Circulating nucleosomes and severity of illness in children suffering from meningococcal sepsis treated with protein C

Critical Care Medicine

Volumn 40, Issue 12, 2012, Pages 3224-3229

  Zeerleder, Sacha ^a,b   Stephan, Femke ^a   Emonts, Marieke ^c,d   De Kleijn, Ester D ^c   Esmon, Charles T ^e   Varadi, Katalin ^f   Hack, Cornelis Erik ^g   Hazelzet, Jan A ^c  

^a CENTRAL LABORATORY   (Netherlands)

^b ACADEMIC MEDICAL CENTER   (Netherlands)

^c SOPHIA CHILDREN S HOSPITAL   (Netherlands)

^d ERASMUS MEDICAL CENTER   (Netherlands)

^e OKLAHOMA MEDICAL RESEARCH FOUNDATION   (United States)

^f BAXTER BIOSCIENCE   (Austria)

^g UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

activated protein C; histones; meningococcal sepsis; nucleosomes; protein C

Indexed keywords

PLACEBO; PROTEIN C;

ADOLESCENT; ADULT; ANTIMICROBIAL THERAPY; ARTICLE; CHILD; CHILDHOOD MORTALITY; CLINICAL ARTICLE; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG EFFECT; HUMAN; INFANT; INFLAMMATION; INTENSIVE CARE UNIT; MENINGOCOCCEMIA; NUCLEOSOME; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RETROSPECTIVE STUDY; SCHOOL CHILD;

ADOLESCENT; BACTEREMIA; CHILD; CHILD, PRESCHOOL; DOUBLE-BLIND METHOD; FIBRINOLYTIC AGENTS; HUMANS; INFANT; INTENSIVE CARE UNITS, PEDIATRIC; MENINGOCOCCAL INFECTIONS; NETHERLANDS; NUCLEOSOMES; PROTEIN C; RETROSPECTIVE STUDIES; SEPSIS; SEVERITY OF ILLNESS INDEX;

EID: 84870245911     PISSN: 00903493     EISSN: 15300293     Source Type: Journal    
DOI: 10.1097/CCM.0b013e318265695f     Document Type: Article

References (42)

