Trombopoiesis

Trombopoiesis is the process by which platelets are produced in the bone marrow from hematopoietic stem cells. It begins with differentiation of stem cells into the megakaryocyte lineage, passing through megakaryocyte-erythroid progenitors, megakaryoblasts, and promegakaryocytes, then culminating in mature megakaryocytes. These cells undergo endomitosis, an incomplete mitosis that increases their DNA content and polyploidy, enabling substantial cytoplasm to support platelet production.

Mature megakaryocytes extend long cytoplasmic processes called proplatelets into bone marrow sinusoids. Fragmentation of the demarcation membrane system and cytoplasmic remodeling releases platelets, which enter the bloodstream. Platelet shedding is driven by cytoskeletal dynamics, particularly microtubules, and ends with the release of anucleate platelets into circulation.

Thrombopoiesis is primarily regulated by thrombopoietin (TPO), a cytokine mainly produced by the liver and, to a lesser extent, the kidney. TPO binds the c-MPL receptor on megakaryocytes and platelets, activating signaling pathways such as JAK-STAT to promote proliferation, maturation, and platelet production. Platelet mass regulates circulating TPO levels through receptor-mediated clearance; low platelet counts increase TPO availability and stimulate thrombopoiesis, while high counts promote clearance and reduce production. Additional supportive factors include interleukins such as IL-3, IL-6, and IL-11.

Most thrombopoiesis occurs in the bone marrow, with extramedullary sites like the liver or spleen contributing under stress. Platelets circulate for about 7–10 days before clearance by the spleen and liver. Clinically, thrombopoiesis can be enhanced with thrombopoietin receptor agonists in conditions such as immune thrombocytopenia.