Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease classically characterized by chronic intravascular hemolysis, bone marrow failure, and thrombosis. Eculizumab is an anti-C5 monoclonal antibody proven to reduce hemolysis and thrombotic attacks in the treatment of PNH. We aimed to present our data on PNH, a rare disease, and to share our experiences treating PNH with eculizumab. Demographic data, clinical features, history of thrombosis, responses to eculizumab treatment, and survival rates of 9 patients diagnosed with PNH at our hematology center were retrospectively analyzed. The median follow-up period was 46 months (range: 25-62). Five of the patients were female (55.5%), and 4 were male (44.5%), with a median age of 33.5±12.3 years. The mean hemoglobin level was 8.2 g/dL (5.7–10.1 g/dL), mean leukocyte count was 5.80x103/μL (1.72x103/μL–8.30x103/μL), mean platelet count was 96.6x103/L (42x103/μL–214x103/μL), mean lactate dehydrogenase level was 1312 U/L (423–2690 U/L), and mean reticulocyte level was 3.76% (1.1–6.3%). In our study, all cases received eculizumab therapy, of which 8 exhibited full or partial responses, while one was unresponsive to treatment. All patients were alive after the follow-up period. In 8 of the nine patients treated with eculizumab, hemolysis decreased following treatment and blood transfusion was not necessary. The quality of life experienced by all patients was improved. Following determination of the pathogenesis of the PNH, besides the classical treatment methods, eculizumab is a popular treatment option.
___
1. Brodsky RA. Narrative review: paroxysmal nocturnal hemoglobinuria: the physiology of complement-related hemolytic anemia. Ann Intern Med 2008;148:587-95.
2. Bessler M, Mason PJ, Hillmen P, et al. Paroxysmal nocturnal haemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene. EMBO J. 1994;13:110-7.
3. Hillmen P, Richards SJ: Implications of recent insights into the pathophysiology of paroxysmal nocturnal haemoglobinuria. Br J Haematol 2000;108:70-9.
4. Rosse WF: Paroxysmal nocturnal hemoglobinuria as a molecular disease. Medicine (Baltimore). 1997;76:63-93.
5. Socié G, Mary JY, de Gramont A, et al; French Society of Haematology. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996;348:573-7.
6. Borowitz MJ, Craig FE, Digiuseppe JA, et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin Cytom. 2010;78:211-30.
7. Dirik Y, Ekinci Ö, Kara O, et al. The role of paroxysmal nocturnal hemoglobinuria in idiopathic habitual abortion. East J Med. 2017;22:143-6.
8. Hillmen P, Lewis SM, Bessler M, et al. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-8.
9. Ekinci Ö, Doğan A, Demir C. The presence of paroxysmal nocturnal hemoglobinuria in patients with idiopathic chronic renal failure. East J Med. 2017;22:133-6.
10. Schubert J, Hillmen P, Roth A, et al. Eculizumab, a terminal complement inhibitor, improves anaemia in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2008;142:263-72.
11. Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117:6786-92.
12. Rose WF, Schrier SL, Landaw SA. Clinical manifestations of paroxysmal nocturnal hemoglobinuria. Review version 18.3. Up to date, 2010.
13. Karadimitris A, Araten DJ, Luzzatto L, et al. Severe telomere shortening in patients with paroxysmal nocturnal hemoglobinuri a affects both GPI- and GPI+ hematopoiesis. Blood. 2003;102:514-6.
14. Hillmen P, Elebute P, Kelly R, et al. Longterm effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2010;85:553-9.
15. Parker C, Omine M, Richards S, et al. International PNH Interest Group. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106:3699-709.
16. Hall C, Richards S, Hillmen P. Primaryprophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH). Blood 2003;102:3587-91.
17. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2006;355:1233-43.
18. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124 2804-11.
19. Hillmen P, Muus P, Röth A, et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013;162:62-73.