by a Lung Injury Score of ≥2.5 and 1.0 to less than 2.5, respectively. According to the outcome, the patients were subdivided into the survivors and the nonsurvivors. Ten normal healthy volunteers served as control subjects. Plasma levels of soluble L-, P-, and E-selectins, intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), thrombomodulin (sTM), and neutrophil elastase were measured within 24 h after the diagnosis of ALI or ARDS. The number of systemic inflammatory response syndrome (SIRS) criteria being met by the patients and the disseminated intravascular coagulation (DIC) scores were determined simultaneously. The number of SIRS criteria and the DIC scores of the patients with ALI or ARDS showed high values, and more than half of the patients were complicated by DIC. The levels of sL-selectin in both groups of the patients were significantly lower than those of the control subjects. All other soluble adhesion molecules, neutrophil elastase, and sTM in the patients with ALI and ARDS were markedly elevated than those in the control subjects. The levels sICAM-1, sVCAM-1, and sTM in the ARDS patients significantly increased compared with the ALI patients. The number of SIRS criteria and the DIC scores in the nonsurvivors showed higher values than those in the survivors. In addition, we found significant differences in the levels of soluble adhesion molecules, neutrophil elastase, and sTM between the survivors and the nonsurvivors. {In conclusion, we found a concurrent activation of both inflammation and coagulation in the patients with ALI or ARDS. The results also suggest that systemic activation of inflammation and coagulation associated with endothelial injury has prognostic value for the development of ARDS and poor outcome.}

acute lung injury (ALI) acute respiratory distress syndrome (ARDS) coagulation inflammation neutrophil soluble adhesion molecules 


