Circulating procoagulant microparticles in patients with venous thromboembolism

Abstract

Circulating microparticles (MPs) are small vesicles released from the membrane of almost all cells as a result of cell activation or apoptosis [1–4]. They have a size of less than 1 μmand theirmembrane consists mainly of phospholipids and proteins. MPs are generated under physiological conditions in healthy individuals and display an integral function in the process of coagulation, inflammation, cell remodelling and proliferation [4,5]. MPs play an important role in the initiation and propagation of coagulation [1]. Increasing evidence suggests that MPs are involved in the pathomechanism of thrombotic disease [1–4]. It has been demonstrated that MPs initiate thrombin generation [5]. One major hallmark is the exposure of phosphatidylserine (PS) on MPs that enables the assembly of clotting factors on their surface necessary for the formation of the prothrombinaseand tenase-complex [6–10]. In resting cells aminophospholipids such as PS aremainly sequestrated in the inner leaflet of the plasmamembrane, whereas sphingomyelin and phosphatidylcholine are exposed to the vascular compartment [11]. When cells are stimulated, the asymmetric distribution of phospholipids is disturbed resulting in the externalization of PS on the outer leaflet. Furthermore,MPs have been found to express tissue factor (TF), and thus to provide an environment favourable to initiation and support of coagulation [12,13].