Alexandre Bedet1,2, Keyvan Razazi1,2, Florence Boissier1,2, Mathieu Surenaud3,4, Sophie Hue3,4, Stéphane Giraudier5, Christian Brun-Buisson1,2, Armand Mekontso Dessap1,2. 1. Service de Réanimation Médicale, Hôpitaux Universitaires Henri Mondor, Hôpitaux de Paris, DHU A-TVB, Créteil, France. 2. Groupe de Recherche Clinique CARMAS, Institut Mondor de Recherche Biomédicale, Faculté de Médecine de Créteil, Université Paris Est Créteil, Créteil, France. 3. Institut Mondor de Recherche Biomédicale, Faculté de Médecine, Université Paris Est Créteil, Equipe 16, Créteil, France. 4. Service d'immunologie, Hôpitaux Universitaires Henri Mondor, Hôpitaux de Paris, Créteil, France. 5. Service d'hématologie biologique, Hôpitaux Universitaires Henri Mondor, Hôpitaux de Paris, Créteil, France.
Abstract
BACKGROUND: Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. METHODS: Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded. RESULTS: Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia. CONCLUSION: Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.
BACKGROUND:Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during humanseptic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. METHODS: Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded. RESULTS:Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia. CONCLUSION: Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.
Authors: Erik K Amundsen; Christina Binde; Erik E Christensen; Olav Klingenberg; Dag Kvale; Aleksander R Holten Journal: Crit Care Explor Date: 2021-07-16