Abstract
A difference in clinical manifestations of paroxysmal nocturnal hemoglobinuria (PNH) among different races has been suggested. The aim of this study was to clarify whether the clinical characteristics of patients with PNH in the International PNH Registry differ by ethnic background. Patients, who were eculizumab naïve at baseline and had ≥ 1% PNH clone size, were eligible for this analysis. Totally, 1793 patients were enrolled and divided into two cohorts, Asian (N = 246) and non-Asian (N = 1547). The Asian cohort was further divided into Asians in Asia cohort (N = 202) and Asians in non-Asia cohort (N = 44), based on geographical region. The Asian cohort had significantly higher PNH clone size in granulocytes, higher lactate dehydrogenase levels, and lower hemoglobin levels. However, the frequencies of symptoms including abdominal pain, backache, easy bleeding, fatigue and headache at baseline were significantly lower in the Asian cohort. The proportion of patients with a history of thromboembolism (TE) was significantly lower in the Asian than in the non-Asian cohort (3.6% vs. 8.9%, P < 0.01); however, there was no difference between Asians in Asia and Asians in non-Asia (3.3% vs. 4.9%, P = 0.61). These findings suggested that genetic factors may play a stronger role in developing TE than lifestyle factors in PNH patients.
Similar content being viewed by others
References
Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253–8.
Miyata T, Takeda J, Iida Y, Yamada N, Inoue N, Takahashi M, et al. The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis. Science. 1993;259:1318–20.
Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:3699–709.
Takeda J, Miyata T, Kawagoe K, Iida Y, Endo Y, Fujita T, et al. Deficiency of the GPI anchor caused by a somatic mutation of the PIG-A gene in paroxysmal nocturnal hemoglobinuria. Cell. 1993;73:703–11.
Nishimura J, Kanakura Y, Ware RE, Shichishima T, Nakakuma H, Ninomiya H, et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine. 2004;83:193–207.
Socie G, Mary JY, de Gramont A, Rio B, Leporrier M, Rose C, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996;348:573–7.
Hillmen P, Hall C, Marsh JC, Elebute M, Bombara MP, Petro BE, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004;350:552–9.
Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233–43.
Brodsky RA, Young NS, Antonioli E, Risitano AM, Schrezenmeier H, Schubert J, et al. Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria. Blood. 2008;111:1840–7.
Ueda Y, Obara N, Yonemura Y, Noji H, Masuko M, Seki Y, et al. Effects of eculizumab treatment on quality of life in patients with paroxysmal nocturnal hemoglobinuria in Japan. Int J Hematol. 2018;107:656–65.
Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117:6786–92.
Schrezenmeier H, Muus P, Socie G, Szer J, Urbano-Ispizua A, Maciejewski JP, et al. Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. Haematologica. 2014;99:922–9.
Socie G, Schrezenmeier H, Muus P, Lisukov I, Röth A, Kulasekararaj A, et al. Changing prognosis in paroxysmal nocturnal haemoglobinuria disease subcategories: an analysis of the International PNH Registry. Intern Med J. 2016;46:1044–53.
Chou WC, Huang WH, Wang MC, Chang CS, Yeh SP, Chiou TJ, et al. Characteristics of Taiwanese patients of PNH in the international PNH registry. Thromb J. 2016;14(Suppl 1):39.
de Latour RP, Mary JY, Salanoubat C, Terriou L, Etienne G, Mohty M, et al. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood. 2008;112:3099–106.
Jang JH, Kim JS, Yoon SS, Lee JH, Kim YK, Jo DY, et al. Predictive factors of mortality in population of patients with paroxysmal nocturnal hemoglobinuria (PNH): results from a Korean PNH Registry. J Korean Med Sci. 2016;31:214–21.
Munoz-Linares C, Ojeda E, Fores R, Pastrana M, Cabero M, Morillo D, et al. Paroxysmal nocturnal hemoglobinuria: a single Spanish center’s experience over the last 40 yr. Eur J Haematol. 2014;93:309–19.
Lee JW, Jang JH, Kim JS, Yoon SS, Lee JH, Kim YK, et al. Clinical signs and symptoms associated with increased risk for thrombosis in patients with paroxysmal nocturnal hemoglobinuria from a Korean Registry. Int J Hematol. 2013;97:749–57.
Wang HC, Kuo CY, Liu IT, Chen TY, Chang YH, Lin SJ, et al. Distinct clinical characteristics of paroxysmal nocturnal hemoglobinuria in patients in Southern Taiwan: a multicenter investigation. Kaohsiung J Med Sci. 2017;33:405–10.
Yu F, Du Y, Han B. A comparative analysis of clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria between Asia and Europe/America. Int J Hematol. 2016;103:649–54.
Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood. 2013;121:4985–96.
Rosse WF. Treatment of paroxysmal nocturnal hemoglobinuria. Blood. 1982;60:20–3.
Issaragrisil S, Piankijagum A, Tang-naitrisorana Y. Corticosteroids therapy in paroxysmal nocturnal hemoglobinuria. Am J Hematol. 1987;25:77–83.
Shichishima T, Saitoh Y, Noji H, Terasawa T, Maruyama Y. In vivo effects of various therapies on complement-sensitive erythrocytes in paroxysmal nocturnal hemoglobinuria. Int J Hematol. 1996;63:291–302.
Acknowledgements
We are grateful to all doctors and paramedics who reported data to the International PNH Registry. The study was funded and analyzed by Alexion Pharmaceutical, Inc.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
MS, JN, YK, JWL and SO receive honoraria from Alexion, JN, YK and JWL receive research funding from Alexion Pharma G.K., AW receives employment, and equity ownership from Alexion Pharmaceuticals, Inc.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Sakurai, M., Jang, J.H., Chou, WC. et al. Comparative study on baseline clinical characteristics of Asian versus non-Asian patients with paroxysmal nocturnal hemoglobinuria. Int J Hematol 110, 411–418 (2019). https://doi.org/10.1007/s12185-019-02699-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-019-02699-7