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Paroxysmal nocturnal hemoglobinuria(PNH)

MedGen UID:
7471
Concept ID:
C0024790
Disease or Syndrome
Synonyms: Acquired paroxysmal nocturnal hemoglobinuria; PNH
SNOMED CT: Paroxysmal nocturnal hemoglobinuria (1963002); Marchiafava-Micheli syndrome (1963002); PNH - paroxysmal nocturnal hemoglobinuria (1963002)
Modes of inheritance:
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
HPO: HP:0004818
Monarch Initiative: MONDO:0100244
OMIM®: 311770
OMIM® Phenotypic series: PS300818
Orphanet: ORPHA447

Definition

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired (not inherited) disorder that leads to the premature death and impaired production of blood cells. The disorder affects red blood cells (erythrocytes), which carry oxygen; white blood cells (leukocytes), which protect the body from infections; and platelets (thrombocytes), which are involved in blood clotting. PNH can occur at any age, although it is most often diagnosed in young adulthood.

People with PNH have sudden, recurring episodes of symptoms (paroxysmal symptoms), which may be triggered by stresses on the body, such as infections or physical exertion. During these episodes, red blood cells are broken down earlier than they should be (hemolysis). Affected individuals may pass dark-colored urine because of the presence of hemoglobin, the oxygen-carrying protein in blood. The abnormal presence of hemoglobin in the urine is called hemoglobinuria. In many, but not all cases, hemoglobinuria is most noticeable early in the morning, upon passing urine that has accumulated in the bladder during the night (nocturnal).

The premature breakdown of red blood cells results in a shortage of these cells in the blood (hemolytic anemia), which can cause signs and symptoms such as fatigue, weakness, abnormally pale skin (pallor), shortness of breath, and an increased heart rate (tachycardia). People with PNH may also be prone to infections because of a shortage of white blood cells (leukopenia).

Abnormal platelets associated with PNH can cause problems in the blood clotting process. As a result, people with this disorder may experience abnormal blood clotting (thrombosis), especially in large abdominal veins; or, less often, episodes of severe bleeding (hemorrhage).

Individuals with PNH are at increased risk of developing cancer in blood-forming cells (leukemia). In some cases, people who have or have been treated for another blood disease called aplastic anemia may develop PNH. In a small number of affected individuals, the signs and symptoms of PNH disappear on their own.

A very rare form of PNH involves abnormal inflammation in addition to the typical features described above. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). In people with this rare form of PNH, the immune response is turned on (activated) abnormally and can cause recurrent aseptic meningitis (which is inflammation of the membranes surrounding the brain and spinal cord that is not related to infection); a red, itchy rash (known as hives or urticaria); joint pain (arthralgia); or inflammatory bowel disease. The inflammatory disorders usually begin earlier than the blood cell problems. [from MedlinePlus Genetics]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVParoxysmal nocturnal hemoglobinuria
Follow this link to review classifications for Paroxysmal nocturnal hemoglobinuria in Orphanet.

Conditions with this feature

Primary CD59 deficiency
MedGen UID:
393582
Concept ID:
C2676767
Disease or Syndrome
CD59-mediated hemolytic anemia with immune-mediated polyneuropathy is an autosomal recessive disorder characterized by infantile onset of a relapsing-remitting polyneuropathy, often exacerbated by infection, and manifest as hypotonia, limb muscle weakness, and hyporeflexia. Immunosuppressive treatment may result in some clinical improvement (summary by Nevo et al., 2013).
Paroxysmal nocturnal hemoglobinuria 1
MedGen UID:
813000
Concept ID:
C3806670
Disease or Syndrome
Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired hemolytic anemia that often manifests with hemoglobinuria, abdominal pain, smooth muscle dystonias, fatigue, and thrombosis. The disease results from the expansion of hematopoietic stem cells harboring a mutation in the PIGA gene, which encodes a protein required for the biosynthesis of glycosylphosphatidylinositol (GPI), a lipid moiety that attaches dozens of proteins to the cell surface. Thus, PNH cells are deficient in cell surface GPI-anchored proteins. This deficiency on erythrocytes leads to intravascular hemolysis, since certain GPI-anchored proteins (i.e., CD55 (125240) and CD59 (107271)) normally function as complement regulators. Free hemoglobin released from intravascular hemolysis leads to circulating nitrous oxide depletion and is responsible for many of the clinical manifestations of PNH, including fatigue, erectile dysfunction, esophageal spasm, and thrombosis (review by Brodsky, 2008). Genetic Heterogeneity of Paroxysmal Nocturnal Hemoglobinuria See also PNH2 (615399), which may be caused by germline and somatic mutation in the PIGT gene (610272) on chromosome 20q13.
Paroxysmal nocturnal hemoglobinuria 2
MedGen UID:
815699
Concept ID:
C3809369
Disease or Syndrome
Any paroxysmal nocturnal hemoglobinuria in which the cause of the disease is a mutation in the PIGT gene.

