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

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Abstract

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.

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Abbreviations

APC:

Activated protein C

EC:

Endothelial cell

EPCR:

Endothelial protein C receptor

ICU:

Intensive care unit

MPA:

Microscopic polyangiitis

PC:

Protein C

SAPS:

Simplified Acute Physiology Score

mEPCR:

Membrane EPCR

sEPCR:

Soluble EPCR

SIRS:

Systemic inflammatory response syndrome

SOFA:

Sepsis-related Organ Failure Assessment

TF:

Tissue factor

TM:

Thrombomodulin

TNFα:

Tumor necrosis factor-alpha

WG:

Wegener granulomatosis

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Acknowledgments

This work was supported by grants from l’Agence de Biomédecine, La Société de Néphrologie, l’Association pour le Développement de la Réanimation (ADR, Nantes), Lilly-France. This work was also in part supported by XENOME, an EU-funded Integrated Project in Life Sciences, Genomics and Biotechnology for Health (LSHB-CT-2006-037377) and by a grant from la Fondation de l’Avenir (contrat ET8-498).

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. INSERM UMR643, Institut de Transplantation et de Recherche en Transplantation, ITERT, CHU Nantes, 44000, Nantes, France

    Christophe Guitton, Nathalie Gérard & Béatrice Charreau

  2. UMR643, Faculté de Médecine, Université de Nantes, 44000, Nantes, France

    Christophe Guitton, Nathalie Gérard & Béatrice Charreau

  3. Service de Réanimation Médicale Polyvalente, Hôtel Dieu, CHU de Nantes, 30 Boulevard Jean Monnet, 44093, Nantes Cedex 1, France

    Christophe Guitton, Cédric Bretonnière, Olivier Zambon & Daniel Villers

  4. EA 4275, Faculté de Pharmacie, Université de Nantes, 44000, Nantes, France

    Véronique Sébille

  5. Plateforme de Biométrie, CHU de Nantes, 44000, Nantes, France

    Véronique Sébille

Authors
  1. Christophe Guitton
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  2. Nathalie Gérard
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  3. Véronique Sébille
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Correspondence to Christophe Guitton.

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Guitton, C., Gérard, N., Sébille, V. et al. Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis. Intensive Care Med 37, 950–956 (2011). https://doi.org/10.1007/s00134-011-2171-y

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