Coagulopathy and the role of recombinant human activated protein C in sepsis and following polytrauma

Bibliography

• SHACKFORD SR, MACKERSIE RC, HOLBROOK TL et al.: The epidemiology of traumatic death. A population based analysis. Arch. Surg. (1993) 128:571-575.
   PubMed Web of Science ®Google Scholar
• TRUNKEY D: Trauma. Accidental and intentional injuries account for more years of life lost in the US than cancer and heart disease. Among the prescribed remedies are improved preventive efforts, speedier surgery and further research. Sci. Am. (1983) 249(2):28-35.
   PubMed Web of Science ®Google Scholar
• ANDERSON RN, MININO AM, FINGERHUT LA, WARNER M, HEINEN MA: Deaths: injuries, 2001. Natl. Vital Stat. Rep. (2004) 52(21):1-86.
   PubMedGoogle Scholar
• FAIST E, BAUE AE, DITTMER H, HEBERER G: Multiple organ failure in polytrauma patients. J. Trauma (1983) 23(9):775-787.
   PubMed Web of Science ®Google Scholar
• CRUMP JM, DUNCAN DA, WEARS R: Analysis of multiple organ system failure in trauma and nontrauma patients. Am. Surg. (1988) 54(12):702-708.
   PubMed Web of Science ®Google Scholar
• REGEL G, LOBENHOFFER P, GROTZ M, PAPE HC, LEHMANN U, TSCHERNE H: Treatment results of patients with multiple trauma: an analysis of 3406 cases treated between 1972 and 1991 at a German Level I Trauma Center. J. Trauma (1995) 38(1):70-78.
   PubMed Web of Science ®Google Scholar
• PAPE H, STALP M, DAHLWEID M, REGEL G, TSCHERNE H: [Optimal duration of primary surgery with regards to a ‘Borderline’-situation in polytrauma patients. Arbeitsgemeinschaft ‘Polytrauma’ der Deutschen Gesellschaft fur Unfallchirurgie]. Unfallchirurg (1999) 102(11):861-869.
   PubMed Web of Science ®Google Scholar
• NAST-KOLB D, AUFMKOLK M, RUCHOLTZ S, OBERTACKE U, WAYDHAS C: Multiple organ failure still a major cause of morbidity but not mortality in blunt multiple trauma. J. Trauma (2001) 51(5):835-841.
   PubMed Web of Science ®Google Scholar
• GORIS RJ, TE BOEKHORST TP, NUYTINCK JK, GIMBRERE JS: Multiple-organ failure. Generalized autodestructive inflammation? Arch. Surg. (1985) 120(10):1109-1115.
   PubMed Web of Science ®Google Scholar
• SAUAIA A, MOORE FA, MOORE EE, NORRIS JM, LEZOTTE DC, HAMMAN RF: Multiple organ failure can be predicted as early as 12 hours after injury. J. Trauma (1998) 45(2):291-301.
   PubMed Web of Science ®Google Scholar
• DURHAM RM, MORAN JJ, MAZUSKI JE, SHAPIRO MJ, BAUE AE, FLINT LM: Multiple organ failure in trauma patients. J. Trauma (2003) 55(4):608-616.
   PubMed Web of Science ®Google Scholar
• ANGUS DC, LINDE-ZWIRBLE WT, LIDICKER J, CLERMONT G, GARCILLO J, PINSKY MR: Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome and associated cost of care. Crit. Care Med. (2001) 29:1303-1310.
   PubMed Web of Science ®Google Scholar
• ENDERSON BL, CHEN JP, ROBINSON R, MAULL KI: Fibrinolysis in multisystem trauma patients. J. Trauma (1991) 31(9):1240-1246.
   PubMed Web of Science ®Google Scholar
• GEERTS WH, CODE KI, JAY RM, CHEN E, SZALAI JP: A prospective study of venous thromboembolism after major trauma. N. Engl. J. Med. (1994) 331(24):1601-1606.
   PubMed Web of Science ®Google Scholar
• ENGELMAN DT, GABRAM SG, ALLEN L, ENS GE, JACOBS LM: Hypercoagulability following multiple trauma. World J. Surg. (1996) 20:5-10.
   PubMed Web of Science ®Google Scholar
• GANDO S, NANZAKI S, KEMMOTSU O: Coagulofibrinolytic changes after isolated head injury are not different from those in trauma patients without head injury. J. Trauma (1999) 46(6):1070-1076.
