{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T11:59:50Z","timestamp":1781697590915,"version":"3.54.5"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Reports"],"abstract":"<jats:p>Thrombopoietin receptor agonists (TPO-RAs) have become central second-line treatments for children with persistent or chronic immune thrombocytopenia (ITP). Their efficacy has encouraged broad use, but difficult-to-treat patients who respond suboptimally may be exposed to repeated agent switching, prolonged treatment, or doses exceeding approved limits. This commentary uses a focused narrative approach to address whether the risk of treatment-associated marrow fibrosis should be interpreted primarily as a consequence of treatment duration or as a risk marker linked to supraphysiological treatment intensity in non-responders. A recent Haematologica report by Ma and colleagues identified clinically significant bone marrow myelofibrosis in a highly selected cohort of children with chronic ITP undergoing marrow re-evaluation after suboptimal response or loss of efficacy during TPO-RA therapy. The most relevant message is not simply that fibrosis can occur, but that it was independently associated with treatment intensification, particularly overdose and frequent switching. The biological plausibility of this association is supported by the known capacity of sustained megakaryocytic stimulation to promote local pro-fibrotic signaling and reticulin deposition. This commentary places this safety concern in the context of pediatric ITP epidemiology, current regulatory indications, expert approaches to refractory disease, and practical surveillance considerations. TPO-RAs should not be viewed as routine treatment for newly diagnosed pediatric ITP; their principal role remains in selected children with persistent or chronic disease who require second-line therapy. Failure to respond at the maximum approved dose should prompt diagnostic and therapeutic reassessment rather than automatic treatment escalation. The emerging lesson is that response-adapted therapy must also be risk-adapted therapy.<\/jats:p>","DOI":"10.3390\/pediatric18030082","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T10:19:53Z","timestamp":1781691593000},"page":"82","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["When Platelet Stimulation Becomes Marrow Stress: Rethinking Thrombopoietin Receptor Agonist Intensification in Pediatric Immune Thrombocytopenia"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-6671","authenticated-orcid":false,"given":"Maurizio","family":"Aric\u00f2","sequence":"first","affiliation":[{"name":"Interdisciplinary Department of Medicine, University of Bari Aldo Moro, 70121 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1182\/bloodadvances.2019000812","article-title":"Updated international consensus report on the investigation and management of primary immune thrombocytopenia","volume":"3","author":"Provan","year":"2019","journal-title":"Blood Adv."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1182\/bloodadvances.2019000966","article-title":"American Society of Hematology 2019 guidelines for immune thrombocytopenia","volume":"3","author":"Neunert","year":"2019","journal-title":"Blood Adv."},{"key":"ref_3","first-page":"253","article-title":"Recommendations for the management of acute immune thrombocytopenia in children. 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