Thrombotic events associated with thrombopoietin receptor agonists in children with immune thrombocytopenia: A safety analysis of clinical studies and FDA pharmacovigilance database.

Authors

Jiaojiao Zhao, Die Han, Yuezi Huang, Shuimei Sun, Junjie Lan, Rui Zhang, Huaye Zhao, Linfang Hu, Jiaxue Wang, Wenyi Zheng, Rui He, Jiaxing Zhang

Published in

Journal of thrombosis and thrombolysis. Oct 25, 2026. Epub Oct 25, 2026.

Abstract

The thrombotic risk of thrombopoietin receptor agonists (TPO-RAs) in pediatric immune thrombocytopenia (ITP) is unclear. We systematically evaluated this risk using integrated clinical, real-world, and pharmacovigilance evidence. We searched PubMed, Embase, Cochrane Library, CNKI, VIP Database, and Wanfang Data for randomized controlled trials (RCTs) and observational studies (search cutoff: March 10, 2025), with meta-analysis performed to quantify thrombotic incidence. A retrospective pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) was conducted, extracting TPO-RAs-associated thrombotic cases (Q1 2004 ~ Q3 2025); disproportionality was assessed using reporting odds ratio (ROR) and information component (IC). This study is registered with Prospective Register of Systematic Reviews (PROSPERO) (CRD42024534405). A total of 6 RCTs (336 patients) and 16 single-arm real-world studies (965 patients) were included in the meta-analysis. No thrombotic events were reported in RCTs. Meta-analysis of single-arm studies revealed an extremely low pooled incidence of thrombotic events (0.21%, 95% confidence interval [CI]: 0.025% ~ 0.74%). Pharmacovigilance analysis of FAERS identified 41 TPO-RAs-associated thrombotic cases, with no overall significant signal of increased thrombotic risk (ROR = 0.67, 95% CI: 0.40 ~ 1.10; IC = -0.22, 95% CI: -0.84 ~ 0.36). However, subgroup analysis by individual TPO-RAs demonstrated significant thrombotic safety signals for eltrombopag (n = 25; ROR = 2.03, 95% CI: 1.37 ~ 3.01; IC = 1.01, 95% CI: 0.39 ~ 1.52) and avatrombopag (n = 5; ROR = 12.6, 95% CI: 4.71 ~ 33.73; IC = 3.34, 95% CI: 0.66 ~ 3.31). Among the 41 cases with available outcome data, 4 (9.76%) were fatal, with fatal rates varying by agent: eltrombopag (4.20%), romiplostim (18.20%), and avatrombopag (25.00%). TPO-RAs are associated with an extremely low incidence of thrombotic events in pediatric patients with ITP, with no definitive causal relationship established and no overall significant thrombotic safety signal detected in FAERS. These findings support the continued use of TPO-RAs in this population. Nevertheless, vigilant thrombotic risk monitoring is warranted-particularly in patients receiving eltrombopag or avatrombopag, as well as those with underlying prothrombotic risk factors-to optimize clinical safety in this vulnerable population.

PMID:
42927567
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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