Platelet biology and etiopathogenesis of congenital platelet disorders

Platelets are small anucleate blood cells derived from megakaryocytes, essential for hemostasis and involved in thrombosis, inflammation, immunity, and tissue repair. Their production depends on tightly regulated processes of megakaryopoiesis and thrombopoiesis. Inherited platelet disorders (IPDs) are a heterogeneous group of rare diseases caused by germline variants affecting megakaryocyte development and maturation, platelet production, structure, or function. These include inherited thrombocytopenias, characterized by reduced platelet counts, and inherited platelet function disorders, caused by qualitative platelet defects. Depending on the underlying genetic alteration, patients may present with bleeding, syndromic manifestations, or predisposition to hematologic malignancies. Recent advances in platelet biology and molecular genetics have improved diagnosis, personalized management, and genetic counseling. In parallel, IPDs have emerged as valuable human models for understanding the molecular mechanisms regulating platelet biogenesis and function in health and disease.