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Human protein C concentrate in pediatric septic patients

  • GIOVANNI LANDONIĆ1
  • GIACOMO MONTI1
  • ALBERTO FACCHINI1
  • FRANCESCO CAMA1
  • ELENA BIGNAMI1
  • LUCA CABRINI1
  • FEDERICO PAPPALARDO1
  • ALBERTO ZANGRILLO1

1,Department of Anesthesia and Intensive Care Università Vita-Salute San Raffaele Milano

DOI: 10.22514/SV51.042010.2 Vol.5,Issue 1,April 2010 pp.13-19

Published: 27 April 2010

*Corresponding Author(s): GIOVANNI LANDONIĆ E-mail: landoni.giovanni@hsr.it

Abstract

Severe sepsis and septic shock are leading causes of morbidity and mortality in the pediatric population. Unlike what is suggested for the adult population, recombinant human activated protein C (rhAPC) is contraindicated in children. Long before rhAPC was considered for use in pediatric patients, case reports appeared on the safe administration of protein C zymogen. Therefore, we conducted a systemic review of currently available data on protein C zymogen (PC) use among children affected by severe sepsis or septic shock. 

A total number of 13 case series or case reports and a dose-finding study were found on the use of PC in the pediatric intensive care unit, reporting on 118 treated children, with an overall survival of 84%. There was no bleeding complication, the only reported complication being a single mild allergic reaction.

These studies show that PC is safe, not associated with bleeding and possibly useful for improving coagulation abnormali-ties of sepsis.

Keywords

sepsis, pediatric, protein C, drug therapy, review

Cite and Share

GIOVANNI LANDONIĆ,GIACOMO MONTI,ALBERTO FACCHINI,FRANCESCO CAMA,ELENA BIGNAMI,LUCA CABRINI,FEDERICO PAPPALARDO,ALBERTO ZANGRILLO. Human protein C concentrate in pediatric septic patients. Signa Vitae. 2010. 5(1);13-19.

References

1. Watson RS, Carcillo JA. Scope and epidemiology of pediatric sepsis. Pediatr Crit Care Med 2005;6:3-5.

2. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 2003; 167:695-701.

3. Wolfler A, Silvani P, Musicco M, Antonelli M, Salvo I. (Italian Pediatric Sepsis Study (SISPe) group) Incidence of and mortality due to sepsis, severe sepsis and septic shock in Italian Pediatric Intensive Care Units: a prospective national survey . Intensive Care Med 2008;34:1690-7.

4. Dellinger R, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. For the International Surviving Sepsis Campaign Guidelines Committee Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008;36:296-327.

5. Finfer S, Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, et al. Design, conduct, analysis and reporting of a multi-national placebo-controlled trial of activated protein C for persistent septic shock. Intensive Care Med 2008;34:1935-47.

6. Nadel S, Goldstein B, Williams MD, Dalton H, Peters M, Macias WL, et al. REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) study group. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 2007;369:836–43.

7. Gerson WT, Dickerman JD, Bovill EG, Golden E. Severe acquired protein C deficiency in purpura fulminans associated with disseminated intravascular coagulation: treatment with protein C concentrate. Pediatrics 1993;91:418-22.

8. Rivard GE, David M, Farrell C, Schwarz HP. Treatment of purpura fulminans in meningococcemia with protein C concentrate. J Pediatr 1995;126:646-52.

9. Smith OP, White B, Vaughan D, Rafferty M, Claffey L, Lyons B, et al. Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans. Lancet 1997;29:1590-3.

10. Ettingshausen CE, Veldmann A, Beeg T, Schneider W, Jäger G, Kreuz W. Replacement therapy with protein C concentrate in infants and adolescents with meningococcal sepsis and purpura fulminans. Semin Thromb Hemost 1999;25:537-41.

11. Clarke RC, Johnston JR, Mayne EE. Meningococcal septicaemia: treatment with protein C concentrate. Intensive Care Med 2000;26:471-3.

12. Leclerc F, Cremer R, Leteurtre S, Martinot A, Fourier C. Protein C concentrate and recombinant tissue plasminogen activator in meningo-coccal septic shock. Crit Care Med 2000;28:1694-7.

13. 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;96:3719-24.

14. Fourrier F, Leclerc F, Aidan K, Sadik A, Jourdain M, Tournoys A, et al. Combined antithrombin and protein C supplementation in menin-gococcal purpura fulminans: a pharmacokinetic study. Intensive Care Med 2003;29:1081-7.