   PubMed Web of Science ®Google Scholar
• SCHREIBER MA, DIFFERDING J, THORBORG P, MAYBERRY JC, MULLINS RJ: Hypercoagulability is most prevalent early after injury and in female patients. J. Trauma (2005) 58(3):475-480.
   PubMed Web of Science ®Google Scholar
• MEISSNER MH, CHANDLER WL, ELLIOTT JS: Venous thromboembolism in trauma: a local manifestation of systemic hypercoagulability? J. Trauma (2003) 54(2):224-231.
   PubMed Web of Science ®Google Scholar
• FLUTE PT: Coagulation and fibrinolysis after injury. J. Clin. Pathol. Suppl. (R Coll. Pathol). (1970) 4:102-109.
   Google Scholar
• SCHMIDT U, ENDERSON BL, CHEN JP, MAULL KI: D-dimer levels correlate with pathologic thrombosis in trauma patients. J. Trauma (1992) 33(2):312-319.
   PubMed Web of Science ®Google Scholar
• CAPORALE A, TIRINDELLI MC, AURELLO P et al.: Evaluation of postoperative blood coagulation changes in elderly patients undergoing major surgery. Ital. J. Surg. Sci. (1989) 19(1):51-56.
   PubMedGoogle Scholar
• ATTAR S, BOYD D, LAYNE E, MCLAUGHLIN J, MANSBERGER AR, COWLEY RA: Alterations in coagulation and fibrinolytic mechanisms in acute trauma. J. Trauma (1969) 9(11):939-965.
   PubMed Web of Science ®Google Scholar
• STEIN SC, CHEN XH, SINSON GP, SMITH DH: Intravascular coagulation: a major secondary insult in nonfatal traumatic brain injury. J. Neurosurg. (2002) 97(6):1373-1377.
   PubMed Web of Science ®Google Scholar
• PIEK J, CHESNUT RM, MARSHALL LF et al.: Extracranial complications of severe head injury. J. Neurosurg. (1992) 77(6):901-907.
   PubMed Web of Science ®Google Scholar
• SCHERER RU, SPANGENBERG P: Procoagulant activity in patients with isolated severe head trauma. Crit. Care Med. (1998) 26:149-156
   PubMed Web of Science ®Google Scholar
• HULKA F, MULLINS RJ, FRANK EH: Blunt brain injury activates the coagulation process. Arch. Surg. (1996) 131:923-928
   PubMed Web of Science ®Google Scholar
• KEIMOWITZ RM, ANNIS BL: Disseminated intravascular coagulation associated with massive brain injury. J. Neurosurg. (1973) 39(2):178-180.
   PubMed Web of Science ®Google Scholar
• BECKER S, SCHNEIDER W, KREUZ W, JACOBI G, SCHARRER I, NOWAK-GOTTL U: Post-trauma coagulation and fibrinolysis in children suffering from severe cerebro-cranial trauma. Eur. J. Pediatr. (1999) 158(Suppl. 3):S197-S202.
   PubMed Web of Science ®Google Scholar
• MINER ME, KAUFMAN HH, GRAHAM SH, HAAR FH, GILDENBERG PL: Disseminated intravascular coagulation fibrinolytic syndrome following head injury in children: frequency and prognostic implications. J. Pediatr. (1982) 100(5):687-691.
   PubMed Web of Science ®Google Scholar
• PADKIN A, GOLDFRAD C, BRADY AR, YOUNG D, BLACK N, ROWAN K: Epidemiology of severe sepsis occurring in the first 24 hours in ICU in England, Wales and Northern Ireland. Crit. Care Med. (2003) 31:2332-2338.
   PubMed Web of Science ®Google Scholar
• ALBERTI C, BRUN-BUISSON C, BURCHARDI H et al.: Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. (2002) 28:108-121.
   PubMed Web of Science ®Google Scholar
• BONE RC, BALK RA, CERRA FB et al.: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest (1992) 101:1644-1655.
   PubMed Web of Science ®Google Scholar
• DE JONGE E, DEKKERS PE, CREASEY AA et al.: Tissue factor pathway inhibitor dose-dependently inhibits coagulation activation without influencing the fibrinolytic and cytokine response during human endotoxemia. Blood (2000) 95(4):1124-1129.
