trombopoëtine

Trombopoëtine, also known as thrombopoietin (TPO), is a cytokine that regulates thrombopoiesis, the production of platelets. It is produced mainly by the liver, particularly by hepatic sinusoidal endothelial cells and hepatocytes, with minor contributions from the kidney and other tissues. TPO acts by binding to the MPL receptor on the surface of megakaryocyte progenitors in the bone marrow, stimulating their proliferation and maturation and thereby promoting platelet production. The signaling involves pathways such as JAK-STAT, which drive megakaryocyte growth and platelet release.

Plasma TPO levels are tightly regulated by platelet mass. Circulating platelets and megakaryocytes express the MPL receptor and clear TPO from circulation; as platelet counts rise, TPO clearance increases and its plasma level falls. Conversely, low platelet mass leads to higher circulating TPO, which stimulates thrombopoiesis. This feedback mechanism helps maintain stable platelet numbers under normal conditions.

Clinical relevance: Abnormalities of the TPO/MPL axis can contribute to platelet disorders, including thrombocytopenia and thrombocytosis. Therapeutically, TPO receptor agonists such as romiplostim and eltrombopag are used to treat certain forms of thrombocytopenia, notably chronic immune thrombocytopenia. These agents stimulate the MPL receptor to increase platelet production, but their use can be associated with adverse effects, including risks of marrow changes, thrombotic events, or liver toxicity depending on the agent and context.