Article Data

  • Views 1722
  • Dowloads 128

Review

Open Access

Administration of protein C concentrates in patients without congenital deficit: a systematic review of the literature

  • SIMONA SILVETTI1
  • MARTINA CRIVELLARI1
  • MARTA MUCCHETTI1
  • DAIANA TADDEO1
  • ANNALISA FRANCO1
  • GIOVANNI LANDONI1
  • ALBERTO ZANGRILLO1

1,Department of Anesthesia and Intensive Care Istituto Scientifico San Raffaele

DOI: 10.22514/SV82.102013.2 Vol.8,Issue 2,October 2013 pp.15-19

Published: 17 October 2013

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

Abstract

Endogenous protein C levels are frequently decreased in septic patients, probably due to increased conversion to activated protein C. Protein C levels inversely correlate with morbidity and mortality of septic patients regardless of age, infecting microorganisms, presence of shock, disseminated intravascular coagulation, degree of hypercoagulation, or severity of illness. Taken together, these considerations suggest a strong correlation between protein C pathways and survival from severe sepsis/septic shock, and reinforce the rationale for the attempts to normalize plasma activity of protein C to improve survival, hamper coagulopathy, and modulate inflammation. We therefore conducted a systematic review of all manuscripts describing protein C concentrates administration in adult and pediatric populations. We identified 28 studies, for a total of 340 patients, 70 of whom died (20.6%). Septic patients were the most represented in this review of case reports and case series. In the majority of these patients sepsis was associated with meningitis, purpura fulminans or disseminated intravas-cular coagulation. No bleeding complications related to the study drug were reported and most studies underlined norma-lization of inflammatory markers and of coagulation abnormalities. We conclude that protein C concentrate is an attractive option in septic patients (especially those with meningitis, purpura fulminans, or disseminated intravascular coagulation) and that its cost-benefit ratio must be studied with a large multicenter randomized control trial, possibly including also high risk patients with septic shock and multiple organ failure.

Keywords

protein C zymogen, blee-ding, amputations, intensive care, critical care

Cite and Share

SIMONA SILVETTI,MARTINA CRIVELLARI,MARTA MUCCHETTI,DAIANA TADDEO,ANNALISA FRANCO,GIOVANNI LANDONI,ALBERTO ZANGRILLO. Administration of protein C concentrates in patients without congenital deficit: a systematic review of the literature. Signa Vitae. 2013. 8(2);15-19.

References

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

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

3. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker M. Surviving sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2008;36:296-327.

4. Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, et al. PROWESS-SHOCK Study Group. Drotrecogin Alfa (Activated) in Adults with Septic Shock. N Engl J Med 2012;366:2055-64.

5. Dreyfus M, Magny JF, Bridey F, Schwarz HP, Planché C, Dehan M, et al. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med 1991;325:1565-8.

6. Crivellari M, Della Valle P, Landoni G, Pappalardo F, Gerli C, Bignami E, et al. Human protein C zymogen concentrates with severe sepsis and multiple organ failure after adult cardiac surgery. Intensive Care Med 2009;35:1959–63.

7. Baratto F, Michielan F, Meroni M, Dal Palù A, Boscolo A, Ori C. Protein C concentrate to restore physiological values in adult septic patients. Intensive Care Med 2008;34:1707-12.

8. Landoni G, Crivellari M, Monti G, Gerli C, Silvani P, Zangrillo A. Human protein C concentrates in adult septic patients. Signa vitae 2008;3:13-7.

9. XXTuttolomondo A, Pinto A, Di Raimondo D, Fernandez P, Licata G. Plasma derived protein C in severe sepsis: report of two cases. Intern Emerg Med 2008;3:179- 82.

10. Vaccarella G, Pelella R. Replacement treatment with protein C in an 18-year-old man with meningococcal sepsis and purpura fulminans. Minerva Anestesiol 2003;69:691- 3.

11. Rintala E, Kauppila M, Seppälä OP, Voipio-Pulkki LM, Pettilä V, Rasi V, et al. Protein C substitution in sepsis-associated purpura fulminans. Critical Care Med 200;28:2373-78.

12. 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 Sang 2006;90:294-301.

13. Makris PE, Girtovitis F, Papadopoulos A, Tamioulaki A, Kosmidou M, Pithara E. Treatment of DIC: the role of PC. J Thromb Haemost 2003;1(Suppl 1):abstract P0600.

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

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

16. 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.

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

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

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

20. De Kleijn ED, De Groot R, Hack CE, Mulder PG, Engl W, Moritz B, 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. 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.

22. 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.

23. 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.

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

25. 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.

26. Malato A, Saccullo G, Coco LL, Caracciolo C, Raso S, Santoro M, et al. Safety of plasma-derived protein C for treating disseminated intravascular coagulation in adult patients with active cancer. Am J Hematol 2011 Oct 31. doi: 10.1002/ajh.22238.

27. Betrosian AP, Memos N, Theoddossiades G, Douzinas EE. Protein C concentrate in adult septic patients. Intensive Care Med 2008;34:1932.

28. Morelli A, Donati A, Di Russo A, D’Ippolito F, Raffone C, D’Egidio A, et al. Human protein C concentrate to restore physiological values in adult septic shock patients: effects on microcirculation. Crit Care 2012;16 (Suppl 1):P201 doi: 10.1186/cc10808.

29. Veldman A, Fischer D, Wong FY, Kreuz W, Sasse M, Eberspächer B, et al. Human protein C concentrate in the treatment of purpura fulmi-nans: a retrospective analysis of safety and outcome in 94 pediatric patients. Crit Care 2010;14: R156.

30. Kreuz W, Veldman A, Escuriola-Ettingshausen C, Schneider W, Beeg T. Protein-C concentrate for meningococcal purpura fulminans. Lancet 1998;351:986-7.

31. Lignell A, Siegbahn A, Stridsberg M, Pauksen K, Gedeborg R, Sjolin J. Low utilisation of unactivated protein C in a patient with meningo-coccal septic shock and disseminated intravascular coagulation. Acta Anaesthesiol Scand 2003;47:897-900.

32. Ruffini E, Osimani P, Jorini M, Cordiali R, Pagni R, De Benedictis FM. Treatment of purpura fulminans with protein C concentrate: A further scientific evidence. Italian Journal of Pediatrics 2004; 30:169-73.

33. Behrendt J, Karpe J, Sadownik B, Wasek M, Godula-Stuglik U. Substitution of human protein C concentrates in the treatment of late-onset sepsis in preterm neonates (preliminary report). Pediatria polska 2005;124-28.

34. Rintala E, Kauppila M, Seppälä OP, Voipio-Pulkki LM, Pettilä V, Rasi V, et al. Protein C substitution in sepsis-associated purpura fulminans. Crit Care Med 1998;28:2373-8.

35. Baratto F, Michielan F, Gagliardi G, Di Gregorio G, Pasqualetto A, Meroni M, et al. Use of protein C concentrate in adult patients with severe sepsis and septic shock. Minerva Anestesiol 2004;70:351-6.

36. Fischer D, Schloesser RL, Nold-Petry CA, Nold MF, Veldman A. Protein C concentrate in preterm neonates with sepsis. Acta Pædiatrica ISSN 0803–5253

37. 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.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.

Index Copernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.

Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.

Scopus: CiteScore 1.0 (2022) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.

Submission Turnaround Time

Conferences

Top