Hypercholesterolemia is a risk factor for atherothrombotic disease by promoting platelet production and activation. Hypercholesterolemia promotes megakaryopoiesis, platelet (PLT) biogenesis, and myelopoiesis, leading to leukocytosis. Hypercholesterolemia also increases platelet activation, likely by elevating platelet production and by direct impact on platelets. Activated platelets form PLAs, which are further increased in leukocytosis. PLA is an independent risk factor for atherothrombotic disease. GMP, guanosine monophosphate; HSC, hematopoietic stem cell; MkP, megakaryocyte progenitor cell.