Paroxysmal Nocturnal Hemoglobinuria Questions & Answers

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7. Brodsky RA. Complement in hemolytic anemia. Blood. 2015 Nov 26. 126 (22):2459-65. [QxMD MEDLINE Link]. [Full Text].

8. Nagarajan S, Brodsky RA, Young NS, Medof ME. Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia. Blood. 1995 Dec 15. 86(12):4656-61. [QxMD MEDLINE Link]. [Full Text].

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11. Young NS. Hematopoietic cell destruction by immune mechanisms in acquired aplastic anemia. Semin Hematol. 2000 Jan. 37(1):3-14. [QxMD MEDLINE Link].

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13. Griffin M, Munir T. Management of thrombosis in paroxysmal nocturnal hemoglobinuria: a clinician's guide. Ther Adv Hematol. 2017 Mar. 8 (3):119-126. [QxMD MEDLINE Link]. [Full Text].

14. Rosse W. A new way to prevent thrombosis. Blood. 2007. 110:3821.

15. Shen W, Clemente MJ, Hosono N, Yoshida K, Przychodzen B, Yoshizato T, et al. Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria. J Clin Invest. 2014 Oct 1. 124(10):4529-38. [QxMD MEDLINE Link]. [Full Text].

16. Socié 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 Sep. 46 (9):1044-53. [QxMD MEDLINE Link].

17. 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 Jun. 103 (6):649-54. [QxMD MEDLINE Link].

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19. Araten DJ, Thaler HT, Luzzatto L. High incidence of thrombosis in African-American and Latin-American patients with Paroxysmal Nocturnal Haemoglobinuria. Thromb Haemost. 2005 Jan. 93(1):88-91. [QxMD MEDLINE Link].

20. Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Leaverton PE, Shapiro S, et al. The epidemiology of aplastic anemia in Thailand. Blood. 2006 Feb 15. 107 (4):1299-307. [QxMD MEDLINE Link].

21. Young NS, Kaufman DW. The epidemiology of acquired aplastic anemia. Haematologica. 2008 Apr. 93 (4):489-92. [QxMD MEDLINE Link]. [Full Text].

22. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995 Nov 9. 333(19):1253-8. [QxMD MEDLINE Link].

23. 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 May. 99(5):922-9. [QxMD MEDLINE Link]. [Full Text].

24. Socie G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996 Aug 31. 348(9027):573-7. [QxMD MEDLINE Link].

25. Nishimura J, Kanakura Y, Ware RE, et al. Clinical course and flow cytometric analysis of paroxysmal nocturnal hemoglobinuria in the United States and Japan. Medicine (Baltimore). 2004 May. 83(3):193-207. [QxMD MEDLINE Link].

26. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005 Dec 1. 106(12):3699-709. [QxMD MEDLINE Link]. [Full Text].

27. Kim JS, Jang JH, Yoon SS, Lee JH, Kim YK, Jo DY, et al. Distinct subgroups of paroxysmal nocturnal hemoglobinuria (PNH) with cytopenia: results from South Korean National PNH Registry. Ann Hematol. 2015 Sep 29. [QxMD MEDLINE Link].

28. Dulau-Florea A, Maric I, Calvo KR, Braylan RC. Detection of paroxysmal nocturnal hemoglobinuria (PNH) in bone marrow aspirates^☆. Semin Hematol. 2019 Jan. 56 (1):65-68. [QxMD MEDLINE Link].

29. 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 Jul. 78(4):211-30. [QxMD MEDLINE Link].

30. Rosse WF, Dacie JV. The role of complement in the sensitivity of the paroxysmal nocturnal haemoglobinuria red cell to immune lysis. Bibl Haematol. 1965. 23:11-8. [QxMD MEDLINE Link].

31. Rosse WF, Dacie JV. Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. I. The sensitivity of PNH red cells to lysis by complement and specific antibody. J Clin Invest. 1966 May. 45(5):736-48. [QxMD MEDLINE Link]. [Full Text].

32. Rosse WF, Dacie JV. Immune lysis of normal human and paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. II. The role of complement components in the increased sensitivity of PNH red cells to immune lysis. J Clin Invest. 1966 May. 45(5):749-57. [QxMD MEDLINE Link]. [Full Text].

