Phosphatidylserine-positive REVS potentiate thrombin generation [122], [123] and [125] through factor XI activation [28], [122] and [126]. However, other investigators identified activated factor XII as being the key player in the coagulation cascade [127]. In paroxysmal nocturnal hemoglobinuria, complement activation may be involved in EVS generation which contributes

to the thrombotic profile of these patients [21], [128], [129] and [130]. In stem cell transplants, REVS may be useful in distinguishing acute graft-versus-host disease from infection or sepsis [131]. However, other types of EVS are elevated in such patients [132] and [133]. In malaria, rates of REVS are also correlated with the degree of parasitemia and the severity of Ruxolitinib clinical trial the infection [133] and [134]. During RBC storage, many biochemical changes happen, referred as “storage lesions” including RBCS membrane modifications (it becomes more rigid), lipid rafts rearrangement, disruption of phospholipids asymmetry and EVS release [4], [71] and [135]. The accumulation of EVS during blood storage is well described [74]. Recently, we identified that these EVS have factor XI dependent procoagulant properties and that they are able to initiate and propagate thrombin generation

[28]. EVS from stored RBCS also carry blood group antigens that may play a role in alloimmunization [41]. Ipilimumab in vitro Platelet production is a complex process [136], beginning within the bone marrow. Different molecular mechanisms are involved in the formation of platelets from megakaryocytes [137], leading to the splitting of large platelets which can also be considered as megaparticles. Platelets in circulation release both large vesicles that are plasma membrane-derived microparticles and small ones that represent multivesicular body-derived EXS [138]. The distinction between these two populations of PEVS is difficult because of an overlap in their molecular properties and in their sizes. Furthermore, as PEVS are released through several induction pathways,

different types of PEVS may be produced, each one bearing its mechanism of action. Methisazone In a paper dealing with the biology of PEVS, Varon et al. reviewed the extra-hemostatic effects of PEVS and presented the possible roles of PEVS other than participation in blood coagulation [139]. In summary, they showed that PEVS express and transfer functional receptors from platelet membranes, increase expression of adhesion molecules on cells, stimulate the release of cytokines, activate intracellular signaling pathways, alter vascular reactivity, induce angiogenesis, and are involved in cancer metastasis. They also mentioned that a high PEVS level is highly correlated with aggressive tumors and a poor clinical outcome. PEVS also have important physiopathological role in patients presenting with type-II heparin induced thrombocytopenia [140].