Thrombotic risk with thrombopoietin receptor agonists in immune thrombocytopenia: Real-world evidence from a multicenter Japanese study.

Abstract Background: Thrombopoietin receptor agonists (TPO-RAs), which are widely used as second-line or later treatments for immune thrombocytopenia (ITP), have significantly transformed ITP management. However, their association with thrombotic events remains controversial, particularly in patients with a pre-existing thrombotic risk. To our knowledge, this is one of the largest Asian real-world studies addressing thrombotic risk factors for ITP during the TPO-RA era. We aimed to identify risk factors for thrombosis in patients newly diagnosed with ITP in Japan. Methods: We retrospectively analyzed 687 eligible patients diagnosed with primary ITP between 2011 and 2020 across 20 centers in the Hokkaido Hematology Study Group. Clinical data included thrombosis history, cardiovascular risk factors, treatment responses, antiphospholipid antibody (aPL) status, and subsequent thrombotic events. Multivariate Cox regression analysis was used to identify independent risk factors. Results: Of the 687 patients, 247 (36.0%) received TPO-RAs. Thrombotic events occurred in 31 patients (4.5%), including 15 (6.1%) in the TPO-RA group. Multivariate analysis revealed aPL positivity (HR 5.31, 95% CI 1.07–26.4, p=0.042) and prior thrombosis (HR 7.10, 95% CI 2.93–17.2, p<0.001) as independent risk factors. Among TPO-RA-treated patients, the cumulative thrombosis incidence was significantly higher in those with a thrombotic history (p=0.00081) and tended to be higher with aPL positivity (p=0.057), while no association was observed in untreated patients (p=0.35). Conclusion: TPO-RA therapy may increase thrombotic risk in ITP patients with aPL positivity or prior thrombosis. Risk stratification and careful monitoring are essential when initiating TPO-RA in high-risk populations.