Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired,[1] life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. There is ongoing research into other key features of the disease, such as the high incidence of venous blood clot formation.[2] Research suggests that PNH thrombosis (a blood clot) is caused by both the absence of GPI-anchored complement regulatory proteins (CD55 and CD59) on PNH platelets and the excessive consumption of nitric oxide (NO).[3]
PNH is the only hemolytic anemia caused by an acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol or GPI) leading to the absence of protective exterior surface proteins that normally attach via a GPI anchor.[4] It may develop on its own ("primary PNH") or in the context of other bone marrow disorders such as aplastic anemia ("secondary PNH"). Only a minority of affected people have the telltale red urine in the morning that originally gave the condition its name.[5]
Allogeneic bone marrow transplantation is the only cure, but has significant rates of additional medical problems and death.[6] The monoclonal antibody eculizumab reduces the need for blood transfusions and improves quality of life for those affected by PNH.[6] Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to the extent that it may be equivalent to that of the general population.[7] Eculizumab costs at least US$440,000 for a single year of treatment and has been reported as one of the world's most expensive drugs.[8][9][10]
^Luzzatto L (August 2013). "PNH from mutations of another PIG gene". Blood. 122 (7): 1099–100. doi:10.1182/blood-2013-06-508556. PMID 23950173.
^Parker CJ (May 2012). "Paroxysmal nocturnal hemoglobinuria". Current Opinion in Hematology. 19 (3): 141–8. doi:10.1097/MOH.0b013e328351c348. PMID 22395662. S2CID 21266914.
^Brodsky, R. A. (2014a). Paroxysmal nocturnal hemoglobinuria. Blood, 124(18), 2804–2811. https://doi.org/10.1182/blood-2014-02-522128
^Kumar Vinay; Abbas AK; Fausto N; Mitchell RN (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. p. 652. ISBN 978-1-4160-2973-1.
^Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, et al. (December 2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood. 106 (12): 3699–709. doi:10.1182/blood-2005-04-1717. PMC 1895106. PMID 16051736.
^ abBrodsky RA (June 2009). "How I treat paroxysmal nocturnal hemoglobinuria". Blood. 113 (26): 6522–7. doi:10.1182/blood-2009-03-195966. PMC 2710914. PMID 19372253.
^Wong EK, Kavanagh D (January 2018). "Diseases of complement dysregulation-an overview". Seminars in Immunopathology. 40 (1): 49–64. doi:10.1007/s00281-017-0663-8. PMC 5794843. PMID 29327071.
^"Alexion Pharmaceuticals ordered to lower price of $500K a year drug in Canada | CBC News". CBC. Retrieved 2018-11-29.
^"British watchdog wants U.S. biotech Alexion to justify cost of drug". Reuters. March 3, 2014. Retrieved June 6, 2014.
^Martí-Carvajal AJ, Anand V, Cardona AF, Solà I (October 2014). "Eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria". The Cochrane Database of Systematic Reviews. 10 (10): CD010340. doi:10.1002/14651858.CD010340.pub2. PMID 25356860.
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