Economic Burden of Paroxysmal Nocturnal Hemoglobinuria (PNH) and Secondary Problems Caused by PNH
Economic Burden of PNH Patients
Abstract
Background: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired disorder of hematopoietic stem cells, in which red blood cells become susceptible to complement-mediated hemolysis. PNH is associated with a wide range of medical consequences and costs. This study was done to estimate the economic burden of PNH and the secondary consequences caused by PNH in Iran.Methods: This study is a cross-sectional and non-interventional study conducted using the cost-of-illness framework. The top-down prevalence method was used to quantify the annual PNH-related costs. This study was conducted from the societal perspective, including all direct medical, non-medical, and indirect costs associated with PNH. Productivity losses were calculated using the human capital method. Costs were collected using the relative value unit of health services in Iran, related literature, and from one of the referral hospitals in Iran, as well. Results: The average annual costs of blood transfusion and anemia, thromboembolic events, and renal problems are estimated to be around $5400, $5382, and $6422, respectively. The total average costs of the three mentioned consequences caused by PNH are estimated to be $17,204 US dollars per PNH patient per year in Iran.Conclusion: This study suggests that the average cost of managing anemia, blood transfusion, thromboembolic events, and renal problems in PNH equals $17,204 annually. Dependent on the severity of the disease and other factors, this amount could increase significantly. Additional cost-effectiveness studies should be carried out to identify the most cost-efficient disease management protocol.
[1] Hill A, Rother RP, Wang X, Morris SM Jr, Quinn-Senger K, Kelly R, et al. Effect of eculizumab on haemolysis -associated nitric oxide deple-tion, dyspnoea, and measures of pulmonary hypertension in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2010; 149(3):414-25. [DOI:10.1111/j.1365-2141.2010.08096.x] [PMID]
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[3] Hu R, Mukhina GL, Piantadosi S, Barber JP, Jones RJ, Brodsky RA. PIGA mutations in normal hematopoiesis. Blood. 2005; 105(10):3848-54. [DOI:10.1182/blood-2004-04-1472] [PMID] [PMCID] [4] Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005; 106(12):3699-709. [DOI:10.1182/blood-2005-04-1717] [PMID] [PMCID]
[5] Gulbis B, Eleftheriou A, Angastiniotis M, Ball S, Surrallés J, CastellaM, et al. Epidemiology of rare anaemias in Europe. Adv Exp Med Biol. 2010; 686:375-96. [PMID]
[6] Socié G, Mary JY, de Gramont A, Rio B, Leporrier M, Rose C, et al. Paroxysmal nocturnal haemoglobinuria: Long-term follow-up and prognostic factors. Lancet. 1996; 348(9027):573-7. [DOI:10.1016/S0140-6736(95)12360-1]
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[8] 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. New EnglJ Med. 2004; 350(6):552-9. [DOI:10.1056/NEJMoa031688] [PMID]
[9] Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. New Engl J Med. 2006; 355(12):1233-43. [DOI:10.1056/NEJMoa061648] [PMID]
[10] 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(4):1840-7. [DOI:10.1182/blood-2007-06-094136] [PMID]
[11] Emamgholipour S, Akbari Sari A, Geravandi S, Mazrae H. [Estimation of out-of-pocket and catastrophic expenditures among patients with cardiovascular diseases in Khuzestan (Persian)]. J Payavard Salamat. 2017; 11(3):297-307. http://payavard.tums.ac.ir/article-1-6289-en.html
