Thrombopoiesis

Thrombopoiesis is the process by which platelets are produced, primarily in the bone marrow from megakaryocytes. It begins with hematopoietic stem cells differentiating along the megakaryocyte lineage into megakaryoblasts, which mature into polyploid megakaryocytes through endomitosis. The mature megakaryocyte enlarges and accumulates cytoplasm. In the marrow, these cells extend long cytoplasmic processes, called proplatelets, into the sinusoidal blood vessels. Shear forces and fragmentation within the lumen release platelets from the proplatelets into the circulation. The majority of thrombopoiesis occurs in the marrow; some data suggest extramedullary sites such as the lung may contribute a minority of platelets in mammals.

Regulation is dominated by thrombopoietin (TPO), a glycoprotein produced mainly by the liver. TPO binds to the c-Mpl receptor on megakaryocytes and platelets, stimulating proliferation, maturation and platelet production. Platelets themselves express the receptor, creating a feedback loop that links platelet mass to TPO availability: higher platelet counts remove more TPO from circulation, reducing production; conditions that reduce platelet counts increase TPO levels and drive thrombopoiesis.

Clinical relevance: impaired thrombopoiesis underlies various thrombocytopenias, including inherited amegakaryocytic thrombocytopenia and acquired conditions, as well as some myeloproliferative disorders. Therapies often target the TPO–c-Mpl axis or megakaryocyte maturation to restore platelet production.