Eltrombopag-Induced Myelofibrosis in Patients with Adult Immune Thrombocytopenia: Scoping Review

Abstract

Immune thrombocytopenic purpura is a clinical syndrome of thrombocytopenia that manifests as a bleeding tendency, typical skin rashes, easy bruising, or extravasation of blood from the capillaries. Defects in the thrombopoietin-receptor (TPOR)/myeloproliferative leukaemia virus/JAK2 axis leads to haematological diseases such as thrombocytopenia or pancytopenia through the inhibition of the megakaryopoiesis process. Thrombopoietin-receptor agonists (TPORA), such as eltrombopag, increase platelet count by stimulating the TPOR. Bone marrow (BM) fibrosis has been reported in patients receiving TPORA. Myelofibrosis (MF) may be induced by mutations in JAK2, CALR, and MPL genes. This review gives an insight on MF as a serious side effect induced by eltrombopag. This review enriches the evidence of MF induced by eltrombopag after long-term administration ranging from 6 months to 7 years. MF is mostly spontaneous and decreases after discontinuation of medication; however, in a few cases it becomes persistent. This major issue should be treated with high concern. The authors recommend that any patient on eltrombopag treatment should be under vigilant observation and closely monitored for any sign of MF by clinical manifestation and any abnormal result from peripheral blood smear examination, and should additionally undergo BM biopsy for confirmation and detection of the severity of MF. The authors recommend discontinuing the medication if this side effect occurs. The authors also recommend to conduct larger studies for longer periods using serial BM before, and periodically after, eltrombopag treatment to evaluate the characteristics of this adverse effect.