Platelet-vessel wall interactions and drug effects

Platelet-vessel wall interaction is necessary for hemostasis and vascular repair, but also plays a fundamental role in the early and late development of atherosclerosis and atherothrombotic vascular events. A plethora of adhesion molecules, biological mediators and receptors are engaged in the regulation of platelet function in hemostasis and thrombosis. Currently available antiplatelet drugs act on targets that are critical for both, physiological hemostasis and pathological intravascular thrombosis. Consequently, their major disadvantage is bleeding complications, especially when different antiplatelet drugs are combined or applied together with anticoagulants, such as in antithrombotic therapy of acute coronary syndromes. Aspirin, clopidogrel and GPIIb/IIIa antagonists are commonly used inhibitors of platelet aggregation or secretion. In addition, they modify platelet interactions with the vessel wall, which may contribute to or modulate their antithrombotic action. Some commonly used drugs without primary antiplatelet effects, such as heparins or statins, also appear to modify platelet interaction with the vessel wall. Present research on antithrombotic drug targets aims to identify new pharmacological concepts which more specifically address the pathophysiological mechanisms leading to intravascular thrombosis, thus intending to reduce interference with hemostasis.This review article summarizes the biological and pathological mechanisms involved in thrombogenic platelet-vessel wall interaction, describes the current knowledge on the clinically available drugs in this field and gives an outlook on emerging concepts and innovative pharmacological compounds, which may improve efficacy and safety of antiplatelet therapy in the future.