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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 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 Citation Map 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. Search for Related Content PubMed PubMed Citation Articles by Liaw, P. C. Y. Articles by Cook, D. Related Collections Free Research Articles Clinical Trials and Observations Hemostasis, Thrombosis, and Vascular Biology Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Patients with severe sepsis vary markedly in their ability to generate activated 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 Cook From the Departments of Medicine, Biochemistry, Clinical Epidemiology and Biostatistics, Surgery, and Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, and the Henderson Research Centre, Hamilton, Ontario, and the Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, and the Departments of Pathology, and Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, and the Howard Hughes Medical Institute, Oklahoma City, OK. Activated protein C (APC) supplementation significantly reduces mortality in patients with severe sepsis, presumably by down-regulating coagulation, inflammation, and apoptosis. In vivo, endogenous APC is generated from protein C (PC) "on demand" in response to elevated thrombin levels. Thrombomodulin and endothelial cell protein C receptor are endothelial receptors required to generate APC endogenously. Since these receptors may be down-regulated in sepsis, we measured plasma markers of APC generation in 32 patients with severe sepsis 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 thrombin-antithrombin complex (TAT) levels (markers of thrombin generation and inhibition, respectively), and 28 of 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 nonsurvivors with respect to baseline PC levels, F1 + 2 levels, and APACHE II (acute physiology and chronic health evaluation) scores. Baseline APC levels were higher in survivors (P = .024), and baseline F1 + 2/APC ratios were lower in survivors (P = .047). Larger studies are warranted to establish whether APC generation profiles aid in managing sepsis. (Blood. 2004;104:3958-3964) 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: M. Schouten, W. J. Wiersinga, M. Levi, and T. van der Poll Inflammation, endothelium, and coagulation in sepsis J. Leukoc. Biol., March 1, 2008; 83(3): 536 - 545. [Abstract] [Full Text] [PDF] C. E. Ventetuolo and M. M. Levy Sepsis: A Clinical Update Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(2): 571 - 577. [Full Text] [PDF] D. Borgel, C. Bornstain, P. H. Reitsma, N. Lerolle, S. Gandrille, F. Dali-Ali, C. T. Esmon, J.-Y. Fagon, M. Aiach, and J.-L. Diehl A Comparative Study of the Protein C Pathway in Septic and Nonseptic Patients with Organ Failure Am. J. Respir. Crit. 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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. Riewald Protective Signaling by Activated Protein C Is Mechanistically Linked to Protein C Activation on Endothelial Cells J. Biol. Chem., July 21, 2006; 281(29): 20077 - 20084. [Abstract] [Full Text] [PDF] K. Yano, P. C. Liaw, J. M. Mullington, S.-C. Shih, H. Okada, N. Bodyak, P. M. Kang, L. Toltl, B. Belikoff, J. Buras, et al. Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality J. Exp. Med., June 12, 2006; 203(6): 1447 - 1458. [Abstract] [Full Text] [PDF]

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