Professional guidelines

PubMed

Bravo-Perez C, Guarnera L, Williams ND, Visconte V
Medicina (Kaunas) 2023 Sep 6;59(9) doi: 10.3390/medicina59091612. PMID: 37763731Free PMC Article
Szlendak U, Budziszewska B, Spychalska J, Drozd-Sokołowska J, Patkowska E, Nowak J
Pol Arch Intern Med 2022 Jun 29;132(6) Epub 2022 Jun 6 doi: 10.20452/pamw.16271. PMID: 35699625
Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socié G; International PNH Interest Group
Blood 2005 Dec 1;106(12):3699-709. Epub 2005 Jul 28 doi: 10.1182/blood-2005-04-1717. PMID: 16051736Free PMC Article

Curated

Orphanet, Paroxysmal Nocturnal Haemoglobinuria, 2008

Recent clinical studies

Etiology

Peffault de Latour R, Röth A, Kulasekararaj AG, Han B, Scheinberg P, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Wong Lee Lee L, Yap ES, Sicre de Fontbrune F, Marano L, Alashkar F, Gandhi S, Trikha R, Yang C, Liu H, Kelly RJ, Höchsmann B, Kerloeguen C, Banerjee P, Levitch R, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, Risitano AM
N Engl J Med 2024 Mar 14;390(11):994-1008. doi: 10.1056/NEJMoa2308695. PMID: 38477987
Colden MA, Kumar S, Munkhbileg B, Babushok DV
Front Immunol 2021;12:830172. Epub 2022 Jan 28 doi: 10.3389/fimmu.2021.830172. PMID: 35154088Free PMC Article
Hillmen P, Szer J, Weitz I, Röth A, Höchsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, Peffault de Latour R
N Engl J Med 2021 Mar 18;384(11):1028-1037. doi: 10.1056/NEJMoa2029073. PMID: 33730455
Brodsky RA
Blood 2021 Mar 11;137(10):1304-1309. doi: 10.1182/blood.2019003812. PMID: 33512400Free PMC Article
Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socié G; International PNH Interest Group
Blood 2005 Dec 1;106(12):3699-709. Epub 2005 Jul 28 doi: 10.1182/blood-2005-04-1717. PMID: 16051736Free PMC Article

Diagnosis

Szlendak U, Budziszewska B, Spychalska J, Drozd-Sokołowska J, Patkowska E, Nowak J
Pol Arch Intern Med 2022 Jun 29;132(6) Epub 2022 Jun 6 doi: 10.20452/pamw.16271. PMID: 35699625
Brodsky RA
Blood 2021 Mar 11;137(10):1304-1309. doi: 10.1182/blood.2019003812. PMID: 33512400Free PMC Article
Daughety MM, DeLoughery TG
Med Clin North Am 2017 Mar;101(2):417-429. Epub 2016 Dec 10 doi: 10.1016/j.mcna.2016.09.011. PMID: 28189179
Brodsky RA
Blood 2014 Oct 30;124(18):2804-11. Epub 2014 Sep 18 doi: 10.1182/blood-2014-02-522128. PMID: 25237200Free PMC Article
Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socié G; International PNH Interest Group
Blood 2005 Dec 1;106(12):3699-709. Epub 2005 Jul 28 doi: 10.1182/blood-2005-04-1717. PMID: 16051736Free PMC Article

Therapy

Peffault de Latour R, Röth A, Kulasekararaj AG, Han B, Scheinberg P, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Wong Lee Lee L, Yap ES, Sicre de Fontbrune F, Marano L, Alashkar F, Gandhi S, Trikha R, Yang C, Liu H, Kelly RJ, Höchsmann B, Kerloeguen C, Banerjee P, Levitch R, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, Risitano AM
N Engl J Med 2024 Mar 14;390(11):994-1008. doi: 10.1056/NEJMoa2308695. PMID: 38477987
Babushok DV
Hematology Am Soc Hematol Educ Program 2021 Dec 10;2021(1):143-152. doi: 10.1182/hematology.2021000245. PMID: 34889408Free PMC Article
Hillmen P, Szer J, Weitz I, Röth A, Höchsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, Peffault de Latour R
N Engl J Med 2021 Mar 18;384(11):1028-1037. doi: 10.1056/NEJMoa2029073. PMID: 33730455
Brodsky RA
Blood 2021 Mar 11;137(10):1304-1309. doi: 10.1182/blood.2019003812. PMID: 33512400Free PMC Article
Daughety MM, DeLoughery TG
Med Clin North Am 2017 Mar;101(2):417-429. Epub 2016 Dec 10 doi: 10.1016/j.mcna.2016.09.011. PMID: 28189179

