TABLE 1.
Summary of Studies Involving Protein C and aPC in Children
| Study | Population | Major Findings |
|---|---|---|
| Piccin et al25 | Retrospective study of 21 children with severe sepsis treated with nonactivated plasma-derived protein C | Leukocyte count, prothrombin time, protein C levels, activated partial thromboplastin time, and fibrinogen levels significantly improved. Limb amputation rates decreased. No bleeding events observed |
| Moxon et al26,27 | Postmortem and ex vivo examination of children with cerebral malaria in Malawi, Africa | Plasmodium falciparum induces downregulation of EC protein C receptor as well as protein C and thrombomodulin activation, leading to microvascular thrombosis |
| Dalton et al28 | Randomized controlled trial of aPC of 477 children with severe sepsis in 104 PICUs across 18 countries | Treatment with aPC did not change serum levels of IL-1, IL-6, IL-8, IL-10, TNF, or procalcitonin. Reductions in D-dimer antithrombin-3 complexes were observed |
| Pestaña and de la Oliva29 | Case report of a 10-year-old boy with H1N1 ARDS | Nebulized aPC resulted in improved static lung compliance, P/F ratio, and oxygenation index. The patient survived |
| Kendirli et al30 | Children with severe sepsis or septic shock in Ankara, Turkey | Plasma levels of EC-derived protein C receptor were not related to sepsis severity or mortality |
| Nadel et al31 (RESOLVE) | Randomized controlled trial of aPC in 477 children with severe sepsis in 104 PICUs across 18 countries | No difference in overall mortality or serious bleeding events. A nonsignificant increase in central nervous system bleeds in patients under 60 days old was observed |
| Goldstein et al32 (ENHANCE) | Open, multinational study of aPC in 187 patients with severe sepsis | Lack of control group limited conclusions on efficacy; bleeding was identified as a side effect of aPC treatment |
| Albuali et al33 | Case report of a 3-day-old infant with septic shock and multiorgan failure | Improvement of hemodynamic parameters noted on initiation of aPC infusion. The patient survived with no evidence of bleeding |
| Sajan et al34 | Case report of a 4-month-old infant with septic shock and multiorgan failure | Improvement of hemodynamic parameters noted on initiation of aPC infusion. The patient survived with trace subdural hematomas |
| Barton et al35 | Open-label, multicenter trial of aPC in 82 pediatric patients with sepsis | Pediatric patients with sepsis develop aPC deficiency, and administered aPC displays similar pharmacokinetics as adults |
| de Kleijn et al36 | Randomized controlled trial of protein C concentrate in children with meningococcal septic shock | Protein C infusion was tolerated in 20 children and resulted in increased aPC levels and resolution of coagulation abnormalities |
| Faust et al37 | Observational study of 21 children with meningococcal sepsis | Expression of EC thrombomodulin and protein C receptor were lower, as were plasma levels of aPC in children with sepsis |
ENHANCE, Extended Evaluation of Recombinant Human Activated Protein C; IL, interleukin; P/F, PaO2 to FiO2 ratio; RESOLVE, Researching Sepsis and Organ Dysfunction in Children: A Global Perspective; TNF, tumor necrosis factor.