[BINDING OF CELL-DERIVED MICROPARTICLES WITH FIBRIN IN BLOOD CLOTTING]

Direct effects of circulating blood microparticles on fibrin formation and structure were studied. Clots made from platelet-free plasma and from microparticle-depleted plasma obtained by filtration was studied in parallel, including clots from the microparticle-depleted plasma replenished with phospholipids. Fibrin formation was induced by exogenous thrombin without Ca2+ to prevent formation of endogenous thrombin and exclude indirect kinetic effects of microparticles related to thrombin generation. In the presence of natural microparticles or exogenous phospholipids the maximal turbidity of fibrin clots was significantly smaller, indicating structural distinctions from the clots formed in the absence of microparticles. Scanning electron microscopy and confocal microscopy showed that clots formed from platelet-free plasma, i. e. in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contained 0.1-0.5-μm-large CD61-positive granules associated with fibrin fibers that were identical to the particles found on the surface of filters used for microparticle removal. The results show that platelet-derived microparticles bind to fibrin and affect its structure. The revealed interactions of cell-derived microparticles with fibrin highlight a previously unknown role of microparticles in hemostasis and thrombosis as constituents and modulators of a fibrin clot structure.