Abstract
Platelet activation mediates systemic inflammatory response during infection. However, data on platelet reactivity (PR) varies among different settings. We assessed PR along different stages of sepsis and tried to predict for determinants of its variance. In parallel, we evaluated it as an early bedside diagnostic biomarker. This was an observational prospective cohort study. Incoming patients were assorted to distinct groups of uncomplicated infection, sepsis, and severe sepsis/septic shock. A control group of healthy volunteers was used as comparison. PR was assessed using the bedside point-of-care VerifyNow assay, in P2Y12 reaction units (PRU) alongside with levels of major inflammatory markers and whole blood parameters. A total of 101 patients and 27 healthy volunteers were enrolled. PR significantly and reversibly increases during sepsis compared to uncomplicated infection and healthy controls (244 ± 66.7 vs 187.33 ± 60.98, p < 0.001 and 192.17 ± 47.51, p < 0.001, respectively). In severe sepsis, PR did not significantly differ compared to other groups. Sepsis stage uniquely accounts for 15.5% of PR in a linear regression prediction model accounting for 30% of the variance of PR (F = 8.836, p < 0.001). PRU >253 had specificity of 91.2% and sensitivity of 40.8% in discriminating septic from non-septic patients. The addition of PRU to SOFA and qSOFA scores significantly increased their c-statistic (AUC SOFA + PRU, 0.867 vs SOFA, 0.824, p < 0.003 and AUC qSOFA + PRU, 0.842 vs qSOFA, 0.739, p < 0.001), making them comparable (AUC SOFA + PRU vs qSOFA + PRU, p = 0.4). PR significantly and reversibly increases early in sepsis, but seems to exhaust while disease progresses. Bedside assessment of PR can provide robust discriminative accuracy in the early diagnosis of septic patients.
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ΚΑ designed the study, analyzed data, and wrote the manuscript, ST collected samples, IX analyzed the data, AP performed PR measurements, TG and AP performed blood parameter and cytokine measurements, EGB oversaw cytokine measurements and critically corrected the manuscript, and CAG oversaw the study and critically corrected the manuscript.
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This work was funded by Hellenic Institute for the Study of Sepsis
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Our study was carried out in accordance with the ethical guidelines of the 2003 Declaration of Helsinki and we obtained the permission of the Regional Research Ethical Committee of the University General Hospital of Patras (24,958/19–12-2013). All patients provided a written informed consent while in the case of a consciousness disorder the latter was obtained from the next of kin as per national law.
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Written informed consent was also comprised of consent for consequent publication of patient data according to good clinical research practice.
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None of the authors have a commercial or other association that might pose a conflict of interest (e.g., pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding).
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A-D Respective whole blood parameter levels along different stages of sepsis (GIF 195 kb)
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Akinosoglou, K., Theodoraki, S., Xanthopoulou, I. et al. Platelet reactivity in sepsis syndrome: results from the PRESS study. Eur J Clin Microbiol Infect Dis 36, 2503–2512 (2017). https://doi.org/10.1007/s10096-017-3093-6
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DOI: https://doi.org/10.1007/s10096-017-3093-6