{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:43:01Z","timestamp":1790649781958,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Paroxysmal nocturnal hemoglobinuria (PNH) is an intriguing disease that can pose many difficulties to physicians, as well as to hematologists, who are unfamiliar with it. Research regarding its pathophysiologic, diagnostic, and therapeutic aspects is still ongoing. In the last ten years, new flow cytometry techniques with high sensitivity enabled us to detect PNH clones as small as &lt;1% of a patient\u2019s hematopoiesis, resulting in increasing incidence but more difficult data interpretation. Particularly, the clinical significance of small PNH clones in patients with bone marrow failures, including aplastic anemia and myelodysplastic syndromes, as well as in uncommon associations, such as myeloproliferative disorders, is still largely unknown. Besides current treatment with the anti-C5 eculizumab, which reduced PNH-related morbidity and mortality, new complement inhibitors will likely fulfill unmet clinical needs in terms of patients\u2019 quality of life and better response rates (i.e., responses in subjects with C5 polymorphisms; reduction of extravascular hemolysis and breakthrough hemolysis episodes). Still, unanswered questions remain for these agents regarding their use in mono- or combination therapy, when to treat, and which drug is the best for which patient. Lastly, long-term safety needs to be assessed in real-life studies. In this review, we describe some clinical vignettes illustrating practical aspects of PNH diagnosis and management; moreover, we discuss recent advances in PNH diagnostic and therapeutic approaches.<\/jats:p>","DOI":"10.3390\/jcm10050948","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T10:25:18Z","timestamp":1614594318000},"page":"948","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-8379","authenticated-orcid":false,"given":"Bruno","family":"Fattizzo","sequence":"first","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy"},{"name":"Department of Oncology and Oncohematology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Serpenti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9349-1627","authenticated-orcid":false,"given":"Juri Alessandro","family":"Giannotta","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma","family":"Barcellini","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/asheducation-2016.1.208","article-title":"Update on the diagnosis and management of paroxysmal nocturnal hemoglo binuria","volume":"1","author":"Parker","year":"2016","journal-title":"Hematol. 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