Platelet turnover in atherothrombotic disease

Platelets play a pivotal role in primary hemostasis where their rapid response to vascular injury prevents excessive bleeding. To accomplish this, platelets are enriched in membrane receptors and cytoplasmic enzymes with often redundant and self-amplifying functions leading to platelet activation, release into the bloodstream of hemostatically active compounds and culminating with thrombus formation. However, the same process in the pathological state of atherosclerosis can lead to thrombotic complications such as an acute coronary syndrome or stroke. The role of platelets in this process is more extensive than previously believed. Several lines of evidence suggest that platelets contribute not only to the acute thrombotic events in atherosclerosis, but also to disease initiation and progression. This review focuses on the role of platelet heterogeneity and turnover in atherothrombotic disease. Specifically, this article covers (a) the regulation of platelet formation; (b) the role of the heterogeneity of platelets in atherothrombotic diseases; (c) the disease-modifying effect of platelets on the development of atherosclerosis; and (d) the modifying effect of atherosclerotic disease on platelet production and function; (e) the platelet indices influencing platelet responsiveness to antiplatelet therapies; and finally (f) the potential novel therapeutic modalities that could be applied in atherothrombosis.