Schematic illustration of the proposed EC- and platelet-mediated processes fueling coagulation and vascular inflammation in the setting of Pon2^−/−. Endothelial TF procoagulant activity is promoted by Pon2^−/−-mediated endothelial redox mechanisms (increased formation of ROS, exposure of PS and lipid peroxidation [Lipid perox]) and reduced endothelial TFPI, leading to generation of thrombin, which mediates fibrin formation and platelet activation. Pon2 knockout in platelets contributes to enhanced coagulation via redox mechanisms. EC-mediated systemic inflammation is established by increased IL-6 levels, potentially contributing procoagulant state as well as vascular inflammation and dysfunction.