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Biology and physiology of thrombopoietin

David J Kuter, MD, DPhil
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Thrombopoietin (TPO) is the physiologically relevant regulator of platelet production. Although the concept of a platelet growth factor analogous to erythropoietin had been proposed in the 1950s, it was not until 1994 that the existence of this hematopoietic growth factor was demonstrated and the protein purified [1-5]. Although historically called "thrombopoietin" [6], its discoverers also called it by several other names, including megapoietin [3], megakaryocyte growth and development factor (MGDF) [4], and c-Mpl ligand [2]. The last name is often used instead of TPO because the receptor for TPO, called c-Mpl, was discovered prior to the identification of TPO [7] and was instrumental in helping to purify the ligand (ie, the c-Mpl ligand) that bound to it.

This topic will review the biology and physiology of TPO. The potential clinical applications of TPO, ranging from the management of thrombocytopenic states to improving yields from platelet apheresis, are discussed separately [8]. (See "Clinical applications of thrombopoietic growth factors".)


TPO is produced primarily in liver parenchymal cells with much smaller amounts being made in the kidney and bone marrow [9,10]. It is synthesized as a 353 amino acid precursor protein with a molecular weight of 36 kDa [2,4,11]. Following the removal of the 21 amino acid signal peptide, the remaining 332 amino acids undergo glycosylation to produce a 95 kDa glycoprotein (figure 1). The glycoprotein is then released into the circulation with no apparent intracellular storage in the liver or kidney.

TPO is an unusual hematopoietic growth factor in a number of ways:

It is much larger than most other regulators of blood cell production such as G-CSF (granulocyte colony-stimulating factor) and erythropoietin.

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Literature review current through: Nov 2017. | This topic last updated: Nov 14, 2017.
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