   PubMed Web of Science ®Google Scholar
• GREEN C, DINNES J, TAKEDA A et al.: Clinical effectiveness and cost-effectiveness of drotrecogin alfa (activated) (Xigris®) for the treatment of severe sepsis in adults: a systematic review and economic evaluation. Health Technol. Assess. (2005) 9(11):3-140.
   Google Scholar
• YAN SB, HELTERBRAND JD, HARTMAN DL, WRIGHT TJ, BERNARD GR: Low levels of protein C are associated with poor outcome in severe sepsis. Chest (2001) 120:915-922.
   PubMed Web of Science ®Google Scholar
• FOURRIER F: Recombinant human activated protein C in the treatment of severe sepsis: an evidence-based review. Crit. Care Med. (2004) 32(Suppl. 11):534-541.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• BERNARD GR, VINCENT JL, LATERRE PF et al.: Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group: Efficacy and safety of recombinant human activated protein C for severe sepsis. N. Engl. J. Med. (2001) 344(10):699-709.
   PubMed Web of Science ®Google Scholar
• ANTI-INFECTIVE ADVISORY COMMITTEE: FDA Clinical Review: Drotrecogin alfa (activated) [recombinant human activated protein C (rhAPC)] Xigris®, BLA # 125029/0. Rockville, MD: Food and Drug Administration (2002).
   Google Scholar
• EUROPEAN AGENCY FOR EVALUATION OF MEDICINAL PRODUCTS: European public assessment report (EPAR) – Xigris®. London: Committee for Proprietary Medicinal Products, EMEA (2002).
   Google Scholar
• MACIAS W, DHAINAUT JF, YAN SC et al.: Pharmacokinetic-pharmacodynamic analysis of drotrecogin alfa (activated) in patients with severe sepsis. Clin. Pharmacol. Ther. (2002) 72(4):391-402.
   PubMed Web of Science ®Google Scholar
• NO AUTHORS LISTED: Xigris®: Summary of product characteristics. Eli Lilly Nederland BV, Grootslag 1-5, 3991 RA, Houten, The Netherlands. July 2005.
   Google Scholar
• BERNARD GR, ELY EW, WRIGHT TJ et al.: Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis. Crit. Care Med. (2001) 29(11):2051-2059.
   PubMed Web of Science ®Google Scholar
• LEVY H, SMALL D, HEISELMAN DE et al.: Obesity does not alter the pharmacokinetics of drotrecogin alfa (activated) in severe sepsis. Ann. Pharmacother. (2005) 39:262-267.
   PubMed Web of Science ®Google Scholar
• BARTON P, KALIL AC, NADEL S et al.: Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis. Pediatrics (2004) 113(1):7-17.
   PubMed Web of Science ®Google Scholar
• VAN DER POLL T, VAN DEVENTER SJ: Cytokines and anticytokines in the pathogenesis of sepsis. Infect. Dis. Clin. North Am. (1999) 13(2):413-426.
   PubMed Web of Science ®Google Scholar
• ROSENBERG RD, AIRD WC: Vascular-bed-specific hemostasis and hypercoagulable states. N. Engl. J. Med. (1999) 340(20):1555-1564.
   PubMed Web of Science ®Google Scholar
• MACKMAN N: Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler. Thromb. Vasc. Biol. (2004) 24(6):1015-1022.
   PubMed Web of Science ®Google Scholar
• DRAKE TA, MORRISSEY JH, EDGINGTON TS: Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am. J. Pathol. (1989) 134(5):1087-1097.
   PubMed Web of Science ®Google Scholar
• DRAKE TA, RUF W, MORRISSEY JH, EDGINGTON TS: Functional tissue factor is entirely cell surface expressed on lipopolysaccharide-stimulated human blood monocytes and a constitutively tissue factor-producing neoplastic cell line. J. Cell Biol. (1989) 109(1):389-395.
   PubMed Web of Science ®Google Scholar
• ANRATHER D, MILLAN MT, PALMETSHOFER A et al.: Thrombin activates nuclear factor-kappaB and potentiates endothelial cell activation by TNF. J. Immunol. (1997) 159(11):5620-5628.
