Protein C Pathway in Paediatric and Neonatal Sepsis
Related Experiment Video
Updated: Oct 3, 2025
A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
Hassan Eliwan1,2, Murwan Omer3, Ellen McKenna2
1National Children's Research Centre, Dublin, Ireland.
Insights
Protein C regulates coagulation and inflammation. While recombinant human activated protein C (rhAPC) showed promise in adult sepsis, its role in pediatric sepsis requires further study due to reduced levels and potential benefits in specific patient groups.
Area of Science:
- Biochemistry
- Immunology
- Critical Care Medicine
Background:
- Protein C is a key regulator of coagulation and inflammation.
- It inactivates coagulation factors Va and VIIIa and inhibits pro-inflammatory cytokines.
- Reduced Protein C levels are observed in pediatric and neonatal sepsis, potentially contributing to thrombosis and organ dysfunction.
Purpose of the Study:
- To evaluate the role of Protein C in pediatric and neonatal sepsis.
- To explore the potential benefits of recombinant human activated protein C (rhAPC) in this patient population.
- To identify patient subgroups who may benefit from Protein C-based therapies.
Main Methods:
- Review of existing clinical and immunological data on Protein C in sepsis.
- Analysis of the impact of rhAPC on mortality and inflammatory markers.
- Consideration of ongoing development of novel rhAPC formulations.
Main Results:
- Previous studies showed rhAPC reduced mortality in adult sepsis, but recent trials yielded no significant benefit.
- Protein C deficiency is linked to severe outcomes in pediatric sepsis, including disseminated intravascular thrombosis and multiorgan dysfunction.
- Newer rhAPC versions aim to reduce hemorrhage risk.
Conclusions:
- The precise role of Protein C in pediatric sepsis warrants further investigation.
- Clinical and immunological evaluations are needed to define patient subgroups for rhAPC therapy.
- Developing safer rhAPC formulations may expand therapeutic applications in sepsis.
Abstract:
Protein C plays a major role in the physiological regulation of coagulation pathways through inactivation of factor Va, factor VIIIa, and plasminogen activator inhibitor. Protein C is involved in the control of inflammation during sepsis, by inhibiting release of pro-inflammatory cytokines, thereby controlling neutrophil, and monocyte effects on injured tissue. Recombinant human activated protein C (rhAPC) reduced mortality in adult sepsis in earlier studies but had no significant benefit in more recent trials. Protein C levels are reduced during paediatric and neonatal sepsis, which may play a major role in the development of disseminated intravascular thrombosis, purpura fulminans, and multiorgan dysfunction. The role of protein C in paediatric sepsis requires further clinical and immunological evaluation to define the patient subgroups who may benefit from this therapy. Newer versions of rhAPC are under development with less risk of haemorrhage potentially broadening the scope of this intervention.
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