Abstract
BackgroundThis study investigated changes in plasma level of soluble endothelial protein C receptor (sEPCR) in association with outcome in patients with septic shock. We explored sEPCR for early sepsis prognosis assessment and constructed a scoring system based on clinical and biological data, in order to discriminate between surviving at hospital discharge and non-surviving patients.MethodsClinical data and samples were extracted from the prospective “STREPTOGENE” cohort.We enrolled 278 patients, from 50 intensive care units (ICUs), with septic shock caused by pneumococcal pneumonia. Patients were divided into survivors (n = 194) and non-survivors (n = 84) based on in-hospital mortality. Soluble EPCR plasma levels were quantified at day 1 (D1) and day 2 (D2) by ELISA. The EPCR gene A3 haplotype was determined. Patients were followed up until hospital discharge. Univariate and multivariate analyses were performed. A scoring system was constructed using least absolute shrinkage and selection operator (lasso) logistic regression for selecting predictive variables.ResultsIn-hospital mortality was 30.2% (n = 84). Plasma sEPCR level was significantly higher at D1 and D2 in non-surviving patients compared to patients surviving to hospital discharge (p = 0.0447 and 0.0047, respectively). Early increase in sEPCR at D2 was found in non-survivors while a decrease was observed in the survival group (p = 0.0268). EPCR A3 polymorphism was not associated with mortality. Baseline sEPCR level and its variation from D1 to D2 were independent predictors of in-hospital mortality. The scoring system including sEPCR predicted mortality with an AUC of 0.75.ConclusionsOur findings confirm that high plasma sEPCR and its increase at D2 are associated with poor outcome in sepsis and thus we propose sEPCR as a key player in the pathogenesis of sepsis and as a potential biomarker of sepsis outcome.
Highlights
This study investigated changes in plasma level of soluble endothelial protein C receptor in association with outcome in patients with septic shock
A possible explanation for these discrepancies is the bimodal distribution of soluble endothelial protein C receptor (sEPCR) levels related to the A3 haplotype, as this gene polymorphism was associated with high levels of sEPCR
The prognostic score was the sum of the product between the weights and the normalized explicative variables sEPCR soluble endothelial protein C receptor, SOFA Sepsis-related Organ Failure Assessment, SAPS Simplified Acute Physiology Score
Summary
This study investigated changes in plasma level of soluble endothelial protein C receptor (sEPCR) in association with outcome in patients with septic shock. Severe sepsis is a frequent and serious disease in intensive care units (ICUs). It remains a leading cause of death in critically ill patients, despite efforts to improve patient outcomes [1]. The protein C (PC) anticoagulant pathway is a major system that prevents coagulation, and its impairment influences outcome in sepsis. This pathway involves two soluble proteins: PC and protein S, and two endothelial receptors: thrombomodulin (TM) and the endothelial protein C receptor (EPCR). Disruption of the EPCR gene in mice causes placental thrombosis and embryonic lethality, confirming a key role for EPCR in controlling coagulation [10]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
