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Review
. 2025 Apr 14;5(1):21.
doi: 10.1186/s44158-025-00243-0.

Protein C in adult patients with sepsis: from pathophysiology to monitoring and supplementation

Irene Coloretti  1 , Antonio Corcione  2 , Gennaro De Pascale  3   4 , Abele Donati  5   6 , Francesco Forfori  7 , Marco Marietta  8 , Mauro Panigada  9 , Paolo Simioni  10 , Carlo Tascini  11   12 , Pierluigi Viale  13   14 , Massimo Girardis  15
Affiliations
Review

Protein C in adult patients with sepsis: from pathophysiology to monitoring and supplementation

Irene Coloretti et al. J Anesth Analg Crit Care. .

Abstract

Protein C (PC) plays a crucial role in modulating inflammation and coagulation in sepsis. Its anticoagulant and cytoprotective properties are critical in mitigating sepsis-induced coagulopathy, which is associated with high mortality rates. In sepsis, low levels of PC are associated with an elevated risk of multiple organ dysfunction and increased mortality. Routine monitoring of PC levels is not widely implemented but appears relevant in selected populations, such as patients with purpura fulminans, sepsis-induced coagulopathy (SIC), disseminated intravascular coagulopathy (DIC) or hyperinflammatory septic shock phenotypes. Treatment with PC has been limited to PC concentrate approved for paediatric use in congenital PC deficiencies and purpura fulminans, while the efficacy of PC supplementation in sepsis remains a subject of debate. Considering the physiological significance of PC and its role in sepsis pathophysiology, additional studies are necessary to fully elucidate its therapeutic efficacy in specific clinical settings.

Keywords: Activated protein C; Disseminated intravascular coagulation; Sepsis; Septic shock; Thrombosis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: IC, AC, GDP, AD, FF, MM, MP, PS, PV, GM have no conflict of interest to declare.CT has received in the last 2 years research grants and/or been a consultant and/or received a fee for speaking from Angelini, Correvio, Biotest, GSK, Gilead, HIKMA, BioMerieux, MSD, Novartis, Nordic Pharma, Pfizer, Shionogi, Thermofisher, Zambon, Diasorin.

Figures

Fig. 1
Fig. 1
Proposed clinical scenarios for measuring protein C in critically ill patients and proposed indications for PC concentrate treatment in specific subpopulations
See this image and copyright information in PMC

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