[12] Max W, Rice DP, Sung HY, Michel M, Breuer W, Zhang X. The economic burden of prostate cancer, California, 1998. Cancer. 2002; 94(11):2906-13. [DOI:10.1002/cncr.10532] [PMID]
[13] Javadi M, Asgari H, Yaghoobbi M, Tavazohi H. [Self-assessment of the non-communicable disease surveillance system in Medical University of Isfahan based on the model suggested by the World Health Organization (Persian)]. J Sch Public Health Inst Public Health Res. 2010; 8(3):47-60. http://sjsph.tums.ac.ir/article-1-77-en.html
[14] World Health Organization (WHO). National cancer control programmes: Policies and managerial guidelines. Geneva: World Health Organization; 2002. https://apps.who.int/iris/handle/10665/42494
[15] de Latour RP, Schrezenmeier H, Bacigalupo A, et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica. 2012; 97(11):1666-73. [DOI:10.3324/haema tol.2012.062828] [PMID] [PMCID]
[16] Sašo R, Marsh J, Cevreska L, Szer J, Gale RP, Rowlings PA, et al. Bone marrow transplants for paroxysmal nocturnal haemoglobi nuria. Br J Haematol. 1999; 104(2):392-6. [DOI:10.1046/j.1365-2141.1999.01195.x] [PMID]
[17] Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J, et al. A systematic review and economic evaluation of epoetin alfa, epoetin beta and darbepoetin alfa in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess. 2007; 11(13):1-202. [DOI:10.3310/hta11130] [PMID]
[18] Toner RW, Pizzi L, Leas B, Ballas SK, Quigley A, Goldfarb NI. Costs to hospitals of acquiring and processing blood in the US: A survey of hospital-based blood banks and transfusion services. Appl Health Econ Health Policy. 2011; 9(1):29-37. [DOI:10.2165/11530740-000000000-00000] [PMID]
[19] Moyo VM, Mukhina GL, Garrett ES, Brodsky RA. Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol. 2004; 126(1):133-8. [DOI:10.1111/j.13652141.2004.04992.x] [PMID]
[20] Araten DJ, Thaler HT, Luzzatto L. High incidence of thrombosis in African-American and Latin-American patients with paroxysmal nocturnal haemoglobinuria. Thromb Haemost. 2005; 93(1):88-91. [DOI:10.1160/TH04-06-0391] [PMID]
[21] 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(8):3099-3106. [DOI:10.1182/blood-2008-01-133918] [PMID]
[22] Gralnick HR, Vail M, McKeown LP, Merryman P, Wilson O, Chu I, et al. Activated platelets in paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1995; 91(3):697-702. [DOI:10.1111/j.1365-2141.1995.tb05371.x] [PMID]
[23] Ray JG, Burows RF, Ginsberg JS, Burrows EA. Paroxysmal nocturnal hemoglobinuria and the risk of venous thrombosis: Review and recommendations for management of the pregnant and nonpregnant patient. Haemostasis. 2000; 30(3):103-17. [DOI:10.1159/000022532] [PMID]
[24] Nishimura JI, 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(3):193-207. [DOI:10.1097/01.md.0000126763.68170.46] [PMID]
[25] Schrezenmeier H, Muus P, Socié 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(5):922-9. [PMID]
[26] Zachée P, Henckens M, Van Damme B, Boogaerts MA, Rigauts H, Verberckmoes RK. Chronic renal failure due to renal hemosiderosis in a patient with paroxysmal nocturnal hemoglobinuria. Clin Nephrol. 1993; 39(1):28-31. [PMID]
[27] Clark DA, Butler SA, Braren V, Hartmann RC, Jenkins DE Jr. The kidneys in paroxysmal nocturnal hemoglobinuria. Blood. 1981; 57(1):83-9. [PMID]
