Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul;99(7):1505-1514.
doi: 10.1007/s00277-020-04052-z. Epub 2020 May 10.

Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry

Hubert Schrezenmeier  1   2 , Alexander Röth  3 , David J Araten  4 , Yuzuru Kanakura  5 , Loree Larratt  6 , Jamile M Shammo  7 , Amanda Wilson  8   9 , Gilda Shayan  8   10 , Jaroslaw P Maciejewski  11
Affiliations

Baseline clinical characteristics and disease burden in patients with paroxysmal nocturnal hemoglobinuria (PNH): updated analysis from the International PNH Registry

Hubert Schrezenmeier et al. Ann Hematol. 2020 Jul.

Abstract

The International Paroxysmal Nocturnal Hemoglobinuria (PNH) Registry (NCT01374360) was initiated to optimize patient management by collecting data regarding disease burden, progression, and clinical outcomes. 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 (< 10%, ≥ 10%-< 50%, and ≥ 50%). 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 < 10%; 526 had ≥ 10%-< 50%; 1173 had ≥ 50%). 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 < 10% 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.

Keywords: Bone marrow failure; Eculizumab; Health-related quality of life; Paroxysmal nocturnal hemoglobinuria; Registries; Thrombosis.

PubMed Disclaimer

Conflict of interest statement

Hubert Schrezenmeier has received honoraria and research support (both to University of Ulm) from Alexion Pharmaceuticals, Inc., and honoraria (to University of Ulm) from Ra Pharma, Roche, and Alnylam Pharmaceuticals. Alexander Röth 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.

Figures

Fig. 1
Fig. 1
Proportion of patients with HDA stratified by percentage of GPI-deficient granulocytes at baseline aPatients with available data. GPI glycosylphosphatidylinositol; HDA high disease activity
Fig. 2
Fig. 2
Proportion of patients with a history of (a) MAVEs, TEs (a subset of all MAVEs), or (b) BMF stratified by percentage of GPI-deficient granulocytes at baseline aMAVEs, n = 915; TEs, n = 899; BMF, n = 964. bMAVEs, n = 494; TEs, n = 495; BMF = 509. cMAVEs, n = 1114; TEs, n = 1106; BMF, n = 1125; dPatients with available data. BMF bone marrow failure; GPI glycosylphosphatidylinositol; MAVEs major adverse vascular events; TEs thrombotic events
Fig. 3
Fig. 3
History of physician-reported PNH-related symptoms stratified by percentage of GPI-deficient granulocytes at baseline aFatigue, n = 833; dyspnea, n = 832; hemoglobinuria, n = 829; abdominal pain, n = 832; dysphagia, n = 830; erectile dysfunction, n = 357. bFatigue, n = 426; dyspnea, n = 425; hemoglobinuria, n = 425; abdominal pain, n = 424; dysphagia, n = 426; erectile dysfunction, n = 179. cFatigue, n = 947; dyspnea, n = 947; hemoglobinuria, n = 946; abdominal pain, n = 945; dysphagia, n = 946; erectile dysfunction, n = 443; dPatients with available data. GPI glycosylphosphatidylinositol; PNH paroxysmal nocturnal hemoglobinuria
See this image and copyright information in PMC

References

    1. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333(19):1253–1258. doi: 10.1056/nejm199511093331904. - DOI - PubMed
    1. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804–2811. doi: 10.1182/blood-2014-02-522128. - DOI - PMC - PubMed
    1. Jang JH, Kim JS, Yoon SS, Lee JH, Kim YK, Jo DY, Chung J, Sohn SK, Lee JW. Predictive factors of mortality in population of patients with paroxysmal nocturnal hemoglobinuria (PNH): results from a Korean PNH registry. J Korean Med Sci. 2016;31(2):214–221. doi: 10.3346/jkms.2016.31.2.214. - DOI - PMC - PubMed
    1. Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socie G. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699–3709. doi: 10.1182/blood-2005-04-1717. - DOI - PMC - PubMed
    1. Parker CJ (2011) Management of paroxysmal nocturnal hemoglobinuria in the era of complement inhibitory therapy. Hematology Am Soc Hematol Educ Program 2011:21-29 10.1182/asheducation-2011.1.21 - PubMed

MeSH terms

LinkOut - more resources