About PNH

PNH: A progressive, destructive, and life-threatening disease1

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder caused by an acquired mutation in the phosphatidylinositol glycan class A (PIG-A gene). All resulting cell lines from these PNH marrow clones lack key, naturally occurring terminal complement inhibitors on the cell surface. This renders them vulnerable to constant attack and lysis by the terminal complement complex (TCC), also known as C5b-9 or the membrane attack complex (MAC). The result is chronic, intravascular hemolysis, and is life-threatening.2

PNH can cause thrombosis, end-organ damage, and early mortality

35% of PNH patients die within 5 years of diagnosis despite best historical care1
  • Thrombosis and renal failure are leading causes of death1,3
  • PNH may be diagnosed at any age; median age is in the early 30s3
  • Diagnosis typically delayed from 1 to more than 10 years4
  • More than three-fourths of patients with PNH do not present with hemoglobinuria at time of diagnosis5
  • In PNH, chronic complement-mediated hemolysis can lead to devastating consequences6,7

PNH is a disease of chronic uncontrolled complement activation8

Consequences of chronic, uncontrolled complement activation9-12
  • Complement is activated to allow rapid first-line immune responses13
  • Insufficient regulation of the complement cascade can have highly destructive effects13
  • In PNH, the deficiency of complement inhibitors leads to chronic, uncontrolled complement activation, resulting in chronic intravascular hemolysis and granulocyte and platelet activation6,9,14-17

Historical care for PNH

Historically, there have been few options for care of patients with PNH. Palliative therapies include blood transfusions, corticosteroids, anticoagulants, androgen therapy, supplements such as folic acid and iron, and bone marrow transplantation, but patients with PNH suffer high rates of mortality despite any of these supportive therapy options. Characterization of the role of complement in the pathophysiology of PNH has led to major advances in caring for patients with PNH using monoclonal antibody therapy.5,18

High-Risk Patient Groups

Early diagnosis can positively impact long-term patient outcomes. Learn about ICCS and IPIG recommendations for who should be tested for PNH.

Clinical Assessment for Risks of Early Mortality

For more information about the important role of a full clinical assessment for your patient with PNH, download the Clinical Assessment for Risks of Early Mortality.


PNH has been called “the most vicious acquired thrombophilic state known in medicine”.19 Learn which common symptoms are associated with an increased risk of thromboembolism in a patient diagnosed with PNH.

References: 1. Hillmen P, Lewis SM, Bessler M, et al. N Engl J Med. 1995;333:1253-1258. 2. Risitano AM. Adv Exp Med Biol. 2013;735:155-172. 3. Socié G, Mary J-Y, de Gramont A, et al; for the French Society of Haematology. Lancet. 1996;348:573-577. 4. Dacie JV, Lewis SM. Ser Haematol. 1972;5:3-23. 5. Parker C, Omine M, Richards S, et al; for International PNH Interest Group. Blood. 2005;106:3699-3709. 6. Rachidi S, Musallam KM, Taher AT. Eur J Intern Med. 2010;21:260-267. 7. Borowitz MJ, Craig FE, DiGiuseppe JA, et al; for Clinical Cytometry Society. Cytometry Part B. 2010;78B:211-230. 8. Urbano-Ispizua A, Schrezenmeier H, Muus P, et al. An International PNH Registry study. Blood. 2011;118: Abstract 2102. 9. Walport MJ. N Engl J Med. 2001;344:1058-1066. 10. Walport MJ. N Engl J Med. 2001;344:1140-1144. 11. Noris M, Remuzzi G. N Engl J Med. 2009;361:1676-1687. 12. Rosse WF, Hillmen P, Schreiber AD. Hematology Am Soc Hematol Educ Program. 2004:48-62. 13. Ricklin D, Lambris JD. Nat Biotechnol. 2007;25:1265-1275. 14. Rother RP, Bell L, Hillmen P, et al. JAMA. 2005;293:1653-1662. 15. Bessler M, Schrezenmeier H, Maciejewski JP, et al. Blood. 2007;110: Abstract 840. 16. Nishimura J-I, Kanakura Y, Ware RE, et al. Medicine. 2004;83:193-207. 17. Lee JW, Jang JH, Lee JH, et al. Haematologica. 2010;95(s2):205-206. 18. Moyo VM, Mukhina GL, Garrett ES, et al. Br J Haematol. 2004;126:133-138. 19. Hill A, Kelly R, Hillmen P. Blood. 2013;121:4985-4996.