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Herein, we report updated baseline demographics, clinical characteristics, disease burden data, and observed trends regarding clone size in the largest cohort of Registry patients. Patients with available data as of July 2017 were stratified by glycosylphosphatidylinositol (GPI)-deficient granulocyte clone size (&lt;\u200910%, \u2265\u200910%\u2013&lt;\u200950%, and \u2265\u200950%). All patients were untreated with eculizumab at baseline, defined as date of eculizumab initiation or date of Registry enrollment (if never treated with eculizumab). Outcomes assessed in the current analysis included proportions of patients with high disease activity (HDA), history of major adverse vascular events (MAVEs; including thrombotic events [TEs]), bone marrow failure (BMF), red blood cell (RBC) transfusions, and PNH-related symptoms. A total of 4439 patients were included, of whom 2701 (60.8%) had available GPI-deficient granulocyte clone size data. Among these, median clone size was 31.8% (1002 had &lt;\u200910%; 526 had \u2265\u200910%\u2013&lt;\u200950%; 1173 had \u2265\u200950%). There were high proportions of patients with HDA (51.6%), history of MAVEs (18.8%), BMF (62.6%), RBC transfusion (61.3%), and impaired renal function (42.8%). All measures except RBC transfusion history significantly correlated with GPI-deficient granulocyte clone size. A large proportion of patients with GPI-deficient granulocyte clone size &lt;\u200910% had hemolysis (9.7%), MAVEs (10.2%), HDA (9.1%), and\/or PNH-related symptoms. Although larger GPI-deficient granulocyte clone sizes were associated with higher disease burden, a substantial proportion of patients with smaller clone sizes had history of MAVEs\/TEs.<\/jats:p>","DOI":"10.1007\/s00277-020-04052-z","type":"journal-article","created":{"date-parts":[[2020,5,10]],"date-time":"2020-05-10T08:02:40Z","timestamp":1589097760000},"page":"1505-1514","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":153,"title":["Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry"],"prefix":"10.1007","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1222-6659","authenticated-orcid":false,"given":"Hubert","family":"Schrezenmeier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"R\u00f6th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Araten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzuru","family":"Kanakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loree","family":"Larratt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamile M.","family":"Shammo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Shayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw P.","family":"Maciejewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,10]]},"reference":[{"issue":"19","key":"4052_CR1","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1056\/nejm199511093331904","volume":"333","author":"P Hillmen","year":"1995","unstructured":"Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV (1995) Natural history of paroxysmal nocturnal hemoglobinuria. 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Alexander R\u00f6th has received honoraria and consulting fees from Alexion Pharmaceuticals, Inc., Roche, and Novartis, and research support from Alexion Pharmaceuticals, Inc., and Roche. David J. Araten has received honoraria and consulting fees from Alexion Pharmaceuticals, Inc. Yuzuru Kanakura has received honoraria and research support from Alexion Pharmaceuticals, Inc. Loree Larratt has received honoraria and research support (for the laboratory at the University of Alberta, for ADAMTS13 testing) from Alexion Pharmaceuticals, Inc. Jamile M. Shammo has received honoraria, consulting fees, and research support from Alexion Pharmaceuticals, Inc. Amanda Wilson and Gilda Shayan are former employees and stockholders of Alexion Pharmaceuticals, Inc. Jaroslaw P. Maciejewski has received consulting fees from Alexion Pharmaceuticals, Inc., Apellis Pharmaceuticals, and Ra Pharma; has also received speaker fees from Alexion Pharmaceuticals, Inc. and is a member of the Executive Committee of International PNH Registry for Alexion Pharmaceuticals, Inc.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The Registry protocol was approved by an ethics committee for each site, and the Registry is being conducted in compliance with the International Council for Harmonisation Guideline for Good Clinical Practice.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"The institutional review boards (or equivalent) of participating centers approved the Registry, and written informed consent was provided by all patients before study entry.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}