[28] Riley AL, Ryan LM, Roth DA. Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria. Am J Med. 1977; 62(1):125-9. [DOI:10.1016/0002-9343(77)90357-6]
[29] Hsiao PJ, Wang SC, Wen MC, Diang LK, Lin SH. Fanconi syndrome and CKD in a patient with paroxysmal nocturnal hemoglobinuria and hemosiderosis. Am J Kidney Dis. 2010; 55(1):e1-5. [DOI:10.1053/j.ajkd.2009.07.022] [PMID]
[30] Mathieu D, Rahmouni A, Villeneuve P, Anglade MC, Rochant H, Vasile N. Impact of magnetic resonance imaging on the diagnosis of abdominal complications of paroxysmal nocturnal hemoglobin ria. Blood. 1995; 85(11):3283-8. [DOI:10.1182/blood.V85.11.3283.bloodjournal85113283] [PMID]
[31] Mulopulos GP, Turner DA, Schwartz MM, Murakami ME, Clark JW. MRI of the kidneys in paroxysmal nocturnal hemoglobinuria. AJR Am J Roentgenol. 1986; 146(1):51-2. [DOI:10.2214/ajr.146.1.51 ] [PMID]
[32] Nguyen JS, Marinopoulos SS, Ashar BH, Flynn JA. Clinical problem-solving. More than meets the eye. N Engl J Med. 2006; 355(10):1048-52. [DOI:10.1056/NEJMcps044359] [PMID]
[33] Rimola J, Martín J, Puig J, Darnell A, Massuet A. The kidney in paroxysmal nocturnal haemoglobinuria: MRI findings. Br J Radiol. 2004; 77(923):953-6. [DOI:10.1259/bjr/51760601] [PMID]
[34] Suzukawa K, Ninomiya H, Mitsuhashi S, Anno I, Nagasawa T, Abe T. Demonstration of the deposition of hemosiderin in the kidneys of patients with paroxysmal nocturnal hemoglobinuria by magnetic resonance imaging. Intern Med. 1993; 32(9):686-90. [DOI:10.2169/internalmedicine.32.686] [PMID]
[35] Tanaka YO, Anno I, Itai Y, Abe T. Paroxysmal nocturnal hemoglobinuria: MR findings. J Comput Assisted Tomogr. 1993; 17(5):749-53. [DOI:10.1097/00004728-199309000-00016] [PMID]
[36] Nath KA, Vercellotti GM, Grande JP, Miyoshi H, Paya CV, Manivel JC, et al. Heme protein-induced chronic renal inflammation: Suppressive effect of induced heme oxygenase-1. Kidney Int. 2001; 59(1):106-17. [DOI:10.1046/j.1523-1755.2001.00471.x] [PMID]
[37] Hillmen P, Elebute M, Kelly R, Urbano-Ispizua A, Hill A, Rother RP, et al. Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2010; 85(8):553-9. [DOI:10.1002/ajh.21757] [PMID]
[38] Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney func-tion-measured and estimated glomerular filtration rate. N Engl J Med. 2006; 354(23):2473-83. [DOI:10.1056/NEJMra054415] [PMID]
[2] Luzzatto L, Gianfaldoni G. Recent advances in biological and clinical aspects of paroxysmal nocturnal hemoglobinuria. Int J Hematol. 2006; 84(2):104-12. [DOI:10.1532/IJH97.06117] [PMID]
[3] Hu R, Mukhina GL, Piantadosi S, Barber JP, Jones RJ, Brodsky RA. PIGA mutations in normal hematopoiesis. Blood. 2005; 105(10):3848-54. [DOI:10.1182/blood-2004-04-1472] [PMID] [PMCID] [4] Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005; 106(12):3699-709. [DOI:10.1182/blood-2005-04-1717] [PMID] [PMCID]
[5] Gulbis B, Eleftheriou A, Angastiniotis M, Ball S, Surrallés J, CastellaM, et al. Epidemiology of rare anaemias in Europe. Adv Exp Med Biol. 2010; 686:375-96. [PMID]
[6] Socié G, Mary JY, de Gramont A, Rio B, Leporrier M, Rose C, et al. Paroxysmal nocturnal haemoglobinuria: Long-term follow-up and prognostic factors. Lancet. 1996; 348(9027):573-7. [DOI:10.1016/S0140-6736(95)12360-1]
[7] Hill A, Platts PJ, Smith A, Richards SJ, Cullen MJ, Hill QA, et al. The incidence and prevalence of paroxysmal nocturnal hemoglobinuria (PNH) and survival of patients in Yorkshire. Blood. 2006; 108(11):985. [DOI:10.1182/blood.V108.11.985.985]
