Inhibitors of platelet adhesion to VWF and collagen

Abstract

Platelets play an essential role in thrombotic and hemostatic processes. Upon injury, platelets first adhere to the exposed extracellular matrix, predominantly via interactions with collagen and von Willebrand factor (VWF), resulting in hemostatic plug formation. Uncontrolled thrombus formation however results in occlusive complications leading to, e.g., myocardial infarction and ischemic stroke. New and more targeted antiplatelet therapies are essential to prevent such thrombotic complications. In this chapter, we describe different compounds that inhibit initial platelet adhesion. These include compounds that interfere with binding of VWF to collagen or platelet glycoprotein (GP) Ib and molecules that prevent platelet adhesion to collagen via blockade of either GPVI or integrin α2β1. Results from the different preclinical animal and clinical patient studies demonstrate that inhibition of these interactions holds great promise as an antithrombotic strategy without significant increase of the bleeding risk.