15. Pettenazzo A, Malusa T. Use of protein C concentrate in critical conditions: clinical experience in pediatric patients with sepsis. Minerva Anestesiol 2004;70:357-63.

16. Silvani P, Camporesi A, Licari E, Wolfler A. Use of protein C concentrate in pediatric patients with sepsis. Minerva Anestesiol 2005;71:373-8.

17. De Carolis MP, Polimeni V, Papacci P, Lacerenza S, Romagnoli C. Severe sepsis in a premature neonate: protein C replacement therapy. Turk J Pediatr 2008;50:405-8.

18. Makris PE, Girtovitis F, Papadopoulos A, Tamioulaki A. Treatment of DIC: the role of PC. J Thromb Haemost 2003;1S1:P0600.

19. Schellongowski P, Bauer E, Holzinger U, Staudinger T, Frass M, Laczika K, et al. Treatment of adult patients with sepsis-induced coagu-lopathy and purpura fulminans using a plasma-derived protein C concentrate (Ceprotin®). Vox Sanguinis 2006;90:294-301.

20. de Kleijn ED, de Groot R, Hack CE, Mulder PG, Engl W, Moritz B, Joosten KF, 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;31:1839-47.

21. Evans SF, Johnson P, Garewal DS, Khan ZP. Glasgow meningococcal septicaemia prognostic score. Crit Care Med 1992;20:439.

22. Landoni G, Crivellari M, Monti G, Gerli C. Human protein C concentrates in adult septic patients. Signa Vitae 2008;3:12-16,301.

23. Crivellari M, Della Valle P, Landoni G, Pappalardo F, Gerli C, Bignami E, et al. Human protein C zymogen concentrate in patients with severe sepsis and multiple organ failure after adult cardiac surgery. Intensive Care Med 2009 Aug 1. [Epub ahead of print]

24. Russell JA. Management of sepsis. N Engl J Med 2006;355:1699-713.

25. Cohen J. The immunopathogenesis of sepsis. Nature 2002;420:885-91.

26. Esmon CT. Crosstalk between inflammation and thrombosis. Maturitas 2004; 47:305–14.

27. Bae JS, Yang L, Rezaie AR. Receptors of the protein C activation and activated protein C signaling pathways are colocalized in lipid rafts of endothelial cells. Proc Natl Acad Sci U S A 2007;104:2867-72.

28. Polli F, Savioli M, Cugno M, Taccone P, Bellani G, Spanu P, et al. Effects of recombinant human activated protein C on the fibrinolytic system of patients undergoing conventional or tight glycemic control. Minerva Anestesiol 2009;75:417-26.

29. Schultz MJ, Levi M. Recombinant human activated protein C and strict glycemic control in sepsis: mutually exclusive strategies? Minerva Anestesiol 2009;75:415-6.

30. Yan SB, Dhainaut JF. Activated protein C versus protein C in severe sepsis. Crit Care Med 2001;29:S69-74.

31. Esmon CT. Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflammation. Crit Care Med 2001;29:S48-51.

32. Bae JS, Rezaie AR. Protease activated receptor 1 (PAR-1) activation by thrombin is protective in human pulmonary artery endothelial cells if endothelial protein C receptor is occupied by its natural ligand. Thromb Haemost 2008;100:101-9.

33. Weiler H, Ruf W. Activated protein C in sepsis: the promise of nonanticoagulant activated protein C. Curr Opin Hematol 2008;15:487-93.

34. Kerschen EJ, Fernandez JA, Cooley BC, Yang XV, Sood R, Mosnier LO, et al. Endotoxemia and sepsis mortality reduction by non-antico-agulant activated protein C. J Exp Med 2007;204:2439-48.

35. Andrew M, Paes B, Johnston M. Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hematol Oncol 1990;12:95-104.

36. Fisher CJ Jr, Yan SB. Protein C levels as a prognostic indicator of outcome in sepsis and related diseases. Crit Care Med 2000;28:S49-56.

37. Faust SN, Levin M, Harrison OB, Goldin RD, Lockhart MS, Kondaveeti S, et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med 2001;345:408-16.

38. Liaw PC, Esmon CT, Kahnamoui K, Schmidt S, Kahnamoui S, Ferrell G, et al. Patients with severe sepsis vary markedly in their ability to generate activated protein C. Blood 2004;104:3958-64.

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