Platelet adhesive receptors and novel anti-thrombotics

Abstract

The Role of Platelets in Haemostasis and Arterial Thrombosis There is a wealth of clinical and experimental evidence demonstrating a crucial role for platelets in normal haemostasis and in the development of arterial thrombi. The earliest event in the haemostatic process involves the adhesion of platelets to the site of vessel wall injury. An exaggerated haemostatic response at sites of atherosclerotic plaque rupture can however lead to the development of vaso-occlusive thrombi. Hence a thorough understanding of the interaction between platelets and the subendothelium is essential to understand fully the processes of haemostasis and thrombogenesis. Considerable progress in this area of research in the past decade has resulted in the development of several new antithrombotic agents which are gradually making their way into routine clinical practice. Platelet adhesion requires multiple receptor-ligand interactions The process of platelet adhesion to the subendothelium is intricate and complex. This dynamic process requires the arrest of rapidly circulating platelets onto areas of denuded endothelium. Platelet adhesion is mediated by several distinct platelet receptors which interact with a variety of adhesive proteins present within the subendothelial matrix. The initial contact of platelets with the injured vessel wall involves the binding of platelets to subendothelial-bound von Willebrand factor (vWf) and collagen. vWf interacts with a specific platelet receptor complex known as glycoprotein Ib-V-IX which is absent in patients with the hereditary platelet bleeding disorder Bernard Soulier syndrome. The collagen receptor is