{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T04:16:32Z","timestamp":1792988192817,"version":"4.5.0"},"reference-count":39,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"unspecified","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,7,22]]},"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Thrombopoietin receptor agonists (TPO-RAs) are widely used in thrombocytopenia, yet their association with thromboembolic events (TEEs) remains concerning. This study aimed to assess the real-world TEE risk associated with TPO-RAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Retrospective pharmacovigilance analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Both FAERS and JADER were searched from January 2004 to March 2025.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>Disproportionality analyses were performed using reporting OR (ROR), proportional reporting ratio (PRR), informational component (IC) and empirical Bayesian geometric mean (EBGM) to identify potential safety signals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>4005 TEE from FAERS and 569 from JADER were analysed. Venous TEE showed higher prevalence and signal intensity (FAERS: n=1489, ROR 4.19, PRR 4.14, EBGM05 3.94, IC025 0.37; JADER: n=269, ROR 15.95, PRR 14.27, EBGM05 12.56, IC025 2.14). Lusutrombopag had the strongest TEE signal (FAERS: n=7, ROR 8.80, PRR 7.77, EBGM05 4.00, IC025 1.25; JADER: n=41, ROR 38.02, PRR 16.94, EBGM05 11.45, IC025 2.38). FAERS identified 49 positive signals, while JADER identified 30, with 20 signals overlapping. Subgroup analysis indicated males had higher arterial TEE risk with TPO-RAs, while females had higher venous TEE risk in both FAERS and JADER. In FAERS, elderly (\u226560 years) showed elevated arterial TEE risk with TPO-RAs and romiplostim, while non-elderly had higher venous TEE risk with avatrombopag and eltrombopag.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study provided real-world evidence of TEE associated with TPO-RAs, highlighting a strong link despite variations in signal values and regional reporting practices. Findings underscore ongoing clinical safety surveillance for TPO-RAs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-099153","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T02:37:10Z","timestamp":1754879830000},"page":"e099153","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Relationship between thromboembolic events and thrombopoietin receptor agonists: a pharmacovigilance analysis of the FDA Adverse Event Reporting System and the Japanese Adverse Drug Event Report"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8954-5405","authenticated-orcid":false,"given":"Xiaojia","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhang","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Xiamen Chang Gung Hospital Hua Qiao University, Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,8,10]]},"reference":[{"key":"2025123106461179000_15.8.e099153.1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.212845"},{"key":"2025123106461179000_15.8.e099153.2","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25042163","article-title":"Current Understanding of Immune Thrombocytopenia: A Review of Pathogenesis and Treatment Options","volume":"25","author":"Mititelu","year":"2024","journal-title":"Int J Mol Sci"},{"key":"2025123106461179000_15.8.e099153.3","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1055\/a-2247-4209","article-title":"Update on the Use of Thrombopoietin-Receptor Agonists in Pediatrics","volume":"44","author":"Gebetsberger","year":"2024","journal-title":"Hamostaseologie"},{"key":"2025123106461179000_15.8.e099153.4","doi-asserted-by":"crossref","unstructured":"Stafylidis C , Vlachopoulou D , Syriopoulou S , et al . 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