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Blood, 15 December 2004, Vol. 104, No. 13, pp. 3958-3964. Prepublished online as a Blood First Edition Paper on August 19, 2004; DOI 10.1182/blood-2004-03-1203. This Article Full Text (PDF) All Versions of this Article: 2004-03-1203v1 104/13/3958    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liaw, P. C Y Articles by Cook, D. J Search for Related Content PubMed PubMed Citation Articles by Liaw, P. C Y Articles by Cook, D. J Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 30, 2004 Accepted July 30, 2004 Patients with severe sepsis vary markedly in their ability to generate activate protein C Patricia C Y Liaw*, Charles T Esmon, Kamyar Kahnamoui, Shelley Schmidt, Sarah Kahnamoui, Gary Ferrell, Suzanne Beaudin, Jim A Julian, Jeffrey I Weitz, Mark Crowther, Mark Loeb, and Deborah J Cook Department of Medicine, McMaster University, Hamilton, ON, Canada; Henderson Research Centre, Hamilton, ON, Canada Department of Biochemistry, McMaster University, Hamilton, ON, Canada Departments of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada Department of Surgery, McMaster University, Hamilton, ON, Canada Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Departments of Pathology, Biochemistry, Molecular Biology, University of Oklahoma Health Sciences Centre, Oklahoma City, OK, USA Howard Hughes Medical Institute, USA * Corresponding author; email: pliaw{at}thrombosis.hhscr.org. Activated protein C (APC) supplementation significantly reduces mortality in patients with severe sepsis, presumably by downregulating coagulation, inflammation, and apoptosis. In vivo, endogenous APC is generated from protein C (PC) "on demand" in response to elevated thrombin levels. Thrombomodulin and EPCR are endothelial receptors required to generate APC endogenously. Since these receptors may be downregulated in sepsis, we measured plasma markers of APC generation in 32 severe sepsis patients to determine whether APC generation is impaired, and whether markers of APC generation correlate with 28-day mortality. Relative to normals, all patients had elevated F1+2 and TAT levels (markers of thrombin generation and inhibition, respectively), and 28/32 patients had reduced PC levels. In 20 patients, APC levels paralleled elevated F1+2 levels, whereas 12 patients had low APC levels despite elevated F1+2 levels, suggesting that APC generation is impaired in the latter. No significant differences exist between survivors and non-survivors with respect to baseline PC levels, F1+2 levels, and APACHE II scores. Baseline APC levels were higher in survivors (p=0.024), and baseline F1+2/APC ratios were lower in survivors (p=0.047). Larger studies are warranted to establish whether APC generation profiles aid in managing sepsis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: APC: braking neutrophils to benefit patients? Joseph P. Mizgerd Blood 2004 104: 3841. [Full Text] [PDF] This article has been cited by other articles: L. J. Toltl, S. Beaudin, P. C. Liaw, and and the Canadian Critical Care Translational Biolo Activated Protein C Up-Regulates IL-10 and Inhibits Tissue Factor in Blood Monocytes J. Immunol., August 1, 2008; 181(3): 2165 - 2173. [Abstract] [Full Text] [PDF] M. Schouten, W. J. Wiersinga, M. Levi, and T. van der Poll Inflammation, endothelium, and coagulation in sepsis J. 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[Abstract] [Full Text] [PDF] X. Zheng, W. Li, J.-M. Gu, D. Qu, G. L. Ferrell, N. L. Esmon, and C. T. Esmon Effects of membrane and soluble EPCR on the hemostatic balance and endotoxemia in mice Blood, February 1, 2007; 109(3): 1003 - 1009. [Abstract] [Full Text] [PDF] P. Raivio, J. A. Fernandez, A. Kuitunen, J. H. Griffin, R. Lassila, and J. Petaja Activation of protein C and hemodynamic recovery after coronary artery bypass surgery J. Thorac. Cardiovasc. Surg., January 1, 2007; 133(1): 44 - 51. [Abstract] [Full Text] [PDF] R. Taneja and D. C. Cheng Con: Heparin-Bonded Cardiopulmonary Bypass Circuits Should Be Routine for All Cardiac Surgical Procedures Anesth. Analg., December 1, 2006; 103(6): 1370 - 1372. [Full Text] [PDF] J. A. Russell Management of Sepsis N. Engl. J. Med., October 19, 2006; 355(16): 1699 - 1713. [Full Text] [PDF] C. Feistritzer, R. A. Schuepbach, L. O. Mosnier, L. A. Bush, E. Di Cera, J. H. Griffin, and M. 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