[8] 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. New EnglJ Med. 2004; 350(6):552-9. [DOI:10.1056/NEJMoa031688] [PMID]
[9] Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. New Engl J Med. 2006; 355(12):1233-43. [DOI:10.1056/NEJMoa061648] [PMID]
[10] 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(4):1840-7. [DOI:10.1182/blood-2007-06-094136] [PMID]
[11] Emamgholipour S, Akbari Sari A, Geravandi S, Mazrae H. [Estimation of out-of-pocket and catastrophic expenditures among patients with cardiovascular diseases in Khuzestan (Persian)]. J Payavard Salamat. 2017; 11(3):297-307. http://payavard.tums.ac.ir/article-1-6289-en.html
[12] Max W, Rice DP, Sung HY, Michel M, Breuer W, Zhang X. The economic burden of prostate cancer, California, 1998. Cancer. 2002; 94(11):2906-13. [DOI:10.1002/cncr.10532] [PMID]
[13] Javadi M, Asgari H, Yaghoobbi M, Tavazohi H. [Self-assessment of the non-communicable disease surveillance system in Medical University of Isfahan based on the model suggested by the World Health Organization (Persian)]. J Sch Public Health Inst Public Health Res. 2010; 8(3):47-60. http://sjsph.tums.ac.ir/article-1-77-en.html
[14] World Health Organization (WHO). National cancer control programmes: Policies and managerial guidelines. Geneva: World Health Organization; 2002. https://apps.who.int/iris/handle/10665/42494
[15] de Latour RP, Schrezenmeier H, Bacigalupo A, et al. Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. Haematologica. 2012; 97(11):1666-73. [DOI:10.3324/haema tol.2012.062828] [PMID] [PMCID]
[16] Sašo R, Marsh J, Cevreska L, Szer J, Gale RP, Rowlings PA, et al. Bone marrow transplants for paroxysmal nocturnal haemoglobi nuria. Br J Haematol. 1999; 104(2):392-6. [DOI:10.1046/j.1365-2141.1999.01195.x] [PMID]
[17] Wilson J, Yao GL, Raftery J, Bohlius J, Brunskill S, Sandercock J, et al. A systematic review and economic evaluation of epoetin alfa, epoetin beta and darbepoetin alfa in anaemia associated with cancer, especially that attributable to cancer treatment. Health Technol Assess. 2007; 11(13):1-202. [DOI:10.3310/hta11130] [PMID]
[18] Toner RW, Pizzi L, Leas B, Ballas SK, Quigley A, Goldfarb NI. Costs to hospitals of acquiring and processing blood in the US: A survey of hospital-based blood banks and transfusion services. Appl Health Econ Health Policy. 2011; 9(1):29-37. [DOI:10.2165/11530740-000000000-00000] [PMID]
[19] Moyo VM, Mukhina GL, Garrett ES, Brodsky RA. Natural history of paroxysmal nocturnal haemoglobinuria using modern diagnostic assays. Br J Haematol. 2004; 126(1):133-8. [DOI:10.1111/j.13652141.2004.04992.x] [PMID]
[20] Araten DJ, Thaler HT, Luzzatto L. High incidence of thrombosis in African-American and Latin-American patients with paroxysmal nocturnal haemoglobinuria. Thromb Haemost. 2005; 93(1):88-91. [DOI:10.1160/TH04-06-0391] [PMID]
[21] 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(8):3099-3106. [DOI:10.1182/blood-2008-01-133918] [PMID]
[22] Gralnick HR, Vail M, McKeown LP, Merryman P, Wilson O, Chu I, et al. Activated platelets in paroxysmal nocturnal haemoglobinuria. Br J Haematol. 1995; 91(3):697-702. [DOI:10.1111/j.1365-2141.1995.tb05371.x] [PMID]
[23] Ray JG, Burows RF, Ginsberg JS, Burrows EA. Paroxysmal nocturnal hemoglobinuria and the risk of venous thrombosis: Review and recommendations for management of the pregnant and nonpregnant patient. Haemostasis. 2000; 30(3):103-17. [DOI:10.1159/000022532] [PMID]
[24] Nishimura JI, 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(3):193-207. [DOI:10.1097/01.md.0000126763.68170.46] [PMID]
