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Intravascular hemolysis (IVH), increased tendency for thrombosis, and bone marrow failure constitutes hallmark features of the disease and are associated with high morbidity and mortality. The introduction of C5 inhibitors radically changed disease outcomes, offering a near\u2010normal life expectancy to PNH patients. However, residual IVH and extravascular hemolysis (EVH) continue to occur during C5\u2010inhibitor treatment, leaving a significant proportion of patients' anemic and some remaining transfusion dependent. Quality of life (QoL) has also been an issue with the regular intravenous (IV) administrations of the currently licensed C5 inhibitors. This has led to the exploration and development of novel agents, targeting different parts of the complement cascade, or having different formulations allowing for self\u2010administration. Longer\u2010acting and subcutaneous formulations of C5 inhibitors have shown equal safety and efficacy, whereas the development of proximal complement inhibitors is changing completely the therapeutic landscape of PNH, limiting both IVH and EVH and showing superior efficacy over C5 inhibitors, especially in improving haemoglobin. Combination treatments have also been tested with promising results. This review summarizes the current therapeutic options, gaps in anti\u2010complement therapy and discusses emerging therapeutic approaches for PNH.<\/jats:p>","DOI":"10.1002\/ajh.26882","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T08:18:25Z","timestamp":1676535505000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Paroxysmal nocturnal hemoglobinuria: Where are we going"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3180-3570","authenticated-orcid":false,"given":"Austin G.","family":"Kulasekararaj","sequence":"first","affiliation":[{"name":"Department of Hematological Medicine King's College Hospital  London UK"},{"name":"National Institute for Health and Care Research\/Wellcome King's Clinical Research Facility  London UK"},{"name":"Faculty of Life Sciences and Medicine King's College London  London 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