Procoagulant Platelets

Abstract

Abnormalities in coagulation are a leading cause of disease and death worldwide because of thrombotic events such as myocardial infarction, stroke, etc. It has been estimated that the cost of treatment of these disorders will rise to >820 billion by the year 2030.1 At the center of thrombus formation is the platelet, a cell that is seen as the cornerstone of hemostasis and thrombosis. Platelets mainly function to secure hemostasis by acting as the band-aids of the blood. They are the first responders to sites of vascular injury, bringing with them a membrane surface that provides the glue for clot formation, and a number of proteins essential for coagulation, as well. Platelet involvement ultimately leads to thrombin generation and clot stabilization through fibrin formation. Article see p 1414 The process of thrombus formation is highly orchestrated, but, although much is known about the steps needed to complete the task, holes in our understanding still exist. At sites of vessel injury where the arterial wall shear rate is high, platelets adhere to von Willebrand factor via the glycoprotein VI receptor and collagen. Subsequently, platelet activation occurs and platelets aggregate together via the fibrinogen (glycoprotein IIb/IIIa) receptor that creates platelet/fibrinogen bridges, leading to thrombus formation.2,3 A subgroup of platelets, however, respond to collagen exposure without glycoprotein IIb/IIIa activation, and instead undergo a direct transformation from resting surveillance cells to active procoagulant cells. This process is characterized by an initial shape change that results in membrane asymmetry and resultant exposure of surface anionic phospholipids including phosphatidylserine (PS). Next, the platelets disintegrate, leading to shedding of procoagulant microparticles that provide further hemostatic support. The mechanism underlying this PS exposure is dependent on cystolic Ca2+ elevation via phospholipase-Cγ and phosphatidylinositol 3-kinase signaling. The exposure of PS results in increased surface …