[25] Schrezenmeier H, Muus P, Socié 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(5):922-9. [PMID]
[26] Zachée P, Henckens M, Van Damme B, Boogaerts MA, Rigauts H, Verberckmoes RK. Chronic renal failure due to renal hemosiderosis in a patient with paroxysmal nocturnal hemoglobinuria. Clin Nephrol. 1993; 39(1):28-31. [PMID]
[27] Clark DA, Butler SA, Braren V, Hartmann RC, Jenkins DE Jr. The kidneys in paroxysmal nocturnal hemoglobinuria. Blood. 1981; 57(1):83-9. [PMID]
[28] Riley AL, Ryan LM, Roth DA. Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria. Am J Med. 1977; 62(1):125-9. [DOI:10.1016/0002-9343(77)90357-6]
[29] Hsiao PJ, Wang SC, Wen MC, Diang LK, Lin SH. Fanconi syndrome and CKD in a patient with paroxysmal nocturnal hemoglobinuria and hemosiderosis. Am J Kidney Dis. 2010; 55(1):e1-5. [DOI:10.1053/j.ajkd.2009.07.022] [PMID]
[30] Mathieu D, Rahmouni A, Villeneuve P, Anglade MC, Rochant H, Vasile N. Impact of magnetic resonance imaging on the diagnosis of abdominal complications of paroxysmal nocturnal hemoglobin ria. Blood. 1995; 85(11):3283-8. [DOI:10.1182/blood.V85.11.3283.bloodjournal85113283] [PMID]
[31] Mulopulos GP, Turner DA, Schwartz MM, Murakami ME, Clark JW. MRI of the kidneys in paroxysmal nocturnal hemoglobinuria. AJR Am J Roentgenol. 1986; 146(1):51-2. [DOI:10.2214/ajr.146.1.51 ] [PMID]
[32] Nguyen JS, Marinopoulos SS, Ashar BH, Flynn JA. Clinical problem-solving. More than meets the eye. N Engl J Med. 2006; 355(10):1048-52. [DOI:10.1056/NEJMcps044359] [PMID]
[33] Rimola J, Martín J, Puig J, Darnell A, Massuet A. The kidney in paroxysmal nocturnal haemoglobinuria: MRI findings. Br J Radiol. 2004; 77(923):953-6. [DOI:10.1259/bjr/51760601] [PMID]
[34] Suzukawa K, Ninomiya H, Mitsuhashi S, Anno I, Nagasawa T, Abe T. Demonstration of the deposition of hemosiderin in the kidneys of patients with paroxysmal nocturnal hemoglobinuria by magnetic resonance imaging. Intern Med. 1993; 32(9):686-90. [DOI:10.2169/internalmedicine.32.686] [PMID]
[35] Tanaka YO, Anno I, Itai Y, Abe T. Paroxysmal nocturnal hemoglobinuria: MR findings. J Comput Assisted Tomogr. 1993; 17(5):749-53. [DOI:10.1097/00004728-199309000-00016] [PMID]
[36] Nath KA, Vercellotti GM, Grande JP, Miyoshi H, Paya CV, Manivel JC, et al. Heme protein-induced chronic renal inflammation: Suppressive effect of induced heme oxygenase-1. Kidney Int. 2001; 59(1):106-17. [DOI:10.1046/j.1523-1755.2001.00471.x] [PMID]
[37] Hillmen P, Elebute M, Kelly R, Urbano-Ispizua A, Hill A, Rother RP, et al. Long-term effect of the complement inhibitor eculizumab on kidney function in patients with paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2010; 85(8):553-9. [DOI:10.1002/ajh.21757] [PMID]
[38] Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney func-tion-measured and estimated glomerular filtration rate. N Engl J Med. 2006; 354(23):2473-83. [DOI:10.1056/NEJMra054415] [PMID]
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| Issue | Vol 8 No 1/2 (2022) | |
| Section | Original Article(s) | |
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| Paroxysmal Nocturnal Hemoglobinuria Cost Secondary Economic burden Illness | ||
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How to Cite
1.
Dadfar S, Seyedifar M, Roozbahani S, Soleymani F. Economic Burden of Paroxysmal Nocturnal Hemoglobinuria (PNH) and Secondary Problems Caused by PNH. JPPM. 2022;8(1/2):15-23.
