Beyond Platelet Counts: Assessing Safety of Post-Splenectomy TPO-RA Use in ITP

Immune thrombocytopenia (ITP) carries an increased risk of thrombosis, which may be further amplified by splenectomy and thrombopoietin receptor agonists (TPO-RAs). While each intervention has been individually studied for its thrombotic risk, data are lacking on the safety of post-splenectomy TPO-RA use. We conducted a retrospective cohort study of adult ITP patients who underwent splenectomy between 2011 and 2024. Patients were stratified based on post-splenectomy TPO-RA use. The primary outcome was incidence of thrombosis. Secondary outcomes included bleeding, mortality, and hematologic response. Time-to-event analyses and multivariate Cox regression were performed. Among 88 patients, 37 (42%) patients received TPO-RA post-splenectomy. Thrombosis occurred in 17 patients in the TPO-RA group versus 14 patients in the non-TPO-RA group (p=0.07). The 10-year cumulative incidence of thrombosis was numerically higher in the TPO-RA group (57% vs. 36%), with clustering of events within the three months of post-splenectomy TPO-RA initiation. Venous events predominated; arterial events were rare. No significant differences were observed in bleeding or mortality rates between groups. Platelet counts alone did not independently affect bleeding or thrombosis. TPO-RA use after splenectomy was not significantly associated with increased thrombosis risk; however, early initiation may coincide with a high-risk period, and the sustained numerical difference in cumulative incidence throughout follow-up highlights potential clinical relevance. These findings support the need for individualized thromboprophylaxis and prospective evaluation of TPO-RA safety in this setting.