   PubMed Web of Science ®Google Scholar
• ANDRE P, PRASAD KS, DENIS CV et al.: CD40L stabilizes arterial thrombi by a beta3 integrin-dependent mechanism. Nat. Med. (2002) 8(3):247-252.
   PubMed Web of Science ®Google Scholar
• NALDINI A, PUCCI A, CARNEY DH, FANETTI G, CARRARO F: Thrombin enhancement of interleukin-1 expression in mononuclear cells: involvement of proteinase-activated receptor-1. Cytokine (2002) 20(5):191-199.
   PubMed Web of Science ®Google Scholar
• YAN SB, DHAINAUT JF: Activated protein C versus protein C in severe sepsis. Crit. Care Med. (2001) 29(Suppl. 7):S69-S74.
   PubMed Web of Science ®Google Scholar
• ESMON CT: The protein C pathway. Chest (2003) 124(Suppl. 3):S26-S32.
   PubMed Web of Science ®Google Scholar
• ESMON CT: The anticoagulant and anti-inflammatory roles of the protein C anticoagulant pathway. J. Autoimmun. (2000) 15(2):113-116.
   PubMed Web of Science ®Google Scholar
• MANN KG, NESHEIM ME, CHURCH WR, HALEY P, KRISHNASWAMY S: Surface-dependent reactions of the vitamin K-dependent enzyme complexes. Blood (1990) 76(1):1-16.
   PubMed Web of Science ®Google Scholar
• NICOLAES GA, DAHLBACK B: Factor V and thrombotic disease: description of a janus-faced protein. Arterioscler. Thromb. Vasc. Biol. (2002) 22(4):530-538.
   PubMed Web of Science ®Google Scholar
• SAKATA Y, LOSKUTOFF DJ, GLADSON CL, HEKMAN CM, GRIFFIN JH: Mechanism of protein C-dependent clot lysis: role of plasminogen activator inhibitor. Blood (1986) 68(6):1218-1223.
   PubMed Web of Science ®Google Scholar
• BAJZAR L, NESHEIM ME, TRACY PB: The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent. Blood (1996) 88(6):2093-2100.
   PubMed Web of Science ®Google Scholar
• GREY ST, TSUCHIDA A, HAU H, ORTHNER CL, SALEM HH, HANCOCK WW: Selective inhibitory effects of the anticoagulant activated protein C on the responses of human mononuclear phagocytes to LPS, IFN-gamma, or phorbo ester. J. Immunol. (1994) 153(8):3664-3672.
   PubMed Web of Science ®Google Scholar
• SCHMIDT-SUPPRIAN M, MURPHY C, WHILE B et al.: Activated protein C inhibits tumour necrosis factor and macrophage migration inhibitory factor production in monocytes. Eur. Cytokine Netw. (2000) 11:407-413.
   PubMed Web of Science ®Google Scholar
• GRINNELL BW, HERMANN RB, YAN SB: Human protein C inhibits selectin-mediated cell adhesion: role of unique fucosylated oligosaccharide. Glycobiology (1994) 4(2):221-225.
   PubMed Web of Science ®Google Scholar
• CHRISTMAN JW, SADIKOT RT, BLACKWELL TS: The role of nuclear factor-kappa B in pulmonary diseases. Chest (2000) 117(5):1482-1487.
   PubMed Web of Science ®Google Scholar
• JOYCE DE, GRINNELL BW: Recombinant human activated protein C attenuates the inflammatory response in endothelium and monocytes by modulating nuclear factor-kappa B. Crit. Care Med. (2002) 30(Suppl. 5):S288-S293.
   PubMed Web of Science ®Google Scholar
• JOYCE DE, GELBERT L, CIACCIA A, DEHOFF B, GRINNELL BW: Gene expression profile of antithrombotic protein C defines new mechanisms modulating inflammation and apoptosis. J. Biol Chem. (2001) 276:11199-11203
   PubMed Web of Science ®Google Scholar
• LASZIK Z, MITRO A, TAYLOR FB JR, FERRELL G, ESMON CT: 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.
   PubMed Web of Science ®Google Scholar
• MOSNIER LO, GRIFFIN JH: Inhibition of staurosporine-induced apoptosis of endothelial cells by activated protein C requires protease-activated receptor-1 and endothelial cell protein C receptor. Biochem. J. (2003) 373(1):65-70.
