Eltrombopag (EPAG), a thrombopoietin receptor agonist, has emerged as a valuable option for the treatment of immune thrombocytopenic purpura. However, its use has raised concerns regarding thrombotic complications. Herein, we present a case involving a 60-year-old woman with immune thrombocytopenic purpura and underlying antiphospholipid antibody syndrome who developed abdominal pain and acute kidney injury shortly after initiating EPAG therapy. Kidney histopathology revealed thrombi in the afferent glomerular arterioles, suggesting a link between EPAG and thrombotic events. Despite EPAG discontinuation, the patient's kidney function deteriorated, necessitating hemodialysis. As an additional treatment, plasma exchange (PE) was performed to remove EPAG. High-performance liquid chromatography analysis showed a reduction in the EPAG concentration after PE, indicating partial removal. The patient's kidney function gradually improved, and hemodialysis was successfully discontinued. The findings from this case suggest that thrombotic complications should be considered when administering EPAG to patients with antiphospholipid antibody syndrome. PE may be a useful treatment option if thrombosis is induced by EPAG.