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First experiences with protein C concentrate in adult patients with severe sepsis and septic shock associated to low protein C levels: a dose-finding study


To describe the first experiences on the use of protein C concentrate (PC) in adult patients with severe sepsis and septic shock and clinical contraindications to activated protein C (APC). On the basis of the effectiveness demonstrated by the activated form in sepsis and of the encouraging results expressed in the literature of PC mainly about meningococcus fulminating infections, we carried out an observational study on PC with 28-day follow-up and a daily analysis of the hematochemical and clinical parameters. Particular attention was paid to the variations in the PC plasma levels, to the modifications of the coagulation system, to the SOFA score as well as to the safety under bleeding risk conditions. The study included 10 patients (seven females and three males) either with severe sepsis (four patients) or septic shock (six patients); one of them had DIC, with PC plasma levels less than 50%. APC could not be administered because of clinical reasons. Patients' mean age was 63.5 years (43–78), the average SAPS II was 51.8 (36–72), and the pathologies leading to sepsis were lung infections (three patients), peritonitis (five patients), and one patient with cutaneous and one patient with haematological origin. The average time elapsed between the onset of the organ failure and the beginning of treatment with PC was 27.7 hours (12–42).


Mortality on day 28 was 30% (three deaths), in all patients the PC plasma levels were brought again to the physiological values. The bolus-dose delivered was the following: UI of protein C = (100 - plasmatic basal level of PC) × body weight. It was followed by a continuos infusion of 3 IU/kg/hour for 72 hours. Among the parameters recorded during the PC infusion was observed in particular a significant decrease of PDFs, a general rise of the platelet count, and a reduction of the lactic acid levels. No adverse reaction or bleeding complication were seen, even if most of the patients' coagulation was altered or at risk due to neurological problems or repeated surgery.


In our small number of patients, protein C concentrate has proven to be safe and particularly useful in the control of the coagulopathy triggered and sustained by sepsis.


  1. 1.

    Pescatore SL: Clinical management of protein C deficiency. Expert Opin Pharmacother 2001, 2: 431-439.

    PubMed  CAS  Article  Google Scholar 

  2. 2.

    Fisher CJ Jr, Yan SB: Protein C levels as a prognostic indicator of outcome in sepsis and related diseases. Crit Care Med 2000,28(9 suppl):S49-S56. 10.1097/00003246-200009001-00011

    PubMed  Article  Google Scholar 

  3. 3.

    Clarke RCN, Johnston JR, Mayne EE: Meningococcal septicaemia: treatment with protein C concentrate. Intensive Care Med 2000, 26: 471-473. 10.1007/s001340051184

    PubMed  CAS  Article  Google Scholar 

  4. 4.

    De Kleijn ED, De Groot R, Hack CE, H Mulder PG, Engl W, Moritz B, Joosten KF, Hazelzet JA: 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. 10.1097/01.CCM.0000072121.61120.D8

    PubMed  Article  Google Scholar 

  5. 5.

    Fourrier F, Leclerc F, Aidan K, Sadik A, Jourdan M, Tournois A, et al.: Combined antithrombin and protein C supplementation in meningococceal purpura fulminans: a pharmacokinetic study. Intensive Care Med 2003, 28: 1081-1087. 10.1007/s00134-003-1784-1

    Article  Google Scholar 

  6. 6.

    Makris PE, Girtovitis F, Papadopulos A, Tamioulaki A, Kosmidou M, Pithara E: Treatment of DIC the role of PC. J Thromb Haemost 2003, 1: P0600.

    Google Scholar 

  7. 7.

    Schellongowski P, Bauer E, Locker G, Frass M, Staudinger T, Knobl P: Treatment of adults with sepsis-induced coagulopathy and purpura fulminans with a plasma-derived protein C concentrate (Ceprotin). Crit Care Med 2003, (suppl 2):P021.

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Baratto, F., Michielan, F., Gagliardi, G. et al. First experiences with protein C concentrate in adult patients with severe sepsis and septic shock associated to low protein C levels: a dose-finding study. Crit Care 9, P192 (2005).

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  • Lactic Acid
  • Septic Shock
  • Peritonitis
  • Severe Sepsis
  • Clinical Reason