   PubMed Web of Science ®Google Scholar
• ZENG W, MATTER WF, YAN SB, UM SL, VLAHOS CJ, LIU L: Effect of drotrecogin alfa (activated) on human endothelial cell permeability and Rho kinase signaling. Crit. Care Med. (2004) 32(Suppl. 5):S302-S308.
   PubMed Web of Science ®Google Scholar
• FEISTRITZER C, RIEWALD M: Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1- phosphate receptor-1 cross-activation. Blood (2005) 105(8):3178-3184.
   PubMed Web of Science ®Google Scholar
• CONWAY EM, VAN DE WOUWER M, POLLEFEYT S et al.: The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways. J. Exp. Med. (2002) 196(5):565-577.
   PubMed Web of Science ®Google Scholar
• TAYLOR FB JR, STEARNS-KUROSAWA DJ, KUROSAWA S et al.: The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. Blood (2000) 95(5):1680-1686.
   PubMed Web of Science ®Google Scholar
• DERHASCHNIG U, REITER R, KNÖBL P, BAUMGARTNER M, KEEN P, JILMA B: Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) has minimal effect on markers of coagulation, fibrinolysis, and inflammation in acute human endotoxemia. Blood (2003) 102(6):2093-2098.
   PubMed Web of Science ®Google Scholar
• KALIL AC, COYLE SM, UM JY et al.: Effects of drotrecogin alfa (activated) in human endotoxemia. Shock (2004) 21(3):222-229.
   PubMed Web of Science ®Google Scholar
• LATERRE PF, LEVY H, CLERMONT G et al.: Hospital mortality and resource use in subgroups of the recombinant human activated protein C worldwide evaluation in severe sepsis (PROWESS) trial. Crit. Care Med. (2004) 32(11):2207-2218.
   PubMed Web of Science ®Google Scholar
• ANGUS DC, LATERRE PF, HELTERBRAND J et al.: The effect of drotrecogin alfa (activated) on long term survival after severe sepsis. Crit. Care Med. (2004) 32(11):2199-2206.
   PubMed Web of Science ®Google Scholar
• OPAL SM, GARBER GE, LAROSA SP et al.: Systemic host responses in severe sepsis analysed by causative microorganism and treatment effects of drotrecogin alfa (activated). Clin. Infect. Dis. (2003) 37:50-58.
   PubMed Web of Science ®Google Scholar
• DHAINAUT JF, LATERRE PF, LAROSA SP et al.: The clinical evaluation committee in a large mutlicenter Phase III trial of drotrecogin alfa (activated) in patients with severe sepsis (PROWESS): role, methodology, and results. Crit. Care Med. (2003) 31:2291-2301.
   PubMed Web of Science ®Google Scholar
• ELY EW, LATERRE PF, ANGUS DC et al.: Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsis. Crit. Care Med. (2003) 31:12-19.
   PubMed Web of Science ®Google Scholar
• WHEELER AP, STEINGRUB J, LINDE-ZWIRBLE W et al.: Prompt administration of drotrecogin alfa (activated) is associated with improved survival. Crit. Care Med. (2003) 31(Suppl. 12):A120.
   PubMed Web of Science ®Google Scholar
• SCHMIDT G, BATES B, MCCOLLAM JS, STEINGRUB J: Clinical use of drotrecogin alfa (activated): Patients treated in MERCURY differ from those in PROWESS. Society of Critical Care Medicine 33rd Annual Congress. Orlando, Florida (2004). Crit. Care Med. (2003) 31(Suppl. 12):A116.
   Google Scholar
• VINCENT JL, BERNARD GR, BEALE R et al.: Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: Further evidence for survival and safety and implications for early treatment. Crit. Care Med. (2005) 33(10):2266-2277.
   PubMed Web of Science ®Google Scholar
• WHEELER AP, DOIG C, WRIGHT T, WONG K, VINCENT JL, BERNARD G: Baseline characteristics and survival of adult severe sepsis patients treated with drotrecogin alfa (activated) in a global, single-arm, open-label trial (ENHANCE). Abstract. Chest (2003) 124:S91-S92.
   Google Scholar
• VINCENT JL, LEVY MM, MACAIS WL, TRZASKOMA BL: Early intervention with drotrecogin alfa (activated) improves survival benefit. Crit. Care Med. (2003) 31(Suppl. 12):A123.
