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Use of protein C concentrate in pediatric patients with sepsis
P Silvani1, A Camporesi, E Licari
1Intensive Care Unit, V. Buzzi Children's Hospital, Milan, Italy. paolo.silvani@tiscali.it
Insights
Protein C (PC) concentrate safely improved coagulation in severe sepsis patients, but did not reduce mortality. Further trials are needed to establish PC
Area of Science:
- Pediatric critical care medicine
- Hematology
- Coagulation disorders
Background:
- Protein C (PC) is vital for regulating coagulation and inflammation.
- PC levels decrease in sepsis, serving as a prognostic indicator.
- Exogenous PC can normalize coagulation imbalances in sepsis without reducing mortality.
Purpose of the Study:
- To evaluate the utilization and effects of Protein C concentrate in pediatric patients with severe sepsis and septic shock.
- To compare outcomes between treated and untreated patients.
Main Methods:
- Retrospective analysis of 29 pediatric patients with severe sepsis/septic shock over one year.
- Comparison of age, severity scores (PIM 2), mortality, and length of stay between groups.
- Analysis of coagulation parameters before and after PC infusion in treated patients.
Main Results:
- Treated patients showed significant improvement in PC activity, PT, PTT, and fibrinogen levels.
- No significant reduction in d-dimer, platelet count, or antithrombin III activity was observed.
- No adverse events were linked to PC concentrate; mortality rates were similar between groups.
Conclusions:
- Protein C concentrate effectively improved coagulation parameters in pediatric severe sepsis/septic shock.
- Current PC treatment protocols in PICUs are often below recommended dosages and duration.
- A large-scale randomized trial is recommended to determine PC's role in reducing mortality in pediatric sepsis.
Aim:
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.
