Model of platelet maturation in the bloodstream. (A) Circulating platelets are heterogeneous in size and age. Immature platelets >3 μm in diameter are termed preplatelets (identified by green cytoplasm). These platelet progenitor cells mature by continuously transforming into barbell platelets and undergoing fission into 2 smaller platelets until reaching a size threshold of <3 μm in diameter. Under steady-state production, not all large platelets are immature. Unlike preplatelets, these lack the capacity to undergo maturation. Therefore, mature platelets consist of small and large platelets (identified by gray cytoplasm). (B) Barbell platelets originate from immature preplatelets consisting of a greater nucleic acid content, granule content, number of mitochondria, and HLA I expression, compared with mature small platelets. In contrast, mature large platelets contain a similar number of granules and mitochondria, which are nonspecifically labeled with dyes used for measuring IPF and RPs. Large, mature platelets express slightly less HLA I than immature preplatelets, which could separate preplatelets from mature, large platelets.