   Google Scholar
• BERNARD GR, MARGOLIS BD, SHANIES HM et al.: Extended evaluation of recombinant human activated protein C United States trial (ENHANCE US): a single-arm, Phase IIIB, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest (2004) 125:2206-2216.
   PubMed Web of Science ®Google Scholar
• LATERRE PF, BERNARD GR, TRZASKOMA B, SASHEGYI A: INDEPTH – an integrated database of severe sepsis patients. Society of Critical Care Medicine 33rd Annual Congress. Orlando, Florida (2004). Crit. Care Med. (2003) 31(Suppl. 12):A1-A150.
   Web of Science ®Google Scholar
• NAST-KOLB D, WAYDHAS C, GIPPNER-STEPPERT C et al.: Indicators of the posttraumatic inflammatory response correlate with organ failure in patients with multiple injuries. J. Trauma (1997) 42(3):446-454
   PubMed Web of Science ®Google Scholar
• VINCENT JL, ANGUS DC, ARTIGAS A et al.: Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial. Crit. Care Med. (2003) 31:834-840.
   PubMed Web of Science ®Google Scholar
• DHAINAUT JF, LATERRE PF, JANES JM et al.: Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple organ dysfunction: data from the PROWESS trial. Intensive Care Med. (2003) 29:894-903.
   PubMed Web of Science ®Google Scholar
• LEVI M, TEN CATE H: Disseminated intravascular coagulation. N. Engl. J. Med. (1999) 341(8):586-592.
   PubMed Web of Science ®Google Scholar
• BROHI K, SINGH J, HERON M, COATS T: Acute traumatic coagulopathy. J. Trauma (2003) 54:1127-1130.
   PubMed Web of Science ®Google Scholar
• GANDO S: Disseminated intravascular coagulation in trauma patients. Semin. Thromb. Hemost. (2001) 27(6):585-592.
   PubMed Web of Science ®Google Scholar
• DHAINAUT JF, YAN SB, JOYCE DE et al.: Treatment of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J. Thromb. Haemost. (2004) 2:1924-1933.
   PubMed Web of Science ®Google Scholar
• AOKI N, MATSUDA T, SAITO H et al.: A comparative double-blind randomized trial of activated protein C and unfractionated heparin in the treatment of disseminated intravascular coagulation. Int. J. Hematol. (2002) 75:540-547.
   PubMed Web of Science ®Google Scholar
• ELY EW, ANGUS DC, WILLIAMS MD, BATES B, QUALY R, BERNARD G: Drotrecogin alfa (activated) treatment of older patients with severe sepsis. Clin. Infect. Dis. (2003) 37:178-195.
   Google Scholar
• GOMBERG BF, GRUEN GS, SMITH WR, SPOTT M: Outcomes in acute orthopaedic trauma: a review of 130,506 patients by age. Injury (1999) 30:431-437.
   PubMed Web of Science ®Google Scholar
• DREYFUS M, MASTERSON M, DAVID M et al.: Replacement therapy with a monoclonal antibody purified protein C concentrate in newborns with severe congenital protein C deficiency. Semin. Thromb. Hemost. (1995) 21(4):371-381.
   PubMed Web of Science ®Google Scholar
• WHITE B, LIVINGSTONE W, MURPHY C, HODGSON A, RAFFERTY M, SMITH OP: An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia. Blood (2000) 96(12):3719-3724.
   PubMed Web of Science ®Google Scholar
• FROMMHOLD D, BIRLE A, LINDERKAMP O, ZILOW E, POSCHL J: Drotrecogin alfa (activated) in neonatal septic shock. Scand J. Infect. Dis. (2005) 37(4):306-308.
   PubMed Web of Science ®Google Scholar
• FAUST SN, LEVIN M, HARRISON OB et al.: Dysfunction of Endothelial protein C activation in severe meningococcal sepsis. N. Engl. J. Med. (2001) 345(6):408-416.
   PubMed Web of Science ®Google Scholar
• BARIE PS, WILLIAMS MD, MCCOLLAM JS et al.: Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with severe sepsis. Am. J. Surg. (2004) 188(3):212-220.
   PubMed Web of Science ®Google Scholar
• MIKASZEWSKA-SOKOLEWICZ M, NIEREBINSKA M, MAYZNER-ZAWADZKA E: Use of drotrecogin alfa in two patients with severe sepsis. Med. Sci. Monit. (2003) 9(8):CS80-CS87.
