Xavier Delabranche1, Jean-Pierre Quenot, Thierry Lavigne, Emmanuelle Mercier, Bruno François, François Severac, Lélia Grunebaum, Madah Mehdi, Fatiha Zobairi, Florence Toti, Ferhat Meziani, Julie Boisramé-Helms. 1. 1Service de Réanimation Médicale, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.2EA 7293, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Faculté de médecine, Université de Strasbourg, Strasbourg, France.3Department of Intensive Care, François Mitterrand University Hospital, Dijon, France.4Lipness Team, INSERM Research Center UMR 866 and LabExLipSTIC, University of Burgundy, Dijon, France.5INSERM CIC 1432, Clinical Epidemiology, University of Burgundy, Dijon, France.6EA 7290, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.7Service de Réanimation Médicale, Centre Hospitalier Universitaire de Tours, Tours, France.8Inserm CIC 1435, Réanimation Polyvalente, CHU Dupuytren, Limoges, France.9Laboratoire de biostatistique et d'informatique médicale, Faculté de médecine, Université de Strasbourg, Strasbourg, France.10Groupe méthode en recherche clinique, service de santé publique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.11Laboratoire d'hématologie et hémostase, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.12UMR 7213 CNRS, Faculté de Pharmacie, Université de Strasbourg, Illkirch, France.
Abstract
OBJECTIVES: Inadequate stratification of septic shock patients may result in inappropriate treatment allocation in randomized clinical trials, especially regarding anticoagulant. We previously reported that endothelial-derived microparticles are relevant biomarkers of sepsis-induced disseminated intravascular coagulation. In this validation cohort, we assess microparticles as surrogates of cell activation to improve early disseminated intravascular coagulation diagnosis and patient stratification. DESIGN: Prospective observational study in septic shock patients. SETTINGS: Four medical ICUs in university hospitals. PATIENTS AND METHODS: Two hundred sixty-five patients with septic shock from four ICUs were consecutively enrolled. Disseminated intravascular coagulation was diagnosed according to Japanese Association for Acute Medicine 2006 score. Endothelial- and leukocyte-derived circulating procoagulant microparticles were isolated and quantified by prothrombinase assay at admission, day 3, and day 7. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-nine patients were analyzed. Sixty-one had disseminated intravascular coagulation at admission, and 32 developed disseminated intravascular coagulation during the first 24 hours after admission. Multiple logistic regression model confirmed that endothelial cell-derived microparticles were associated with disseminated intravascular coagulation: CD105-microparticles (odds ratio, 2.13) and CD31-microparticles (odds ratio, 0.65) (p < 0.05). Furthermore, CD11a-microparticles to leukocyte ratio evidenced leukocyte activation (odds ratio, 1.59; p < 0.05). Prediction of disseminated intravascular coagulation was also analyzed after exclusion of patients with disseminated intravascular coagulation at admission. A new multiple logistic regression analysis demonstrated the association of CD105-microparticles (> 0.60 nM eq. PhtdSer; odds ratio, 1.67; p < 0.01), platelets count (≤ 127 g/L; odds ratio, 0.99; p < 0.01), and prothrombin time (≤ 58%; odds ratio, 0.98; p < 0.05) with disseminated intravascular coagulation. A combining score at admission is predictive of the absence of disseminated intravascular coagulation (area under the curve, 72.9%; specificity, 71.2%; sensitivity, 71.0%, with a negative predictive value of 93.1% and a positive predictive value of 31.0%). CONCLUSIONS: Procoagulant microparticles from endothelial cells and leukocytes reflect a vascular injury during sepsis-induced disseminated intravascular coagulation that precedes obvious activation of coagulation. A combination of prothrombin time, endothelium-derived CD105-microparticles, and platelet count at admission could predict the absence of disseminated intravascular coagulation and allow a better stratification in future randomized clinical trials.
OBJECTIVES: Inadequate stratification of septic shockpatients may result in inappropriate treatment allocation in randomized clinical trials, especially regarding anticoagulant. We previously reported that endothelial-derived microparticles are relevant biomarkers of sepsis-induced disseminated intravascular coagulation. In this validation cohort, we assess microparticles as surrogates of cell activation to improve early disseminated intravascular coagulation diagnosis and patient stratification. DESIGN: Prospective observational study in septic shockpatients. SETTINGS: Four medical ICUs in university hospitals. PATIENTS AND METHODS: Two hundred sixty-five patients with septic shock from four ICUs were consecutively enrolled. Disseminated intravascular coagulation was diagnosed according to Japanese Association for Acute Medicine 2006 score. Endothelial- and leukocyte-derived circulating procoagulant microparticles were isolated and quantified by prothrombinase assay at admission, day 3, and day 7. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-nine patients were analyzed. Sixty-one had disseminated intravascular coagulation at admission, and 32 developed disseminated intravascular coagulation during the first 24 hours after admission. Multiple logistic regression model confirmed that endothelial cell-derived microparticles were associated with disseminated intravascular coagulation: CD105-microparticles (odds ratio, 2.13) and CD31-microparticles (odds ratio, 0.65) (p < 0.05). Furthermore, CD11a-microparticles to leukocyte ratio evidenced leukocyte activation (odds ratio, 1.59; p < 0.05). Prediction of disseminated intravascular coagulation was also analyzed after exclusion of patients with disseminated intravascular coagulation at admission. A new multiple logistic regression analysis demonstrated the association of CD105-microparticles (> 0.60 nM eq. PhtdSer; odds ratio, 1.67; p < 0.01), platelets count (≤ 127 g/L; odds ratio, 0.99; p < 0.01), and prothrombin time (≤ 58%; odds ratio, 0.98; p < 0.05) with disseminated intravascular coagulation. A combining score at admission is predictive of the absence of disseminated intravascular coagulation (area under the curve, 72.9%; specificity, 71.2%; sensitivity, 71.0%, with a negative predictive value of 93.1% and a positive predictive value of 31.0%). CONCLUSIONS: Procoagulant microparticles from endothelial cells and leukocytes reflect a vascular injury during sepsis-induced disseminated intravascular coagulation that precedes obvious activation of coagulation. A combination of prothrombin time, endothelium-derived CD105-microparticles, and platelet count at admission could predict the absence of disseminated intravascular coagulation and allow a better stratification in future randomized clinical trials.
Authors: David M Smadja; Steven J Mentzer; Michaela Fontenay; Mike A Laffan; Maximilian Ackermann; Julie Helms; Danny Jonigk; Richard Chocron; Gerald B Pier; Nicolas Gendron; Stephanie Pons; Jean-Luc Diehl; Coert Margadant; Coralie Guerin; Elisabeth J M Huijbers; Aurélien Philippe; Nicolas Chapuis; Patrycja Nowak-Sliwinska; Christian Karagiannidis; Olivier Sanchez; Philipp Kümpers; David Skurnik; Anna M Randi; Arjan W Griffioen Journal: Angiogenesis Date: 2021-06-28 Impact factor: 9.596