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Tpo mimetics romiplostim and eltrombopag stimulate megakaryocytopoiesis by mechanisms similar to those respondible for hereditary thrombocytosis.In particular, eltrombopag, a nonpeptide Tpo mimetic, binds to MPL in its transmembrane region and directly activates the signal transduction pathway. Thus, chronic eltrombopag administration reminds the constitutive activation of MPL as observed in patients with MPL germline muatations. Since these patients usually develop with aging bone marrow fibrosis, and given that these drugs have to be lifelong administered, concern emerged when it was noticed that some patients with immune thrombocytopenia (ITP) receiving romiplostin developed bone marrow fibrosis

Thrombopoietin Receptor Activation, Thrombopoietin Mimetic Drugs, and Hereditary Thrombocytosis: Remarks on Bone Marrow Fibrosis