Monday, 17 September 2018 19:13

Platelet activation and prothrombotic properties in a mouse model of peritoneal sepsis

doi:  10.1038/s41598-018-31910-8

 

Fanny Vardon Bounes,1,2 Vincent Mémier,1,3 Marina Marcaud,1 Aemilia Jacquemin,1,2 Hind Hamzeh-Cognasse,4 Cédric Garcia,3 Jennifer Series,3 Pierre Sié,1,3 Vincent Minville,1,2 Marie-Pierre Gratacap,1 Bernard Payrastre1,3


1INSERM, U1048 et Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Toulouse, 31400 France
2Anesthesiology and Critical Care Unit, Centre hospitalier universitaire de Toulouse, Toulouse, 31400 France
3Haematology laboratory, Centre hospitalier universitaire de Toulouse, Toulouse, 31400 France
4EA3064-GIMAP, Université de Lyon, Saint-Etienne, 42023 France

 

Abstract

Sepsis is associated with thrombocytopenia and microvascular thrombosis. Studies have described platelets implication in this pathology but their kinetics of activation and behavior remain poorly known. We show in a mouse model of peritonitis, the appearance of platelet-rich thrombi in organ microvessels and organ damage. Complementary methods are necessary to characterize platelet activation during sepsis as circulating soluble markers and platelet-monocyte aggregates revealed early platelet activation, while surface activation markers were detected at later stage. A microfluidic based ex-vivo thrombosis assay demonstrated that platelets from septic mice have a prothrombotic behavior at shear rate encountered in microvessels. Interestingly, we found that even though phosphoinositide-3-kinase β−deficient platelet mice formed less thrombi in liver microcirculation, peritoneal sepsis activates a platelet alternative pathway to compensate the otherwise mandatory role of this lipid-kinase to form stable thrombi at high shear rate. Platelets are rapidly activated during sepsis. Thrombocytopenia can be attributed in part to platelet-rich thrombi formation in capillaries and platelet-leukocytes interactions. Platelets from septic mice have a prothrombotic phenotype at a shear rate encountered in arterioles. Further studies are necessary to unravel molecular mechanisms leading to this prothrombotic state of platelets in order to guide the development of future treatments of polymicrobial sepsis.