Richards SJ, Painter D, Dickinson AJ, Griffin M, Munir T, Arnold L, et al. The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: a retrospective analysis of the UK’s population-based haematological malignancy research network 2004–2018. Eur J Haematol. 2021;107:211–8.

Article  PubMed  Google Scholar 

Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253–8.

Article  PubMed  Google Scholar 

Holguin MH, Fredrick LR, Bernshaw NJ, Wilcox LA, Parker CJ. Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria. J Clin Investig. 1989;84:7–17.

Article  PubMed  PubMed Central  Google Scholar 

Rollins SA, Sims PJ. The complement-inhibitory activity of CD59 resides in its capacity to block incorporation of C9 into membrane C5b–9. J Immunol. 1990;144:3478–83.

Article  PubMed  Google Scholar 

Varela JC, Tomlinson S. Complement: an overview for the clinician. Hematol Oncol Clin N Am. 2015;29:409–27.

Article  Google Scholar 

Hillmen P, Hows JM, Luzzatto L. Two distinct patterns of glycosylphosphatidylinositol (GPI) linked protein deficiency in the red cells of patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1992;80:399–405.

Article  PubMed  Google Scholar 

Nakakuma H, Nagakura S, Horikawa K, Hidaka M, Kawaguchi T, Iwamoto N, et al. Interleukin-2-dependent T-cell lines established from paroxysmal nocturnal hemoglobinuria patients. Blood. 1994;84:309–14.

Article  PubMed  Google Scholar 

Schubert J, Uciechowski P, Delany P, Tischler HJ, Kolanus W, Schmidt RE. The PIG-anchoring defect in NK lymphocytes of PNH patients. Blood. 1990;76:1181–7.

Article  PubMed  Google Scholar 

Vidugiriene J, Menon AK. Early lipid intermediates in glycosyl-phosphatidylinositol anchor assembly are synthesized in the ER and located in the cytoplasmic leaflet of the ER membrane bilayer. J Cell Biol. 1993;121:987–96.

Article  PubMed  Google Scholar 

Medof ME, Kinoshita T, Silber R, Nussenzweig V. Amelioration of lytic abnormalities of paroxysmal nocturnal hemoglobinuria with decay-accelerating factor. Proc Natl Acad Sci USA. 1985;82:2980–4.

Article  PubMed  PubMed Central  Google Scholar 

Walport MJ. Complement. First of two parts. N Engl J Med. 2001;344:1058–66.

Article  PubMed  Google Scholar 

Rosse WF. Variations in the red cells in paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1973;24:327–42.

Article  PubMed  Google Scholar 

Rosse WF, Adams JP, Thorpe AM. The population of cells in paroxysmal nocturnal haemoglobinuria of intermediate sensitivity to complement lysis: significance and mechanism of increased immune lysis. Br J Haematol. 1974;28:181–90.

Article  PubMed  Google Scholar 

Langemeijer S, Schaap C, Preijers F, Jansen JH, Blijlevens N, Inoue N, et al. Paroxysmal nocturnal hemoglobinuria caused by CN-LOH of constitutional PIGB mutation and 70-kbp microdeletion on 15q. Blood Adv. 2020;4:5755–61.

PubMed  PubMed Central  Google Scholar 

Costa JR, Caputo VS, Makarona K, Layton DM, Roberts IAG, Almeida AM, et al. Cell-type–specific transcriptional regulation of PIGM underpins the divergent hematologic phenotype in inherited GPl deficiency. Blood. 2014;124:3151–4.

Article  PubMed  PubMed Central  Google Scholar 

Höchsmann B, Murakami Y, Osato M, Knaus A, Kawamoto M, Inoue N, et al. Complement and inflammasome overactivation mediates paroxysmal nocturnal hemoglobinuria with autoinflammation. J Clin Investig. 2019;129:5123–36.

Article  PubMed  PubMed Central  Google Scholar 

Almeida AM, Murakami Y, Layton DM, Hillmen P, Sellick GS, Maeda Y, et al. Hypomorphic promoter mutation in PIGM causes inherited glycosylphosphatidylinositol deficiency. Nat Med. 2006;12:846–50.

Article  PubMed  Google Scholar 

Kinoshita T, Ohishi K, Takeda J. GPI-anchor synthesis in mammalian cells: genes, their products, and a deficiency. J Biochem. 1997;122:251–725.

Article  PubMed  Google Scholar 

Krawitz PM, Höchsmann B, Murakami Y, Teubner B, Krüger U, Klopocki E, et al. A case of paroxysmal nocturnal hemoglobinuria caused by a germline mutation and a somatic mutation in PIGT. Blood. 2013;122:1099–100.

Article  Google Scholar 

Araten DJ, Bessler M, McKenzie S, Castro-Malaspina H, Childs BH, Boulad F, et al. Dynamics of hematopoiesis in paroxysmal nocturnal hemoglobinuria (PNH): no evidence for intrinsic growth advantage of PNH clones. Leukemia. 2002;16:2243–8.

Article  PubMed  Google Scholar 

Araten DJ, Luzzatto L. The mutation rate in PIG-A is normal in patients with paroxysmal nocturnal hemoglobinuria (PNH). Blood. 2006;108:734–6.

Article  PubMed  PubMed Central  Google Scholar 

Young NS, Maciejewski JP, Sloand E, Chen G, Zeng W, Risitano A, et al. The relationship of aplastic anemia and PNH. Int J Hematol. 2002;76(Supplement 2):168–72.

Article  PubMed  Google Scholar 

Colden MA, Kumar S, Munkhbileg B, Babushok DV. Insights into the emergence of paroxysmal nocturnal hemoglobinuria. Front Immunol. 2022;12:830172. https://doi.org/10.3389/fimmu.2021.830172.

Article  PubMed  PubMed Central  Google Scholar 

Brodsky RA, Vala MS, Barber JP, Medof ME, Jones RJ. Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci USA. 1997;94:8756–60.

Article  PubMed  PubMed Central  Google Scholar 

Inoue N, Murakami Y, Kinoshita T. Molecular genetics of paroxysmal nocturnal hemoglobinuria. Int J Hematol. 2003;77:107–12.

Article  PubMed  Google Scholar 

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 (Baltimore). 2004;83:193–207.

Article  PubMed  Google Scholar 

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.

Article  PubMed  Google Scholar 

Kelly RJ, Holt M, Vidler J, Arnold LM, Large J, Forrest B, et al. Treatment outcomes of complement protein C5 inhibition in 509 UK patients with paroxysmal nocturnal hemoglobinuria. Blood. 2024;21(143):1157–66.

Article  Google Scholar 

Borowitz MJ, Craig FE, DiGiuseppe JA, Illingworth AJ, Rosse W, Sutherland R, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytom B Clin Cytom. 2010;78B:211–30.

Article  Google Scholar 

Sutherland DR, Kuek N, Davidson J, Barth D, Chang H, Yeo E, et al. Diagnosing PNH with FLAER and multiparameter flow cytometry. Cytom B Clin Cytom. 2007;72:167–77.

Article  Google Scholar 

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.

Article  PubMed  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

Moyo VM, Mukhina GL, Garrett ES, Brodsky RA. Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol. 2004;126:133–8.

Article  PubMed  Google Scholar 

Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA. 2005;293:1653–1562.

Article  PubMed  Google Scholar 

Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004;350:886–95.

Article  PubMed