Protein C concentrate to restore physiological values in adult septic patients

Objective: To describe the efficacy and safety of protein C (PC) concentrate to restore physiological values in adult septic patients having clinical contraindications to activated PC. Design: Case series (pilot study). Setting: Three adult ICUs of a University Hospital. Patients and participants: Twenty adult patients affected by severe sepsis or septic shock with plasma values of PC < 50%. Interventions: Patients were treated with PC concentrate (Ceprotin (R)-Baxter) with a starting bolus followed by a continuous infusion for 72 h [3 IU/(kg h)]. Measurements and results: PC activity, WBC, platelets, D-Dimer, fibrinogen, PT, aPTT, AT III, lactate, Sepsis-related Organ Failure Assessment (SOFA), Disseminated Intravascular Coagulation (DIC) score, adverse events, and mortality were measured. Baseline plasma PC activity was 34.5 +/- 9.1%. PC concentrate normalized the PC activity in all patients within 48 h, and then remained stable for the following days. At baseline, several patients showed abnormal PT, aPTT, platelets values, and lactate levels. During the study period, there was a significant increase of platelets, fibrinogen, PT, AT III, and a significant decrease of D-Dimer, aPTT, DIC score, and lactate. No adverse reactions (hemorrhage or thrombosis) were observed. Mortality at 28 days was 35%. Conclusions: Our pilot study shows that the administration of PC concentrate to patients having contraindications to the treatment with activated PC was safe and possibly useful to control the coagulopathy triggered and sustained by sepsis. A randomized, double blind study in patients with severe sepsis and contraindications to activated PC administration would be advisable to state the safety and the possible role of this product in the treatment of severe sepsis.