Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis.

PURPOSE: The endothelial protein C receptor (EPCR) negatively regulates the coagulopathy and inflammatory response in sepsis. Mechanisms controlling the expression of cell-bound and circulating soluble EPCR (sEPCR) are still unclear. Moreover, the clinical impact of EPCR shedding and its potential value to predict sepsis progression and outcome remain to be established. METHODS: We investigated the time course of plasma sEPCR over the 5 first days (D) of severe sepsis in 40 patients. RESULTS: No significant difference was observed when comparing sEPCR at admission (D1) to healthy volunteers and to patients with vasculitis. We report that the kinetics profile of plasma sEPCR in patients was almost stable at the onset of sepsis with no change from D1 to D4 and then a significant decrease at D5. This pattern of release was consistently observed whatever the level of sEPCR at D1. Characteristics of patients or of infections (except Gram negative) had no or little critical influence on the sEPCR profile. However, we found that sEPCR kinetics was clearly associated with patient's outcome (D28 survival). We demonstrate that a significant but moderate (<15% of basal level) and transient increase in sEPCR level at D2 is associated with poor outcome at D28. CONCLUSION: Severe sepsis, at the onset, only triggers moderate quantitative changes in plasma sEPCR levels. Our findings suggest that in severe sepsis, an early (at D2), transient but significant increase in circulating sEPCR may be detrimental suggesting that sEPCR could provide an early biological marker of sepsis outcome.

Keywords

soluble EPCR severe sepsis gender infection survival analysis

Domains

Cellular Biology Infectious diseases

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inserm-00582321_edited.pdf (246.05 Ko)

EPCR_Intens_Care_med_version_5_Final_01_02_2011.pdf (625.34 Ko)

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ESM_2.pdf (42.59 Ko)

ESM_3.pdf (17.72 Ko)

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https://www.hal.inserm.fr/inserm-00582321

Submitted on : Friday, April 1, 2011-7:57:48 AM

Last modification on : Wednesday, April 27, 2022-3:43:17 AM

Long-term archiving on: Saturday, December 3, 2016-1:41:12 PM

Dates and versions

inserm-00582321 , version 1 (01-04-2011)

Identifiers

HAL Id : inserm-00582321 , version 1
DOI : 10.1007/s00134-011-2171-y
PUBMED : 21394629

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Christophe Guitton, Nathalie Gérard, Véronique Sébille, Cédric Bretonnière, Olivier Zambon, et al.. Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis.: Profiling soluble EPCR upon severe sepsis. Intensive Care Med, 2011, 37 (6), pp.950-6. ⟨10.1007/s00134-011-2171-y⟩. ⟨inserm-00582321⟩

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