(A) A model for megakaryocytopoiesis demonstrates the progressive increase in size as megakaryocytes mature in the marrow, with mature megakaryocytes developing cytoplasmic projections called proplatelets. Platelet release occurs from the ends of proplatelet projections, with at least some platelet release occurring directly in the marrow circulation from proplatelet projections that extrude through the marrow’s fenestrated vasculature. (B) Fuentes et al. (19) have demonstrated that infused mature megakaryocytes release platelets into the circulation, thereby increasing circulating platelet counts, and that these platelets contribute to hemostasis at the site of vascular injury.