Platelet Subpopulations in Health and Disease: Heterogeneity, Clinical Associations, and Therapeutic Targeting

Platelets are often described in simple terms as small anucleate cells that mediate hemostasis, but studies over more than half a century have shown that circulating platelets are heterogeneous in size, density, age, and functional responses. These subtypes not only contribute to normal hemostasis but also play pivotal roles in the pathogenesis of diverse diseases, including cardiovascular, inflammatory, and malignant disorders. Accumulating evidence indicates that alterations in specific platelet subtypes are closely linked to disease onset, progression, and severity, underscoring their importance as both biomarkers and potential therapeutic targets. Current clinical assessments of platelet status rely primarily on platelet count and mean platelet volume (MPV) as part of routine complete blood count analysis. However, these global measures often fail to capture differences in platelet subtypes, which may remain undetected despite their significant contribution to disease pathology. This gap highlights the necessity of moving beyond conventional metrics toward a more nuanced understanding of platelet heterogeneity and its clinical implications. In this review, we discuss the diversity of platelet subpopulations and their roles in health and disease, emphasizing how specific subsets contribute to divergent pathological mechanisms. We also highlight emerging strategies that target defined platelet subpopulations, illustrating how this knowledge could pave the way for more precise diagnostic and therapeutic approaches.