The pathobiology of platelet and megakaryocyte extracellular vesicles: A (c)lot has changed.

Platelet-derived extracellular vesicles (PEVs) were originally studied for their potential as regulators of coagulation, a function redundant with that of their parent cells. However, as the understanding of the diverse roles of platelets in hemostasis and disease has developed, so has the understanding of PEVs. In addition, the more recent revelation of constitutively released megakaryocyte-derived extracellular vesicles (MKEVs) in circulation provides an interesting counterpoint and avenue for investigation. In this review, we highlight the historical link of PEVs to thrombosis and hemostasis and provide critical updates. We also expand our discussion to encompass the roles that distinguish PEVs and MKEVs from their parent cells. Furthermore, the role of extracellular vesicles in disease pathology, both as biomarkers and as exacerbators, has been of great interest in recent years. We highlight some of the key roles that PEVs and MKEVs play in autoimmune blood cell disorders, liver pathology, and cardiovascular disease. We then look at the future of PEVs and MKEVs as candidates for novel therapeutics.