Platelet function under high shear conditions

Abstract

Blood platelets are the first line of defense against bleeding and as such involved in the haemostatic repair of damaged vasculature. Their true prowess seems to be displayed under high shear conditions where platelets interact with a variety of plasma proteins, all of which are tightly regulated to close the leak but at the same time prevent lumen occlusion and thromboembolism. The first task is to arrest fast flowing platelets on exposed collagen of the damaged subendothelial surface. Although platelets are endowed with several collagen receptors, most notably integrin alpha2bbeta1 and the immunoglobulin superfamily member GPVI, they can not arrest platelets at high shear rates. The latter requires binding of the platelet receptor GPIbalpha to the A1-binding domain of von Willebrand factor (VWF), which first has to be immobilized from the flowing blood onto the site of injury. Under high shear conditions further accrual of newly arriving platelets again requires VWF, which has to bridge platelets not only to the exposed collagen but also to each other by being sandwiched between the multiple platelet layers of the haemostatic plug.