Trombotsütopeiin

Trombotsütopeiin, or thrombopoietin (TPO), is a glycoprotein hormone that regulates platelet production. It is produced mainly by the liver, with smaller contributions from the kidney and bone marrow stromal cells. TPO acts as a key driver of megakaryopoiesis, the process by which megakaryocytes mature and release platelets into the bloodstream.

Mechanism and signaling: TPO binds to the MPL receptor (CD110) on hematopoietic stem cells and megakaryocyte progenitors. This engagement activates signaling pathways including JAK-STAT, MAPK, and PI3K, promoting proliferation and maturation of megakaryocytes and increasing platelet output.

Regulation: Circulating TPO levels are largely controlled by the platelet mass. Platelets and megakaryocytes express MPL receptors and clear TPO from circulation; thus, a low platelet count raises available TPO, stimulating production, while a high platelet count lowers it. Inflammatory signals, particularly interleukin-6, can also enhance hepatic TPO production.

Clinical relevance: Defects in the THPO gene or in the MPL receptor can cause inherited thrombocytopenia. Therapeutically, thrombopoietin receptor agonists such as romiplostim and eltrombopag are used to treat immune thrombocytopenia and other chronic thrombocytopenias by stimulating megakaryopoiesis. Historical use of recombinant TPO has largely been supplanted by these receptor agonists due to immunogenicity and safety concerns. Side effects may include marrow changes and, in some settings, an altered risk of clonal evolution, requiring careful monitoring.

See also: megakaryopoiesis, MPL receptor, JAK-STAT signaling, thrombocytopenia.