Prognosis

Duval A, Frémeaux-Bacchi V
Am J Hematol 2023 May;98 Suppl 4:S5-S19. doi: 10.1002/ajh.26855. PMID: 36688486
Szlendak U, Budziszewska B, Spychalska J, Drozd-Sokołowska J, Patkowska E, Nowak J
Pol Arch Intern Med 2022 Jun 29;132(6) Epub 2022 Jun 6 doi: 10.20452/pamw.16271. PMID: 35699625
Sun L, Babushok DV
Blood 2020 Jul 2;136(1):36-49. doi: 10.1182/blood.2019000940. PMID: 32430502Free PMC Article
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Füreder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A
Blood 2019 Feb 7;133(6):530-539. Epub 2018 Dec 3 doi: 10.1182/blood-2018-09-876136. PMID: 30510080Free PMC Article
Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, Gaya A, Lee JW, Gutierrez EO, Piatek CI, Szer J, Risitano A, Nakao S, Bachman E, Shafner L, Damokosh AI, Ortiz S, Röth A, Peffault de Latour R
Blood 2019 Feb 7;133(6):540-549. Epub 2018 Dec 3 doi: 10.1182/blood-2018-09-876805. PMID: 30510079Free PMC Article

Clinical prediction guides

Risitano AM, Frieri C, Urciuoli E, Marano L
Immunol Rev 2023 Jan;313(1):262-278. Epub 2022 Sep 15 doi: 10.1111/imr.13137. PMID: 36110036Free PMC Article
Hillmen P, Szer J, Weitz I, Röth A, Höchsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, Peffault de Latour R
N Engl J Med 2021 Mar 18;384(11):1028-1037. doi: 10.1056/NEJMoa2029073. PMID: 33730455
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Füreder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A
Blood 2019 Feb 7;133(6):530-539. Epub 2018 Dec 3 doi: 10.1182/blood-2018-09-876136. PMID: 30510080Free PMC Article
Hillmen P, Young NS, Schubert J, Brodsky RA, Socié G, Muus P, Röth A, Szer J, Elebute MO, Nakamura R, Browne P, Risitano AM, Hill A, Schrezenmeier H, Fu CL, Maciejewski J, Rollins SA, Mojcik CF, Rother RP, Luzzatto L
N Engl J Med 2006 Sep 21;355(12):1233-43. doi: 10.1056/NEJMoa061648. PMID: 16990386
Frank MM
Pediatr Clin North Am 2000 Dec;47(6):1339-54. doi: 10.1016/s0031-3955(05)70274-1. PMID: 11130999

Recent systematic reviews

Muvaffak E, Mokresh ME, Varda A, Lakmoush M, Ilter MK
Expert Rev Hematol 2024 Nov;17(11):819-831. Epub 2024 Oct 28 doi: 10.1080/17474086.2024.2422558. PMID: 39453029
Bodó I, Amine I, Boban A, Bumbea H, Kulagin A, Lukina E, Piekarska A, Zupan IP, Sokol J, Windyga J, Cermak J
Adv Ther 2023 Jun;40(6):2752-2772. Epub 2023 Apr 18 doi: 10.1007/s12325-023-02510-4. PMID: 37072660Free PMC Article
Zhou S, Dong X, Chen C, Ma L, Wu Y, Zhou Y, Cui Y
J Pediatr Hematol Oncol 2021 Aug 1;43(6):203-210. doi: 10.1097/MPH.0000000000002178. PMID: 33902068
Garred P, Tenner AJ, Mollnes TE
Pharmacol Rev 2021 Apr;73(2):792-827. doi: 10.1124/pharmrev.120.000072. PMID: 33687995Free PMC Article
Martí-Carvajal AJ, Anand V, Cardona AF, Solà I
Cochrane Database Syst Rev 2014 Oct 30;(10):CD010340. doi: 10.1002/14651858.CD010340.pub2. PMID: 25356860

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