Evaluating the Potentially Toxic Effects of Thrombopoietin Receptor Agonist (Eltrombopag) in Immune Thrombocytopenic Pediatric Patients and Animal Models

ABSTRACT Eltrombopag is currently approved and efficacious for treating children's immune thrombocytopenia (ITP). Eltrombopag poses a risk of severe liver damage and renal impairment. This study aimed to evaluate the potential toxic impacts and assess the hepatic and renal dysfunctions using early predictors in pediatric ITP patients with eltrombopag. Additionally, to confirm the existence of these harmful effects, toxicities in rats treated with eltrombopag were investigated. According to the treatment observation period, four groups were established: baseline, 1, 3, and 6 months after treatment groups. Fifty pediatric ITP patients were analyzed for demographic characteristics and different laboratory parameters. Hepatic and renal morphological alterations were evaluated in rats at various intervals of eltrombopag treatment. The patients were 22 males and 28 females aged 2–18 years. Eltrombopag caused hepatic and renal dysfunctions, manifested as significantly elevated levels of ALT, AST, ALP, GGT, TSB, urea, and creatinine after 3 months on treatment, whereas elevated LDH, cystatin C, and NGAL after 1 month on treatment increased their elevations before other parameters ( p ‐value = 0.001). Most patients were distinguished in Grades 1 and 2 of liver and renal injuries, with only some cases as Grade 3. Rat tissues were affected after eltrombopag treatment. Pediatric patients receiving eltrombopag may develop liver and renal dysfunctions. Patients should be regularly monitored to allow immediate intervention and reduce the possibility of therapy failure. To our knowledge, this is the first study that used early predictors to detect hepatic and renal injuries in pediatric ITP patients with eltrombopag.