1. Pathan N, Faust SN, Levin M: Pathophysiology of meningococcal meningitis and septicaemia. Arch Dis Child 2003; 88:601-607
2. Zeerleder S, Hack CE, Wuillemin WA: Disseminated intravascular coagulation in sepsis. Chest 2005; 128:2864-2875
3. Esmon CT: The roles of protein C and thrombomodulin in the regulation of blood coagulation. J Biol Chem 1989; 264: 4743-4746
4. Cheng T, Liu D, Griffin JH, et al: Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective. Nat Med 2003; 9:338-342
5. Grey ST, Tsuchida A, Hau H, et al: Selective inhibitory effects of the anticoagulant activated protein C on the responses of human mononuclear phagocytes to LPS, IFN-gamma, or phorbol ester. J Immunol 1994; 153:3664-3672
6. 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(Pt 1):65-70
7. Mosnier LO, Zlokovic BV, Griffin JH: The cytoprotective protein C pathway. Blood 2007; 109:3161-3172
8. de Kleijn ED, de Groot R, Hack CE, et al: Activation of protein C following infusion of protein C concentrate in children with severe meningococcal sepsis and purpura fulminans: A randomized, double-blinded, placebo-controlled, dose-finding study. Crit Care Med 2003; 31:1839-1847
9. Ettingshausen CE, Veldmann A, Beeg T, et al: Replacement therapy with protein C concentrate in infants and adolescents with meningococcal sepsis and purpura fulminans. Semin Thromb Hemost 1999; 25:537-541
10. Gerson WT, Dickerman JD, Bovill EG, et al: Severe acquired protein C deficiency in purpura fulminans associated with disseminated intravascular coagulation: Treatment with protein C concentrate. Pediatrics 1993; 91:418-422
11. Hasin T, Leibowitz D, Rot D, et al: Early treatment with activated protein C for meningococcal septic shock: Case report and literature review. Intensive Care Med 2005; 31:1002-1003
12. Kreuz W, Veldman A, Escuriola-Ettingshausen C, et al: Protein-C concentrate for meningococcal purpura fulminans. Lancet 1998; 351:986-987; author reply 988
13. Rintala E, Kauppila M, Seppälä OP, et al: Protein C substitution in sepsis-associated purpura fulminans. Crit Care Med 2000; 28:2373-2378
14. White B, Livingstone W, Murphy C, et al: An open-label study of the role of adjuvant hemostatic support with protein C replacement therapy in purpura fulminans-associated meningococcemia. Blood 2000; 96:3719-3724
15. Vincent JL, Nadel S, Kutsogiannis DJ, et al: Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: A retrospective analysis of patients enrolled in recent clinical studies. Crit Care 2005; 9:R331-R343
16. Veldman A, Fischer D, Wong FY, et al: Human protein C concentrate in the treatment of purpura fulminans: A retrospective analysis of safety and outcome in 94 pediatric patients. Crit Care 2010; 14:R156
17. Hotchkiss RS, Nicholson DW: Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol 2006; 6:813-822
18. Hotchkiss RS, Tinsley KW, Swanson PE, et al: Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans. J Immunol 2001; 166:6952-6963
19. Zeerleder S, Zwart B, Wuillemin WA, et al: Elevated nucleosome levels in systemic inflammation and sepsis. Crit Care Med 2003; 31:1947-1951
20. Massberg S, Grahl L, von Bruehl ML, et al: Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 2010; 16:887-896
21. Xu J, Zhang X, Pelayo R, et al: Extracellular histones are major mediators of death in sepsis. Nat Med 2009; 15:1318-1321
22. Holdenrieder S, Stieber P, Bodenmüller H, et al: Nucleosomes in serum as a marker for cell death. Clin Chem Lab Med 2001; 39:596-605
23. Earnshaw WC: Nuclear changes in apoptosis. Curr Opin Cell Biol 1995; 7:337-343
24. Amoura Z, Piette JC, Bach JF, et al: The key role of nucleosomes in lupus. Arthritis Rheum 1999; 42:833-843
25. Zeerleder S, Zwart B, te Velthuis H, et al: A plasma nucleosome releasing factor (NRF) with serine protease activity is instrumental in removal of nucleosomes from secondary necrotic cells. FEBS Lett 2007; 581:5382-5388
26. Vincent JL, de Mendonça A, Cantraine F, et al: Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: Results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med 1998; 26:1793-1800
27. Pollack MM, Ruttimann UE, Getson PR: Pediatric risk of mortality (PRISM) score. Crit Care Med 1988; 16:1110-1116
28. Leclerc F, Hazelzet J, Jude B, et al: Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Intensive Care Med 1992; 18:202-205
29. Kornelisse RF, Hazelzet JA, Hop WC, et al: Meningococcal septic shock in children: Clinical and laboratory features, outcome, and development of a prognostic score. Clin Infect Dis 1997; 25:640-646
30. Gruber A, Griffin JH: Direct detection of activated protein C in blood from human subjects. Blood 1992; 79:2340-2348
31. de Boer JP, Abbink JJ, Brouwer MC, et al: PAI-1 synthesis in the human hepatoma cell line HepG2 is increased by cytokines-Evidence that the liver contributes to acute phase behaviour of PAI-1. Thromb Haemost 1991; 65:181-185
32. Boermeester MA, van Leeuwen PA, Coyle SM, et al: Interleukin-1 blockade attenuates mediator release and dysregulation of the hemostatic mechanism during human sepsis. Arch Surg 1995; 130:739-748
33. Levi M, de Boer JP, Roem D, et al: Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative assessment of plasmin-alpha 2-antiplasmin complex with a novel monoclonal antibody based radioimmunoassay. Thromb Haemost 1992; 67:111-116
34. Kurosawa S, Stearns-Kurosawa DJ, Carson CW, et al: Plasma levels of endothelial cell protein C receptor are elevated in patients with sepsis and systemic lupus erythematosus: Lack of correlation with thrombomodulin suggests involvement of different pathological processes. Blood 1998; 91:725-727
35. Zeerleder S, Caliezi C, van Mierlo G, et al: Administration of C1 inhibitor reduces neutrophil activation in patients with sepsis. Clin Diagn Lab Immunol 2003; 10:529-535
36. van Nieuwenhuijze AE, van Lopik T, Smeenk RJ, et al: Time between onset of apoptosis and release of nucleosomes from apoptotic cells: Putative implications for systemic lupus erythematosus. Ann Rheum Dis 2003; 62:10-14
37. Zeerleder S, Zwart B, te Velthuis H, et al: Nucleosome-releasing factor: A new role for factor VII-activating protease (FSAP). FASEB J 2008; 22:4077-4084
38. Brinkmann V, Reichard U, Goosmann C, et al: Neutrophil extracellular traps kill bacteria. Science 2004; 303:1532-1535
39. 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
40. Liaw PC: Endogenous protein C activation in patients with severe sepsis. Crit Care Med 2004; 32(5 Suppl):S214-S218
41. Liaw PC, Esmon CT, Kahnamoui K, et al: Patients with severe sepsis vary markedly in their ability to generate activated protein C. Blood 2004; 104:3958-3964
42. de Fouw NJ, de Jong YF, Haverkate F, et al: Activated protein C increases fibrin clot lysis by neutralization of plasminogen activator inhibitor-No evidence for a cofactor role of protein S. Thromb Haemost 1988; 60:328-333