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Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy

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Abstract

Purpose

Septic shock-induced disseminated intravascular coagulopathy (DIC) contributes to multiple organ failure. Mechanisms governing vascular responses to open occurrence of DIC have not yet been established. Circulating plasma microparticles (MPs), released upon cell stress, constitute a catalytic procoagulant surface and are surrogates of vascular cell activation/injury. Herein, MPs were assessed as possible markers of haemostatic and vascular dysfunction in the DIC time course.

Methods

One hundred patients with septic shock from three ICUs were enrolled and their haemostatic status evaluated at admission (D1), D2, D3 and D7. Circulating procoagulant MPs were isolated, quantified by prothrombinase assay and their cellular origin determined. DIC diagnosis was made according to the JAAM 2006 score.

Results

Ninety-two patients were analysed and 40 had DIC during the first 24 h. Routine clotting times and factor/inhibitor activity did not allow assessing vascular cell involvement. At admission, thrombin generation and fibrinolysis were observed in both groups while impaired fibrin polymerisation was evidenced only in DIC patients. Sustained thrombin generation persisted over time in both groups at D7. While total microparticle concentrations were in the same range regardless of DIC diagnosis, specific phenotypes were already detected at admission in DIC patients. Endothelial- and leucocyte-derived MPs were higher in DIC while an increased soluble glycoprotein V/platelet ratio was delayed, underscoring the first involvement of endothelial cells and leucocytes whereas platelet activation was delayed. Endothelium-derived CD105-MPs (OR 6.55) and CD31-MPs (OR 0.49) were strongly associated with early DIC in multivariate analysis.

Conclusion

Endothelial-derived microparticles are relevant biomarkers of septic shock-induced DIC and could be used to evaluate early vascular injury.

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Acknowledgments

XD, FT and FM had full access to all the study data and take responsibility for their integrity and the accuracy of the analysis. XD, FT, JMF and FM participated in the study design and obtained funding for the study. XD, PA, YM, JHB, AB and FM collected the data. XD, TL, FT and FM analysed the data; TL provided statistical expertise. XD, JHB, AB, LG, FL and FT performed biological analyses. XD, FT, FL and FM drafted the report, and the report was revised for important intellectual content by XD, PA, LG, CG, JMF, FT and FM. All authors read and approved the final manuscript.

We would like to thank Fatiha Zobairi for sample preparation and MP measurements, Jacqueline Picard for routine haemostasis tests, Sylvie Moog for sGPV analysis, François Lefebvre (MD) for complementary statistical analysis and Maleka Schenck-Dhif (MD) and Dominique Desprez (MD) for manuscript revision and Pierre Pothier for careful English proofreading of the manuscript.

This work was supported by grants from the French Ministry of Health (Projet Hospitalier de Recherche Clinique, Hôpitaux Universitaires de Strasbourg no. 4649), Laboratoire Français de Fractionnement et des Biotechnologies (LFB SA, Les Ullis, France), the Société de Réanimation de Langue Française (SRLF, Paris, France) and the Association pour le Développement et la Recherche en Réanimation (ADRER, Strasbourg, France).

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The authors declare that they have no conflicts of interest.

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Correspondence to Ferhat Meziani.

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Clinicaltrial.gov identifier NCT 01604551

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Delabranche, X., Boisramé-Helms, J., Asfar, P. et al. Microparticles are new biomarkers of septic shock-induced disseminated intravascular coagulopathy. Intensive Care Med 39, 1695–1703 (2013). https://doi.org/10.1007/s00134-013-2993-x

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