Clinical Pathology: Hematology & Coagulation, Transfusion Medicine

• Thrombopoietin (TPO) stimulates megakaryocyte proliferation and differentiation, as well as platelet production.

• TPO is the ligand for CD110, the TPO receptor. The c-mpl gene encodes the CD110 protein.

• After binding TPO, CD110 forms dimers, leading to phosphorylation and activation of CD110, Janus kinases (JAKs), signal transducers and activators of transcription (STATs), and other downstream pathways, including mitogen-activated protein (MAP) kinases.

• Liver parenchymal and endothelial cells, as well as bone marrow stromal cells, are the main sites of TPO production.

• A recombinant form of TPO was used as a pharmaceutical, but trials were stopped when study volunteers developed anti-TPO autoantibodies and subsequent thrombocytopenia.

• Current TPO mimetics stimulate the TPO receptor but are not structurally related to TPO. Therefore, autoantibodies recognizing TPO are not a long-term complication.

• However, the TPO mimetics have long-term side effects of thromboembolism, hepatic toxicity, and bone marrow reticulin deposition.

• TPO mimetics are used as a second-line treatment for chronic immune thrombocytopenia when there is a risk of bleeding.



 
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