Model for the procoagulant properties of platelet CD36/ERK5 signaling. In dyslipidemic conditions, circulating oxidized lipids present in oxLDL particles are recognized by platelet CD36. This promotes immediate recruitment of Src family kinases and generation of ROS by NADPH oxidase. Activation of MAPK ERK5 signaling by superoxide anion, and hydrogen peroxide promotes the apoptosome formation and caspase activity. The mechanisms of activating ERK5 by ROS are unclear. Caspases activate known scramblases present on the surface of the membrane and thus promote externalization of procoagulant phosphatidylserine. ERK5 also induces a signaling pathway that promotes integrin activation to enhance thrombosis. There is crosstalk between CD36 and GPVI downstream signaling, potentially through Src family kinases, ERK5, or calcium. This crosstalk enhances the externalization of phosphatidylserine through maladaptive apoptosome formation that is not common to the cyclophilin D/mPTP pathway induced by the strong agonists THR and CVX or the physiologic cell death pathway. Assembly of the prothrombinase and tenase complex to the anionic phospholipid enhances fibrin accumulation in vivo to support arterial thrombosis in dyslipidemic conditions.