{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:17:34Z","timestamp":1787897854115,"version":"build-2784847793"},"reference-count":9,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>ATTRv amyloidosis is a progressive multisystem disease caused by pathogenic variants in the transthyretin (TTR) gene. Inotersen is approved for the treatment of polyneuropathy in adults with hereditary transthyretin mediated amyloidosis, but thrombocytopenia is a clinically relevant adverse event that may require treatment interruption or discontinuation. Evidence guiding reintroduction of inotersen after thrombocytopenia is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>We retrospectively reviewed two men with genetically confirmed ATTRv treated at two centers in Argentina who developed treatment-emergent thrombocytopenia during inotersen therapy. Patient 1 was a 71-year-old man with late-onset mixed neurologic and cardiac ATTRv due to TTR p.Val50Met who developed grade 2 thrombocytopenia after 22\u00a0weeks of treatment, with a platelet nadir of 58 \u00d7 10^9\/L. Patient 2 was a 52-year-old man with early-stage neuropathic ATTRv due to TTR p.Val50Met who developed grade 4 thrombocytopenia after 65\u00a0weeks, with platelet counts below 20 \u00d7 10^9\/L, and had recurrent thrombocytopenia during an initial reintroduction attempt.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention and Outcomes<\/jats:title>\n                    <jats:p>After platelet recovery and exclusion of alternative causes of thrombocytopenia, both patients underwent a structured 7-day stepwise short-term reintroduction protocol under close hematologic monitoring. Following protocol completion, inotersen was resumed at 284\u00a0mg every 2\u00a0weeks. During follow-up, neither patient developed recurrent severe thrombocytopenia, and both maintained biochemical evidence of transthyretin suppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this small case series, inotersen reintroduction after thrombocytopenia was feasible in two ATTRv patients when implemented with a structured stepwise protocol and close platelet monitoring, but these findings are hypothesis-generating and not generalizable. One reintroduction occurred outside prescribing recommendations for severe thrombocytopenia and should not be interpreted as a recommended strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1906711","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:33:40Z","timestamp":1787895220000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Inotersen reintroduction after thrombocytopenia in hereditary transthyretin amyloidosis: a case series"],"prefix":"10.3389","volume":"17","author":[{"given":"Cesar A.","family":"Crespi","sequence":"first","affiliation":[{"name":"Centro de Referencia en Enfermedades Raras y de Dificultoso Diagn\u00f3stico (CERyD), Hospital Interzonal Especializado de Agudos y Cr\u00f3nicos San Juan de Dios","place":["La Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Zanga","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Hospital Cesar Milstein","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Florencia","family":"Ardanaz","sequence":"additional","affiliation":[{"name":"Servicio de Alergia, Hospital Interzonal Especializado de Agudos y Cr\u00f3nicos San Juan de Dios","place":["La Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela Pia","family":"Chinigo","sequence":"additional","affiliation":[{"name":"Servicio de Alergia, Hospital Interzonal Especializado de Agudos y Cr\u00f3nicos San Juan de Dios","place":["La Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graciana","family":"Bianco","sequence":"additional","affiliation":[{"name":"Servicio de Farmacia, Hospital Interzonal Especializado de Agudos y Cr\u00f3nicos San Juan de Dios","place":["La Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Del Mar","family":"Iba\u00f1ez Aldecoa","sequence":"additional","affiliation":[{"name":"Servicio de Farmacia, Hospital Interzonal Especializado de Agudos y Cr\u00f3nicos San Juan de Dios","place":["La Plata, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1097\/WCO.0000000000000289","article-title":"First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy","volume":"29","author":"Adams","year":"2016","journal-title":"Curr. 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Syst"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1906711\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:33:40Z","timestamp":1787895220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1906711\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":9,"alternative-id":["10.3389\/fphar.2026.1906711"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1906711","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]},"article-number":"1906711"}}