Platelet production is primarily regulated by the thrombopoietic cytokine thrombopoietin (TPO). In most cases thrombopoietin serum levels are determined by the rate of c-mpl receptor-mediated degradation after TPO uptake into platelets and megakaryocytes. The contribution of increased TPO protein synthesis by a translational mechanism was recently appreciated as the cause for hereditary thrombocythemia and will have to be elucidated in other conditions of thrombocytosis in association with increased TPO levels.
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