Formation of procoagulant microparticles and properties

Abstract

The platelet procoagulant response consists of providing a catalytic surface where vitamin K-dependent clotting factors can interact with cofactors to form the characteristic enzyme complexes of the cascade culminating in the generation of sufficient thrombin for effective hemostasis. The essential element allowing such a local concentration is the anionic aminophospholipid phosphatidylserine, sequestered in the inner leaflet of the plasma membrane of resting cells but swiftly translocated to the outer leaflet after stimulation. Phosphatidylserine egress is followed by the shedding of membrane fragments, the so-called microparticles or microvesicles, also endowed with procoagulant properties more particularly when they harbor tissue factor, the major initiator of blood coagulation reactions. Furthermore, because microparticles hijack a number of membrane and cytoplasmic components from the cells they derive, they can elicit various responses in proximal or remote cells they interact with and can therefore be viewed as intercellular "macromessengers". Although several regulatory mechanisms have been proposed, the main actors responsible for the whole process of phosphatidylserine transmembrane redistribution and subsequent microparticle release remain to be identified.