33. Brodsky RA. Stem cell transplantation for paroxysmal nocturnal hemoglobinuria. Haematologica. 2010 Jun. 95(6):855-6. [QxMD MEDLINE Link]. [Full Text].

34. Cooper JP, Farah RJ, Stevenson PA, Gooley TA, Storb R, Scott BL. Hematopoietic Cell Transplantation for Paroxysmal Nocturnal Hemoglobinuria in the Age of Eculizumab. Biol Blood Marrow Transplant. 2019 Jul. 25 (7):1331-1339. [QxMD MEDLINE Link]. [Full Text].

35. Ebenbichler CF, Wurzner R, Sandhofer AD, Niederwieser D, Dierich MP, Patsch JR. Anti-thymocyte globulin treatment of a patient for paroxysmal nocturnal haemoglobinuria-aplastic anaemia syndrome: complement activation and transient decrease of the PNH clone. Immunobiology. 1996-1997. 196(5):513-21. [QxMD MEDLINE Link].

36. Röth A, Nishimura JI, Nagy Z, et al. The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria. Blood. 2020 Mar 19. 135 (12):912-920. [QxMD MEDLINE Link]. [Full Text].

37. Risitano AM, Marotta S. Toward complement inhibition 2.0: Next generation anticomplement agents for paroxysmal nocturnal hemoglobinuria. Am J Hematol. 2018 Aug. 93 (4):564-577. [QxMD MEDLINE Link].

38. Yuan X, Gavriilaki E, Thanassi JA, Yang G, Baines AC, Podos SD, et al. Small-molecule factor D inhibitors selectively block the alternative pathway of complement in paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Haematologica. 2017 Mar. 102 (3):466-475. [QxMD MEDLINE Link]. [Full Text].

39. Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, et al. Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Blood Adv. 2022 Aug 9. 6 (15):4450-4460. [QxMD MEDLINE Link].

40. Risitano AM, Röth A, Soret J, Frieri C, de Fontbrune FS, Marano L, et al. Addition of iptacopan, an oral factor B inhibitor, to eculizumab in patients with paroxysmal nocturnal haemoglobinuria and active haemolysis: an open-label, single-arm, phase 2, proof-of-concept trial. Lancet Haematol. 2021 May. 8 (5):e344-e354. [QxMD MEDLINE Link].

41. Bomback AS, Kavanagh D, Vivarelli M, Meier M, Wang Y, Webb NJA, et al. Alternative Complement Pathway Inhibition With Iptacopan for the Treatment of C3 Glomerulopathy-Study Design of the APPEAR-C3G Trial. Kidney Int Rep. 2022 Oct. 7 (10):2150-2159. [QxMD MEDLINE Link].

42. Risitano AM, Kulasekararaj AG, Lee JW, Maciejewski JP, Notaro R, Brodsky R, et al. Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria. Haematologica. 2021 Dec 1. 106 (12):3188-3197. [QxMD MEDLINE Link]. [Full Text].

43. Kulasekararaj AG, Risitano AM, Maciejewski JP, Notaro R, Browett P, Lee JW, et al. Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab. Blood. 2021 Nov 18. 138 (20):1928-1938. [QxMD MEDLINE Link]. [Full Text].

44. Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Füreder W, et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019 Feb 7. 133 (6):530-539. [QxMD MEDLINE Link]. [Full Text].

45. Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, et al. Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. Blood. 2019 Feb 7. 133 (6):540-549. [QxMD MEDLINE Link]. [Full Text].

46. Hillmen P, Hall C, Marsh JC, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004 Feb 5. 350(6):552-9. [QxMD MEDLINE Link].

47. Hill A, Hillmen P, Richards SJ, et al. Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria. Blood. 2005 Oct 1. 106(7):2559-65. [QxMD MEDLINE Link].

48. Sicre de Fontbrune F, Peffault de Latour R. Ten Years of Clinical Experience With Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria. Semin Hematol. 2018 Jul. 55 (3):124-129. [QxMD MEDLINE Link].

49. Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011 Jun 23. 117(25):6786-92. [QxMD MEDLINE Link].

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51. Alashkar F, Vance C, Herich-Terhürne D, Preising N, Dührsen U, Röth A. Serologic response to meningococcal vaccination in patients with paroxysmal nocturnal hemoglobinuria (PNH) chronically treated with the terminal complement inhibitor eculizumab. Ann Hematol. 2017 Apr. 96 (4):589-596. [QxMD MEDLINE Link].

52. Kelly RJ, Hill A, Arnold LM, Brooksbank GL, Richards SJ, Cullen M. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011 Jun 23. 117(25):6786-92. [QxMD MEDLINE Link].

53. Peipert JD, Kulasekararaj AG, Gaya A, Langemeijer SMC, Yount S, Gonzalez-Fernandez FA, et al. Patient preferences and quality of life implications of ravulizumab (every 8 weeks) and eculizumab (every 2 weeks) for the treatment of paroxysmal nocturnal hemoglobinuria. PLoS One. 2020. 15 (9):e0237497. [QxMD MEDLINE Link]. [Full Text].

54. Brodsky RA, Peffault de Latour R, Rottinghaus ST, Röth A, Risitano AM, Weitz IC, et al. Characterization of breakthrough hemolysis events observed in the phase 3 randomized studies of ravulizumab versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria. Haematologica. 2020 Jan 16. [QxMD MEDLINE Link]. [Full Text].

55. Lee JW, Kulasekararaj AG. Ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Expert Opin Biol Ther. 2020 Mar. 20 (3):227-237. [QxMD MEDLINE Link].

56. Tomazos I, Sierra JR, Johnston KM, Cheung A, Brodsky RA, Weitz IC. Cost burden of breakthrough hemolysis in patients with paroxysmal nocturnal hemoglobinuria receiving ravulizumab versus eculizumab. Hematology. 2020 Dec. 25 (1):327-334. [QxMD MEDLINE Link]. [Full Text].

57. O'Connell T, Buessing M, Johnson S, Tu L, Thomas SK, Tomazos I. Cost-Utility Analysis of Ravulizumab Compared with Eculizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria. Pharmacoeconomics. 2020 Sep. 38 (9):981-994. [QxMD MEDLINE Link].

58. Peipert JD, Kulasekararaj AG, Gaya A, Langemeijer SMC, Yount S, Gonzalez-Fernandez FA, et al. Patient preferences and quality of life implications of ravulizumab (every 8 weeks) and eculizumab (every 2 weeks) for the treatment of paroxysmal nocturnal hemoglobinuria. PLoS One. 2020. 15 (9):e0237497. [QxMD MEDLINE Link]. [Full Text].

59. FDA approves ravulizumab-cwvz for paroxysmal nocturnal hemoglobinuria. U.S. Food & Drug Administration. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ravulizumab-cwvz-paroxysmal-nocturnal-hemoglobinuria. December 26, 2018; Accessed: April 22, 2023.

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64. Wong R, Fishman J, Wilson K, Yeh M, Al-Adhami M, Zion A, et al. Comparative Effectiveness of Pegcetacoplan Versus Ravulizumab and Eculizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria: A Matching-Adjusted Indirect Comparison. Adv Ther. 2023 Apr. 40 (4):1571-1589. [QxMD MEDLINE Link]. [Full Text].

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66. Kuo GP, Brodsky RA, Kim HS. Catheter-directed thrombolysis and thrombectomy for the Budd-Chiari syndrome in paroxysmal nocturnal hemoglobinuria in three patients. J Vasc Interv Radiol. 2006 Feb. 17 (2 Pt 1):383-7. [QxMD MEDLINE Link].

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Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, The Society of Federal Health Professionals (AMSUS), International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Sara J Grethlein, MD, MBA, FACP Executive Medical Director and Medical Oncologist, Swedish Cancer Institute

Sara J Grethlein, MD, MBA, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Women's Association, American Society of Clinical Oncology, American Society of Hematology, Gold Humanism Honor Society, Leukemia and Lymphoma Society

Disclosure: Nothing to disclose.

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