Journal of Critical Care
Volume 26, Issue 6 , Pages 539-545 , December 2011

Severe protein C deficiency is associated with organ dysfunction in patients with severe sepsis

  • Andrew D. Shaw, MB

      Affiliations

    • Department of Anesthesiology, Duke University, DUMC 3094, Durham, NC 27710, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 919 286 6938; fax: +1 919 286 6853.
    • ,
  • George M. Vail, MD

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    • ,
  • Douglas J. Haney, PhD

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    • ,
  • Jin Xie, MS

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    • ,
  • Mark D. Williams, MD

      Affiliations

    • Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA

References 

  1. Esper A, Martin GS. Is severe sepsis increasing in incidence and severity?. Crit Care Med. 2007;35:1414–1415
  2. Angus DC, Linde-Zwirble WT, Lidicker J, et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–1310
  3. Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348:1546–1554
  4. Dhainaut JF, Yan SB, Margolis BD, et al. Drotrecogin alfa (activated) (recombinant human activated protein C) reduces host coagulopathy response in patients with severe sepsis. Thromb Haemost. 2003;90:642–653
  5. Kinasewitz GT, Yan SB, Basson B, et al. Universal changes in biomarkers of coagulation and inflammation occur in patients with severe sepsis, regardless of causative micro-organism. [ISRCTN74215569] Crit Care. 2004;8:R82–R90
  6. Macias WL, Nelson DR. Severe protein C deficiency predicts early death in severe sepsis. Crit Care Med. 2004;32:S223–S228
  7. Shorr AF, Bernard GR, Dhainaut JF, et al. Protein C concentrations in severe sepsis: an early directional change in plasma levels predicts outcome. Crit Care. 2006;10:R92
  8. Esmon CT. Inflammation and the activated protein C anticoagulant pathway. Semin Thromb Hemost. 2006;32:49–60
  9. Faust SN, Levin M, Harrison OB, et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med. 2001;345:408–416
  10. Hensley LE, Stevens EL, Yan SB, et al. Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever. J Infect Dis. 2007;196:5390–5399
  11. Fourrier F, Chopin C, Goudemand J, et al. Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C, and protein S deficiencies. Chest. 1992;101:816–823
  12. Borgel D, Bornstain C, Reitsma PH, et al. A comparative study of the protein C pathway in septic and non-septic patients with organ failure. Am J Respir Crit Care Med. 2007;176:878–885
  13. Dettenmeier P, Swindell B, Stroud M, et al. Role of activated protein C in the pathophysiology of severe sepsis. Am J Crit Care. 2003;12:518–524
  14. Joyce DE, Nelson DR, Grinnell BW. Leukocyte and endothelial cell interactions in sepsis: relevance of the protein C pathway. Crit Care Med. 2004;32:S280–S286
  15. Brunkhorst F, Sakr Y, Hagel S, et al. Protein C concentrations correlate with organ dysfunction and predict outcome independent of the presence of sepsis. Anesthesiology. 2007;107:15–23
  16. Mesters RM, Helterbrand J, Utterback BG, et al. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications. Crit Care Med. 2000;28:2209–2216
  17. Shorr AF, Nelson DR, Wyncoll DL, et al. Protein C: a potential biomarker in severe sepsis and a possible tool for monitoring treatment with drotrecogin alfa (activated). Crit Care. 2008;12:R45
  18. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699–709
  19. Ferreira FL, Bota DP, Bross A, et al. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286:1754–1758
  20. Esmon CT. The protein C pathway. Chest. 2003;124:26S–32S
  21. Murakami K, Okajima K, Uchiba M, et al. Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production. Am J Physiol. 1997;272:L197–L202
  22. Robriquet L, Collet F, Tournoys A, et al. Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response. Respir Res. 2006;7:41
  23. Maybauer MO, Maybauer DM, Fraser JF, et al. Recombinant human activated protein C improves pulmonary function in ovine acute lung injury resulting from smoke inhalation and sepsis. Crit Care Med. 2006;34:2432–2438
  24. Richard JC, Bregeon F, Leray V, et al. Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury. Intensive Care Med. 2007;33:2199–2206
  25. Laszik Z, Mitro A, Taylor FB, et al. Human protein C receptor is present primarily on endothelium of large blood vessels: implications for the control of the protein C pathway. Circulation. 1997;96:3633–3640
  26. Finigan JH, Dudek SM, Singleton PA, et al. Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. J Biol Chem. 2005;280:17286–17293
  27. Han WK, Waikar SS, Johnson A, et al. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int. 2008;73:863–869
  28. Dent CL, Ma Q, Dastrala S, et al. Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study. Crit Care. 2007;11:R127
  29. Bennett M, Dent CL, Ma Q, et al. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clin J Am Soc Nephrol. 2008;3:665–673
  30. Bouchard J, Malhotra R, Shah S, et al. Protein C: a potential biomarker for acute kidney injury? Canadian Society of Nephrology annual meeting, abstract no. 61, 2010. Available at http://www.csnscn.ca/local/files/2010%20Annual%20Meeting%20Final%20Program%20with%20Cover.pdfAccessed on November 2010

☆ Financial support: This work was sponsored by Eli Lilly and Company.

☆☆ Competing interests: Author Ms. Xie is employed by and is a stockholder in Eli Lilly and Company. Drs. Vail, Haney, and Williams are previous employees of Eli Lilly and Company. Dr. Shaw has received speaker bureau and advisory board fees from Eli Lilly and Company.

PII: S0883-9441(11)00208-5

doi: 10.1016/j.jcrc.2011.05.006

Journal of Critical Care
Volume 26, Issue 6 , Pages 539-545 , December 2011

Article Tools

* Image Usage & Resolution