Are Baseline Levels of Gas6 and Soluble Mer Predictors of Mortality and Organ Damage in Patients with Sepsis? The Need-Speed Trial Database.

Francesco Gavelli,Salvatore Di Somma,Maria Lorenza Muiesan,Mattia Bellan,Nicola Fiotti,Gianni Biolo,Luca Molinari,Marco Baldrighi,Enrico Lupia,Filippo Mearelli,Gian Carlo Avanzi,Livia Salmi,Pier Paolo Sainaghi,Luigi Mario Castello,Filippo Patrucco,Efrem Colonetti,Chiara Airoldi

doi:10.3390/biomedicines10020198

Abstract

Soluble tyrosine kinase receptor Mer (sMer) and its ligand Growth arrest-specific protein 6 (Gas6) are predictors of mortality in patients with sepsis. Our aim is to clarify whether their measurement at emergency department (ED) presentation is useful in risk stratification. We re-analyzed data from the Need-Speed trial, evaluating mortality and the presence of organ damage according to baseline levels of sMer and Gas6. 890 patients were eligible; no association with 7- and 30-day mortality was observed for both biomarkers (p > 0.05). sMer and Gas6 levels were significantly higher in acute kidney injury (AKI) patients compared to non-AKI ones (9.8 [4.1–17.8] vs. 7.9 [3.8–12.9] ng/mL and 34.8 [26.4–47.5] vs. 29.8 [22.1–41.6] ng/mL, respectively, for sMer and Gas6), and Gas6 also emerged as an independent AKI predictor (odds ratio (OR) 1.01 [1.00–1.02]). Both sMer and Gas6 independently predicted thrombocytopenia in sepsis patients not treated with anticoagulants (OR 1.01 [1.00–1.02] and 1.04 [1.02–1.06], respectively). Moreover, sMer was an independent predictor of both prothrombin time-international normalized ratio (PT-INR) > 1.4 (OR 1.03 [1.00–1.05]) and sepsis-induced coagulopathy (SIC) (OR 1.05 [1.02–1.07]). An early measurement of the sMer and Gas6 plasma concentration could not predict mortality. However, the biomarkers were associated with AKI, thrombocytopenia, PT-INR derangement and SIC, suggesting a role in predicting sepsis-related organ damage.

Highlights

The aim of this secondary analysis was to evaluate the prognostic value of Growth arrest-specific protein 6 (Gas6) and Soluble tyrosine kinase receptor Mer (sMer) plasma concentrations in patients with sepsis at the emergency department (ED) presentation, defined according to the presence both of systemic inflammatory response syndrome (SIRS) [24] and clinical or microbiologic signs of infection, in terms of mortality and organ damage development
Gas6 was measured in patients (97%) and sMer in patients (96%), and their median plasmatic levels were
Two studies involving critically ill patients admitted to intensive care unit (ICU) with sepsis or septic shock showed that Gas6 and Mer were associated with increased mortality [20,21]

Summary

Introduction

Biomedicines 2022, 10, 198 ranges between 17% and 26% [1] Both a prompt diagnosis and prognostic assessment are necessary when sepsis is suspected in the Emergency Department (ED). Risk stratification permits one to identify septic patients at a higher risk of mortality or severe organ damage, who may need early intensive care unit (ICU) admission [3,4]. To improve both the accuracy and speed of the diagnostic process, as well as the early prognostic stratification of septic patients in the ED, many biomarkers, such as c-reactive protein, procalcitonin and lactate, have been proposed. Other biomarkers have been tested, alone or in combination [14–18]; the ideal biomarker is still lacking

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