Paroxysmal Nocturnal Hemoglobinuria (PNH)


Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, life-threatening disorder characterized by the premature breakdown of erythrocytes and the release of hemoglobin into urine for excretion.1

Incidence and Prevalence of PNH

Due to its rarity, the exact prevalence and incidence of PNH are unknown.2,3 In the US, PNH has an estimated incidence rate that is 5 to 10 times less than that of aplastic anemia, which is around 0.6 to 6.1 cases per million people.2,4 The estimated prevalence is between 1 and 9 of every 100,000 people.3

The global prevalence of PNH is as high as 15.9 individuals per 1 million people. The annual global incidence of PNH is around 5 to 6 individuals per 1 million people.5,6  

In the United States, researchers estimate the prevalence of monoclonal PNH cases at 3000 individuals and biclonal (or multiclonal) PNH cases at 2 individuals based on the 2010 US Census Bureau. Other estimations for PNH incidence and prevalence in the United States are based on research conducted in the United Kingdom.7 

Studies on PNH Incidence and Prevalence

Researchers collected data between January 1991 and July 2006 in Northern Lincolnshire and North, West, and East Yorkshire in the United Kingdom. The data indicated that 76 patients received a PNH diagnosis during this time period, resulting in an annual incidence of 0.13 per 100,000 people.7,8 

Using this incidence rate plus relevant data on PNH survival, the researchers calculated the estimated 15-year prevalence of PNH at around 1.59 per 100,000 people, resulting in a predicted prevalence of 59 patients throughout these regions in the United Kingdom. These researchers then predicted the prevalence of PNH in the United States at around 4713 total cases based on their prevalence rate in the United Kingdom and 2005 US Census Bureau information.7,8 Based on more recent 2020 US Census Bureau population numbers, the current prevalence of PNH in the United States is estimated to be between 3000 and 6000 individuals.7

Another retrospective study was recently published that detailed PNH epidemiology in the United States. It suggests that the prevalence of PNH in the United States between 2016 and 2017 ranged from 12 to 13 cases per 1 million people with an estimated incidence of 5.7 per 1 million person-years over the 3.5-year study period.9

Read more about PNH diagnosis

Geographical Factors of PNH

Research suggests that PNH occurs with higher frequency in Southeast and Eastern Asia.3,10 Aplastic anemia also occurs at greater rates among individuals in this region.6 Aplastic anemia is a risk factor for developing PNH.7

Age Factors of PNH

Paroxysmal nocturnal hemoglobinuria can develop at any age.2,3 Medical records indicate that the onset of PNH can vary, occurring in children as young as 2 years of age as well as in adults in their 80s.2

Most patients with PNH are initially diagnosed in their 30s.10 Most patients with PNH fall between 30 and 40 years of age.5 One study in 2012 calculated a median age of 42 years in the 1610 patients with PNH listed in the International PNH Registry2,5,11; ages ranged from 3 to 99 years in this study.5,11

Read more about PNH prognosis

Sex Factors of PNH

Most sources indicate that men and women are equally affected by PNH.2,3,7 Some research suggests that there is a slight female preponderance.10,12,13 

The suggested explanation for this slight female predisposition (despite an X-linked chromosomal genetic mutation as the cause of the condition) is due to the mutational defect occurring in somatic (clonal) hematopoietic stem cells instead of germline cells. Men only have one X chromosome. Although women have two X chromosomes, they express only one X chromosome due to inactivation of the duplicate X chromosome, but there exists a slightly greater chance of one of these two X chromosomes having the somatic mutation.5

Read more about PNH genetics

Race/Ethnicity Factors of PNH

The occurrence of PNH has no evident ethnic/racial predilection. Although PNH does not affect any particular ethnicity or race, complications due to PNH occur more frequently in certain ethnic groups.5,14  

Studies on Race and Ethnicity Factors of PNH

According to one study in the United States analyzing 64 patients of varying ethnicities diagnosed with PNH, thromboembolic events occurred more frequently in Black (73%) and Latin American patients (50%) with PNH than in patients of other ethnicities with PNH.2,5,15   

Another study conducted at Duke University analyzed the clinical course and disease manifestations of PNH in 176 American patients compared with those of 209 Japanese patients. They noted that White American patients tended to be younger and presented with more classical PNH symptoms such as infection, hemoglobinuria, and thrombosis. In contrast, the Japanese patients with PNH tended to be older with increased bone marrow aplasia and smaller PNH clones. Secondary to the increased incidence of thrombosis, the American patients with PNH demonstrated increased mortality rates.2,5,16

Read more about PNH complications

References

  1. Besa EC. Paroxysmal nocturnal hemoglobinuria: practice essentials. Medscape. Updated May 20, 2021. Accessed November 21, 2022.
  2. Besa EC. Paroxysmal nocturnal hemoglobinuria: epidemiology. Medscape. Updated May 20, 2021. Accessed November 21, 2022.
  3. Paroxysmal nocturnal hemoglobinuria. Orphanet. Accessed November 21, 2022.
  4. Bakhshi S. Aplastic anemia: Practice essentials. Medscape. Updated January 29, 2021. Accessed November 21, 2022.
  5. Shah N, Bhatt H. Paroxysmal nocturnal hemoglobinuria. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated August 1, 2022. Accessed November 21, 2022.
  6. Farooq Q, Saleem MW, Khan ZU, Hadi N. Paroxysmal nocturnal hemoglobinuria: a diagnostic “zero-sum-game”. Cureus. 2020;12(12):e11956. doi:10.7759/cureus.11956
  7. Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM. Paroxysmal nocturnal hemoglobinuria: role of the complement system, pathogenesis, and pathophysiology. J Manag Care Spec Pharm. 2020;26(12-b Suppl):S3-S8. doi:10.18553/jmcp.2020.26.12-b.s3
  8. Hill A, Platts PJ, Smith A, 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
  9. Jalbert JJ, Chaudhari U, Zhang H, Weyne J, Shammo JM. Epidemiology of PNH and real-world treatment patterns following an incident PNH diagnosis in the US. Blood. 2019;134(Supplement_1):3407. doi:10.1182/blood-2019-125867
  10. Paroxysmal nocturnal hemoglobinuria. National Organization for Rare Disorders (NORD). Accessed November 21, 2022.
  11. Schrezenmeier H, Muus P, Socié G, et al. Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry. Haematologica. 2014;99(5):922-929. doi:10.3324/haematol.2013.093161
  12. Patriquin C, Leber B. Increased eculizumab requirements during pregnancy in a patient with paroxysmal nocturnal hemoglobinuria: case report and review of the literature. Clin Case Rep. 2015;3(2):88-91. doi:10.1002/ccr3.161
  13. de Latour RP, Mary JY, Salanoubat C, et al; French Society of Hematology; French Association of Young Hematologists. Paroxysmal nocturnal hemoglobinuria: natural history of disease subcategories. Blood. 2008;112(8):3099-3106. doi:10.1182/blood-2008-01-133918
  14. Brodsky RA. Clinical manifestations and diagnosis of paroxysmal nocturnal hemoglobinuria. UpToDate. Accessed November 21, 2022.
  15. 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
  16. Nishimura JI, 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;83(3):193-207. doi:10.1097/01.md.0000126763.68170.46

Reviewed by Harshi Dhingra, MD, on 11/15/2022.

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