title: Use of protein C concentrate in pediatric patients with sepsis.
abstract: OBJECTIVE
  Protein C (PC) is a plasma glycoprotein implicated in modulating coagulation and inflammation. Its levels decrease in sepsis and related diseases, where it has also proved to be a prognostic indicator of outcome. Infusion of exogenous PC, although not able to decrease mortality in severe sepsis and septic shock, can safely resolve the coagulation imbalances related to these pathological states.
  
  
  METHODS
  A retrospective study was performed about utilisation of PC in severe sepsis and septic shock patients in three italian PICUs during a one-year period. Data from 29 patients were analysed. Age, PIM 2, mortality and length of stay were compared between treated and non treated patients. Treated patients were also analysed for PC dosage received, length of treatment, and modification of hemocoagulation parameters, before PC infusion and every 24 hours.
  
  
  RESULTS
  In treated patients, the activity of PC, PT and PTT activity and fibrinogen improved significantly from basal to day 5 (p<0.05). Diminution of d-dimer was not quite significant (p=0.0514). Rise in platelets count and antithrombin III activity was not significant. No adverse reactions related to Protein C concentrate were observed. No difference in mortality was observed between the two groups.
  
  
  CONCLUSIONS
  Although PC is included in guidelines for management of severe sepsis and septic shock, only 38%, of observed patients received PC treatment. Even in the treated group, patients received a lower dosage of PC, and for a shorter period, than recommended. In accordance to previous studies, we did not observe differences in mortality between treated and untreated patients. Our results showed a significant increase in plasma PC activity, following infusion of PC concentrate. This increase in PC appeared sufficient to restore some, but not all, of the abnormalities in the coagulation system. A large randomized, phase 3, placebo-controlled trial in children with severe sepsis and septic shock is advisable to establish effective role of therapy with PC in reducing mortality of these patients.
authors.affiliation: Intensive Care Unit, V. Buzzi Children's Hospital, Milan, Italy. paolo.silvani@tiscali.it
authors.forename: P
authors.initials: P
authors.lastname: Silvani
authors.forename: A
authors.initials: A
authors.lastname: Camporesi
authors.forename: E
authors.initials: E
authors.lastname: Licari
authors.forename: A
authors.initials: A
authors.lastname: Wolfler
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001780:Blood Coagulation Tests; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011486:Protein C / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy*; D012772:Shock, Septic / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D011486:Protein C; D011994:Recombinant Proteins