The study reveals an age-progressive platelet differentiation pathway from hematopoietic stem cells (HSCs) that causes thrombocytosis and increased thrombosis in aged mice. This pathway bypasses the canonical progenitor cascade and directly generates megakaryocyte progenitors (MKPs) that produce platelets. The aging-induced MKPs are transcriptionally distinct from canonical MKPs and exhibit enhanced expansion, clonal potential, and platelet reconstitution capacity. These age-enriched MKPs also show increased platelet hyper-reactivity, contributing to exacerbated clot formation and thrombosis in response to vascular injury. The findings highlight a novel mechanism of platelet dysregulation in aging, which may contribute to cardiovascular disorders in the elderly.The study reveals an age-progressive platelet differentiation pathway from hematopoietic stem cells (HSCs) that causes thrombocytosis and increased thrombosis in aged mice. This pathway bypasses the canonical progenitor cascade and directly generates megakaryocyte progenitors (MKPs) that produce platelets. The aging-induced MKPs are transcriptionally distinct from canonical MKPs and exhibit enhanced expansion, clonal potential, and platelet reconstitution capacity. These age-enriched MKPs also show increased platelet hyper-reactivity, contributing to exacerbated clot formation and thrombosis in response to vascular injury. The findings highlight a novel mechanism of platelet dysregulation in aging, which may contribute to cardiovascular disorders in the elderly.