Schematic of current concepts of platelet production showing mature megakaryocytes localized close to bone marrow sinusoids. (A) Proplatelet model. Megakaryocytes polarize their demarcation membrane system (DMS) as prerequisite for directed release of long cytoplasmic protrusions called proplatelets, which are driven by reorganization of microtubules (shown in green) into the sinusoidal lumen. Platelet intermediates (preplatelets) and platelets are shed into the circulation by blood shear forces. The terminal stage of platelet production occurs in the bloodstream. (B) Membrane budding model. Continuous release of final platelets directly from the megakaryocyte via membrane budding. (C) Thin-section electron micrograph showing the hallmark features of blood platelets. Resting platelets have a discoid shape with clear α-granules (i), microtubules (ii), and dense granules (iii). (D) Electron micrograph showing a megakaryocyte membrane bud. Reproduced from Potts et al⁹ (© 2020 Potts et al) under a CC BY-NC-SA 4.0 license. (E) Electron micrograph showing a bleb from a cultured mouse megakaryocyte that lacks the characteristic features of an assembling platelet. Scale bar, 1 μm. Cells were fixed, processed, and imaged as previously described.¹⁰