   PubMedGoogle Scholar
• MACHALA W, WACHOWICZ N, KOMOROWSKA A, GASZYNSKI W: The use of drotrecogin alfa (activated) in severe sepsis during acute pancreatitis – two case studies. Med. Sci. Monit. (2004) 10(7):CS31-CS36.
   PubMed Web of Science ®Google Scholar
• BIERNACKA J, WOSKO J, DABROWSKI W, NESTOROWICZ A: Use of drotrecogin alfa-recombinant activated human protein C in treatment of septic shock in the course of therapy for nephrolithiasis. Med. Sci. Monit. (2003) 9(5):CS25-CS28.
   PubMedGoogle Scholar
• BRUECKMANN M, WIZENMANN J, HOFFMANN U, SEEGER M, BEWIG B: Clinical and laboratory effects of recombinant human activated protein C in the treatment of a patient with sepsis-induced multiple organ failure. Thromb. Res. (2003) 15(109):259-263.
   Google Scholar
• BERNARD GR, MACIAS WL, JOYCE DE, WILLIAMS MD, BAILEY J, VINCENT JL: Safety assessment of drotrecogin alfa (activated) in the treatment of adult patients with severe sepsis. Crit. Care (2003) 7(2):155-163.
   PubMed Web of Science ®Google Scholar
• SAKAMOTO T, OGAWA H, TAKAZOE K et al.: Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase: comparison with unfractionated heparin. J. Am. Coll. Cardiol. (2003) 42:1389-1394.
   PubMed Web of Science ®Google Scholar
• VON DADELSZEN P, MAGEE LA, LEE SK et al.: Activated protein C in normal human pregnancy and pregnancies complicated by severe preeclampsia: A therapeutic opportunity? Crit. Care Med. (2002) 30:1883-1892.
   PubMed Web of Science ®Google Scholar
• ELI LILLY: Xigris NICE submission: drotrecogin alfa (activated) for severe sepsis. Basingstoke: Eli Lilly (2003).
   Google Scholar
• DHAINAUT JF, LATERRE PF, NELSON DR, HUANG C, JANES J: Safety profile of drotrecogin alfa (activated) in severe sepsis patients from the INDEPTH integrated database. Crit. Care Med. (2004) 32(Suppl. 12):A174.
   Google Scholar
• STEINGRUB J, SANCHEZ P, ZECKEL M, BATES B, QUALY R: Safety of drotrecogin alfa (activated): Results of MERCURY, a retrospective multi-center observational study. Society of Critical Care Medicine 33rd Annual Congress. Orlando, Florida (2004). Crit. Care Med. (2003) 31(Suppl. 12):A1-A150.
   Web of Science ®Google Scholar
• LATERRE PF, HEISELMAN DO: Management of patients with severe sepsis, treated by drotrecogin alfa (activated). Am. J. Surg. (2002) 184(Suppl. 6A):S39-S46.
   PubMed Web of Science ®Google Scholar
• XIGRIS MONOGRAPH. Eli Lilly and Company Ltd Basingstoke, UK. XIG 136. October (2002).
   Google Scholar
• BRITISH NATIONAL FORMULARY: London: British Medical Association and the Royal Pharmaceutical Society of Great Britain (2002).
   Google Scholar
• DAVIES A, RIDLEY S, HUTTON J, CHINN C, BARBER B, ANGUS DC: Cost effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in the United Kingdom. Anaesthesia (2005) 60:155-162.
   PubMed Web of Science ®Google Scholar
• MANNS BJ, LEE H, DOIG CJ, JOHNSON D, DONALDSON C: An economic evaluation of activated protein C treatment for severe sepsis. N. Engl. J. Med. (2002) 347:993-1000.
   PubMed Web of Science ®Google Scholar
• ANGUS DC, LINDE-ZWIRBLE WT, CLERMONT G et al.: Cost effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis. Crit. Care Med. (2003) 31(1):1-11.
   PubMed Web of Science ®Google Scholar
• ALTMAN DG, SCHULZ KF, MOHER D et al.: The revised CONSORT statement for reporting randomised trials: explanation and elaboration. Ann. Intern. Med. (2001) 134:663-694.
   PubMed Web of Science ®Google Scholar