{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:05:37Z","timestamp":1791925537958,"version":"4.3.4"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"15-16","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Wien Klin Wochenschr"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematologic disorder characterized by a\u00a0loss of glycosyl-phosphatidyl-inositol-linked (GPI) proteins on various hematopoietic cells. Some GPI proteins are involved in the regulation of the complement system, and their absence renders erythrocytes susceptible to complement-mediated lysis. Current standard of care in PNH is to block the complement system at the level of C5 using ravulizumab or eculizumab; however, some patients with PNH may develop extravascular hemolysis (EVH) during treatment with C5 inhibitors. The proximal complement inhibitor iptacopan has recently been shown to be efficacious in patients with PNH. This article reports on a\u00a043-year-old female patient with PNH who was successfully treated with iptacopan. The patient had received ravulizumab for several years and developed a\u00a0clinically relevant EVH. After obtaining informed consent, the patient received oral iptacopan 200\u202fmg twice daily and ravulizumab was discontinued. Over the next few weeks hemoglobin levels and reticulocyte counts normalized. The patient reported mild flushes with erythema, chills, and mild muscle pain, all of which resolved during follow-up. No breakthrough hemolysis occurred, and no severe adverse events were recorded.<\/jats:p>","DOI":"10.1007\/s00508-024-02390-w","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T05:24:26Z","timestamp":1719897866000},"page":"472-475","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Resolution of extravascular hemolysis with oral iptacopan monotherapy in a\u00a0patient with treatment experienced paroxysmal nocturnal hemoglobinuria (PNH)"],"prefix":"10.1007","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-4822","authenticated-orcid":false,"given":"Wolfgang","family":"F\u00fcreder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Thalhammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Valent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"issue":"19","key":"2390_CR1","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1056\/NEJM199511093331904","volume":"333","author":"P Hillmen","year":"1995","unstructured":"Hillmen\u00a0P, Lewis\u00a0SM, Bessler\u00a0M, Luzzatto\u00a0L, Dacie\u00a0JV. Natural history of paroxysmal nocturnal hemoglobinuria. N\u00a0Engl J Med. 1995;333(19):1253\u20138.","journal-title":"N Engl J Med"},{"issue":"12","key":"2390_CR2","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1056\/NEJMoa061648","volume":"355","author":"P Hillmen","year":"2006","unstructured":"Hillmen\u00a0P, Young\u00a0NS, Schubert\u00a0J, Brodsky\u00a0RA, Soci\u00e9\u00a0G, Muus\u00a0P, et\u00a0al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N\u00a0Engl J Med. 2006;355(12):1233\u201343.","journal-title":"N Engl J Med"},{"issue":"3","key":"2390_CR3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1111\/ejh.13783","volume":"109","author":"AG Kulasekararaj","year":"2022","unstructured":"Kulasekararaj\u00a0AG, Griffin\u00a0M, Langemeijer\u00a0S, Usuki\u00a0K, Kulagin\u00a0A, Ogawa\u00a0M, et\u00a0al. Long-term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2\u2011year results from two pivotal phase\u00a03\u00a0studies. Eur J Haematol. 2022;109(3):205\u201314.","journal-title":"Eur J Haematol"},{"issue":"17","key":"2390_CR4","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.1182\/blood-2008-11-189944","volume":"113","author":"AM Risitano","year":"2009","unstructured":"Risitano\u00a0AM, Notaro\u00a0R, Marando\u00a0L, Serio\u00a0B, Ranaldi\u00a0D, Seneca\u00a0E, et\u00a0al. Complement fraction 3 binding on erythrocytes as additional mechanism of disease in paroxysmal nocturnal hemoglobinuria patients treated by eculizumab. Blood. 2009;113(17):4094\u2013100.","journal-title":"Blood"},{"key":"2390_CR5","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1056\/NEJMra2201664","volume":"387","author":"R Notaro","year":"2022","unstructured":"Notaro\u00a0R, Luzzatto\u00a0L. Breakthrough Hemolysis in PNH with Proximal or Terminal Complement Inhibition. N\u00a0Engl J Med. 2022;387:160\u20136.","journal-title":"N Engl J Med"},{"issue":"11","key":"2390_CR6","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1056\/NEJMoa2029073","volume":"384","author":"P Hillmen","year":"2021","unstructured":"Hillmen\u00a0P, Szer\u00a0J, Weitz\u00a0I, R\u00f6th\u00a0A, H\u00f6chsmann\u00a0B, Panse\u00a0J, et\u00a0al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N\u00a0Engl J Med. 2021;384(11):1028\u201337.","journal-title":"N Engl J Med"},{"issue":"12","key":"2390_CR7","doi-asserted-by":"publisher","first-page":"e955","DOI":"10.1016\/S2352-3026(23)00315-0","volume":"10","author":"JW Lee","year":"2023","unstructured":"Lee\u00a0JW, Griffin\u00a0M, Kim\u00a0JS, Lee\u00a0LLW, Piatek\u00a0C, Nishimura\u00a0JI, et\u00a0al. Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a\u00a0double-blind, randomised, phase\u00a03\u00a0trial. Lancet Haematol. 2023;10(12):e955\u2013e65.","journal-title":"Lancet Haematol"},{"issue":"11","key":"2390_CR8","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1056\/NEJMoa2308695","volume":"390","author":"R Peffault de Latour","year":"2024","unstructured":"Peffault de Latour\u00a0R, R\u00f6th\u00a0A, Kulasekararaj\u00a0AG, Han\u00a0B, Scheinberg\u00a0P, Maciejewski\u00a0JP, et\u00a0al. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria. N\u00a0Engl J Med. 2024;390(11):994\u20131008.","journal-title":"N Engl J Med"}],"container-title":["Wiener klinische Wochenschrift"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00508-024-02390-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00508-024-02390-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00508-024-02390-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T09:20:31Z","timestamp":1723713631000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00508-024-02390-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":8,"journal-issue":{"issue":"15-16","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["2390"],"URL":"https:\/\/doi.org\/10.1007\/s00508-024-02390-w","relation":{},"ISSN":["0043-5325","1613-7671"],"issn-type":[{"value":"0043-5325","type":"print"},{"value":"1613-7671","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,1]]},"assertion":[{"value":"27 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"W.\u00a0F\u00fcreder has received honoraria from Alexion, Apellis, BioCryst, Novartis, Roche and Sobi. R.\u00a0Thalhammer declares that she has no competing interests. P.\u00a0Valent has received honoraria from Alexion, Amgen and Novartis.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}