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  1. 1.
    Bernard, G. R., A. Artigas, K. L. Brigham, J. Carlet, K. Falke, L. Hudson, M. Lamy, J. R. Legall, A. Morris, R. Spragg, and the Consensus Committee. 1994. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am. J. Respir. Crit. Care Med. 149:818–824.Google Scholar
  2. 2.
    Moraes, T. J., C.W. Chow, and G. P. Downey. 2003. Proteases and lung injury. Crit. Care Med. 31[Suppl.]:S189–S194.Google Scholar
  3. 3.
    Abraham, E. 2003. Neutrophils and acute lung injury. Crit. Care Med. 31[Suppl.]:S195–S199.Google Scholar
  4. 4.
    McGill, S. N., N. A. Ahmed, and N.V. Christou. 1998. Endothelial cells: Role in infection and inflammation. World J. Surg. 22:171–178.Google Scholar
  5. 5.
    Weiss, S. J. 1989. Tissue destruction by neutrophils. N. Engl. J. Med. 320:365–376.Google Scholar
  6. 6.
    Abraham, E. 2000. Coagulation abnormalities in acute lung injury and sepsis. Am. J. Respir. Crit. Care Med. 22:401–404.Google Scholar
  7. 7.
    Idell, S. 2003. Coagulation, fibrinolysis, and fibrin deposition in acute lung injury. Crit. Care Med. 31[Suppl.]:S213–S220.Google Scholar
  8. 8.
    Kaplan, J. E. and A. B. Malik. 1987. Thrombin-induced intravas-cular coagulation: Role in vascular injury. Semin. Thromb. Hemost. 13:398–415.Google Scholar
  9. 9.
    Welty-Wolf, K. E., M. S. Carraway, T. L. Ortel, and C. A. Piantadosi. 2002. Coagulation and inflammation in acute lung injury. Thromb. Hemost. 88:17–25.Google Scholar
  10. 10.
    Donnely, S. C., C. Haslett, I. Dransfield, C. E. Robertson, D. C. Carter, J. A. Ross, and I. S. Grant. 1994. Role of selectins in devel-opment of adult respiratory distress syndrome. Lancet 344:215–219.Google Scholar
  11. 11.
    Bhatia, M. and S. Moochhala. 2004. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J. Pathol. 202:145–156.Google Scholar
  12. 12.
    Gando, S., T. Kameue, S. Nanzaki, T. Hayakawa, and Y. Nakanishi. 1997. Increased neutrophil elastase, persistent intravascular coag-ulation, and decreased fibrinolytic activity in patients with post-traumatic acute respiratory distress syndrome. J. Trauma 42:1068–1072.Google Scholar
  13. 13.
    Gando, S., S. Nanzaki, Y. Morimoto, S. Kobayashi, and O. Kemmotsu. 1999. Systemic activation of tissue-factor dependent co-agulation pathway in evolving acute respiratory distress syndrome in patients with trauma and sepsis. J. Trauma 47:719–723.Google Scholar
  14. 14.
    Gando, S., T. Kameue, N. Matsuda, M. Hayakawa, Y. Morimoto, T. Ishitani, and O. Kemmotsu. 2003. Imbalances between the levels of tissue factor and tissue factor pathway inhibitor in ARDS patients. Thromb. Res. 109:119–124.Google Scholar
  15. 15.
    Levi, M. and H. ten Cate. 1999. Disseminated intravascular coagulation. N. Engl. J. Med. 341:586–592.Google Scholar
  16. 16.
    Gando, S., T. Kameue, N. Matsuda, M. Hayakawa, T. Ishitani, Y. Morimoto, and O. Kemmotsu. 2002. Combined activation of co-agulation and inflammation has an important role in multiple organ dysfunction and poor outcome after severe trauma. Thromb. Hemost. 88:943–949.Google Scholar
  17. 17.
    Gando, S., T. Kameue, N. Matsuda, M. Hayakawa, H. Hoshino, and H. Kato. 2004. Serial changes in neutrophil-endothelial activation markers during the course of sepsis associated with disseminated intravascular coagulation. Thromb. Res. (in press).Google Scholar
  18. 18.
    Knauas, W. A., E. A. Draper, D. P. Wanger, and J. E. Zimmerman. 1985. APACHE II: A severity classification system. Crit. Care Med. 13:818–829.Google Scholar
  19. 19.
    Murray, J. F., M. A. Matthay, J. M. Luce, and M. R. Flick. 1988. An expanded definition of the adult respiratory distress syndrome. Am. Rev. Respir. Dis. 149:818–824.Google Scholar
  20. 20.
    Members of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee. 1992. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definition for sepsis and organ failure and guidelines for the use innovative therapies in sepsis. Crit. Care Med. 20:864–874.Google Scholar
  21. 21.
    Donnelly, S. C., I. MacGregor, A. Zamani, M. W. G. Gordon, C. E. Robertson, D. J. Steedman, K. Little, and C. Haslett. 1995. Plasma elastase levels and the development of the adult respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 151:1428–1433.Google Scholar
  22. 22.
    Bajaj, M. S., and S. M. Tricomi. 1999. Plasma levels of the three endothelial-specific proteins von Willebrand factor, tissue factor pathway inhibitor, and thrombomodulin do not predict the development of acute respiratory distress syndrome. Intensive Care Med. 25:1259–1266.Google Scholar
  23. 23.
    Rainer, T. H., N. Y. L. Lam, T. Y. F. Chan, and R. A. Cocks. 2000. Early role of neutrophil L-selectin in posttraumatic acute lung injury. Crit. Care Med. 28:2766–2772.Google Scholar
  24. 24.
    Bevilacqua, M. P., and M. Nelson. 1993. Selectins. J. Clin. Invest. 91:379–387.Google Scholar
  25. 25.
    Spertini, O., F. W. Luscinskas, G. S. Kansas, J. M. Munro, J. D. Griffin, M. A. Gimbrone, and T. F. Tedder. 1991. Leucocyte adhesion molecule-1 (LAM-1, L-selectin) interacts with inducible endothelial cell ligand to support leucocyte adhesion. J. Immunol. 147:2565–2573.Google Scholar
  26. 26.
    Sakamaki, F., A. Ishizuka, M. Handa, S. Fujishima, T. Urano, K. Sayama, H. Nakamura, M. Kanazawa, T. Kawashiro, M. Katayama, and Y. Ikeda. 1995. Soluble form of P-selectin in plasma is elevated in acute lung injury. Am. J. Respir. Crit. Care Med. 151:1821–1826.Google Scholar
  27. 27.
    Gearing, A. J. H. and W. Newman. 1993. Circulating adhesion molecules in disease. Immunol. Today 14:506–512.Google Scholar
  28. 28.
    Flori, H. R., L. B. Ware, D. Glidden, and M. A. Matthay. 2003. Early elevation of plasma soluble intercellular adhesion molecule-1 in pediatric acute lung injury identifies patients at increased risk of death and prolonged mechanical ventilation. Pediatr. Crit. Care Med. 4:315–321.Google Scholar
  29. 29.
    Neuman, S., G. Gunzer, N. Hennrich, and H. Lang. 1984. “PMN-elastase assay”: Enzyme immunoassay for human polymorph nuclear elastase complexed with alpha 1-proteinase inhibitor. J. Clin. Chem. Biochem. 22:693–697.Google Scholar
  30. 30.
    Ishii, H. and P. W. Majerus. 1985. Thrombomodulin is present in human plasma and urine. J. Clin. Invest. 22:693–697.Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Satoshi Gando
    • 1
  • Takashi Kameue
    • 1
  • Naoyuki Matsuda
    • 1
  • Atsushi Sawamura
    • 1
  • Mineji Hayakawa
    • 1
  • Hirokatsu Kato
    • 1
  1. 1.Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, HokkaidoUniversity Graduate School of MedicineSapporoJapan

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