Extracellular vesicles in vascular pathophysiology 1 Currently, the topic of extracellular vesicles (EVs) and their involvement in disease promotion and progression is gaining important insight in diagnostics and treatment. 5 In this review, we focus on specific EV characteristics, still not intensively investigated, which contribute to the biological activity of EVs, that is, composition of the EV surface called a corona, and its charge.The biological activity of EVs depends on their cargo and their biological availability and biostability. The estimated blood plasma concentration of EVs in healthy individuals is between 10 8 and 10 14 EVs/ml. Such discrepancies, more than 6 orders of magnitude, depend mainly on the isolation protocol and possible contamination by other colloidal particles present in the plasma, such as lipoproteins and large protein aggregates. 6 In total platelet poor plasma, the average platelet microvesicle (PMV) content has been estimated at 10 9 to 10 10 EVs/ml in patients on antiplatelet drugs and healthy individuals. PMV abundance depends mainly on the plasma purity and preanalytical handling. 7-11 Assuming that one -third of the plasma EVs is of platelet origin, the number of the plasma EVs can be approximately 10 10 EVs/ml. 6 The average plasma residence time of intravenously delivered EVs ranges from 30 to 80 minutes and it is mainly regulated by the phagocyting activity of the mononuclear phagocyte system and by Introduction When about 50 years ago Wolf 1 noticed that some tiny and highly abundant objects present in human blood plasma contribute to clotting events, it seemed that there is something beyond clotting factors that may support platelets / thrombocytes in their aggregation and formation of a thrombus. This coagulant particulate material released from platelets (referred to as "platelet dust") was produced in considerably larger amounts than required for thrombin generation. It was detected not only in plasma but also in serum, and its presence seemed to be associated with the platelet -like activity of the serum. 1 The platelet activation leads to secretion of granules containing the procoagulant material and proteins involved in cytoskeletal arrangement, synaptic transportation, and secretion from their internal space. 2 The processes of the formation and secretion of platelet "particles" are analogous to the processes occurring in other cells, including endothelial cells. They result in the formation of 2 types of membrane vesicles: bigger ones shed from the surface and named microvesicles (ectosomes) of 100 nm to 1 µm in diameter, and exosomes, measuring 40 nm to 100 nm in diameter. The latter are similar in size to the internal vesicles in multivesicular bodies (MVBs) and α -granules, 3,4 and can be compared to endothelial vesiculation (FIguRE 1).