What Is Paroxysmal Nocturnal Haemoglobinuria

  • Hadiza BelloDoctor of Medicine - MD, All Saints University, Saint Vincent, UK


Paroxysmal nocturnal hemoglobinuria (PNH) is a rare stem cell disease related to the stem cells that help in the formation of blood cells, also known as haematopoietic stem cells (HSC).1-7 HSC diseases arise from blood cells that have not yet formed or matured completely and can become any type of blood cell.1,7 

Although PNH is rare, it affects approximately 15.9 individuals per million worldwide1 and fewer than 1000 cases are reported all over the UK. It is a chronic, debilitating (weakens you over time) disorder that often begins to show symptoms in early adulthood, with the most common age group of diagnosis being individuals in 3rd to 4th decade of life.1,3


Paroxysmal Nocturnal Hemoglobinuria (PNH) is mainly caused by a genetic mutation in a gene called PIGA (phosphatidylinositol glycan class A).1,3 The PIGA gene is responsible for the production of specific proteins on the surface of blood cells that prevent the cells from being attacked by the body’s immune system.1,3,5,7 In the absence of this protective protein, these cells are vulnerable to self-immune system attacks, making them susceptible to destruction, which results in pieces of the broken-down blood cells blocking comparatively smaller blood vessels.1,7

PNH is not an inherited disorder.1 It results from a somatic mutation.1 Somatic mutations occur during an individual’s lifetime and usually in a particular group of cells.8 The PIGA gene mutation affects a group of stem cells in the bone marrow that eventually grow into different types of blood cells that lack these protective proteins on their surface, making them more vulnerable to breakdown.1-8 Furthermore, this process of breakdown may be aggravated by external factors such as stress, surgery, or trauma.1 

This increased breakdown of blood cells can result in excess of normal substances in your bloodstream such as haemoglobin (which would normally be cleared by natural cleaners in your blood).1,7 This excess circulating haemoglobin can be harmful to many vital organs, such as the kidneys when blood is filtered through it and the haemoglobin passes into the urine (thus resulting in dark-coloured pee).1,7 

Symptoms and clinical presentation

The symptoms of PNH can be nonspecific but are often a result of red blood cell destruction (hemolysis) and the other possible complications arising from it. The number of symptoms and their severity may vary widely among individuals. 

Some common symptoms of PNH include:

  1. Dark urine: One of the major symptoms of PNH is the presence of haemoglobin in your urine, which presents as dark-coloured urine that is generally reddish or dark brown in colour.1,7 This happens due to the excess release of haemoglobin from destroyed red blood cells, which cannot keep pace with the body's normal clearing process.1-7 Dark urine is often noticed  in the morning or late at night (nocturnal) during frequent(paroxysmal) trips to the bathroom, thus giving rise to the disease "Paroxysmal Nocturnal Hemoglobinuria".1,7
  2. Fatigue and weakness: This is a common manifestation of anaemia due to the immune system’s destruction of red blood cells.1,5 Anaemia leads to reduced oxygen-carrying capacity in the blood, which results in easy fatiguability, decreased exercise tolerance, and weakness.5,6
  3. Shortness of breath: Another symptom related to anaemia is insufficient delivery of oxygen to tissues and organs of the body. Individuals with PNH may experience shortness of breath, especially during physical activity.1,6
  4. Abdominal pain and swelling: Some cases of PNH may present with abdominal pain and discomfort. This is caused by the enlargement of the liver.3,4,5 Enlargement commonly occurs due to increased blood cell destruction, leading to blockages in the vessels that transport blood to the liver.4
  5. Kidney problems: Cell destruction in PNH can lead to cell breakdown products like haemoglobin accumulation in the bloodstream. These can sometimes accumulate in the kidney tubules, leading to kidney problems.1,6
  6. Iron overload: Massive destruction of cells, especially red blood cells, can lead to iron release into the bloodstream, leading to iron overload. Excess iron in the bloodstream accumulates and can be highly dangerous for various organs, including the liver and heart.1,6


The diagnosis of PNH  begins with a medical history and clinical examination by your healthcare provider, who will inquire about your symptoms and medical history before carrying out tests to rule out other diseases. Some tests your healthcare provider may run are:1,6

Blood tests: Blood tests play a crucial role in diagnosing PNH.1,6 Several types of blood tests may be used to assess the presence of PNH-affected blood cells and the absence of specific protective proteins on their surface.1,6

  • Complete blood count (CBC): This measures the number of different types of blood cells. People with PNH often have low blood cell counts.1,6
  • Lactate dehydrogenase (LDH) level: LDH is an enzyme released from damaged or destroyed red blood cells, which would be higher if you had PNH.1,6
  • Bilirubin Level: Haemolysis (breakdown of red blood cells) releases bilirubin, a breakdown product of haemoglobin, into the bloodstream. Elevated bilirubin levels can be a sign of haemolysis occurring more than normal or faster.1,7

Flow cytometry: Flow cytometry assesses the presence of certain proteins on blood cell surfaces. It helps estimate the percentage of PNH-affected blood cells.1,6

Bone marrow biopsy: A bone marrow sample may be taken and examined under a microscope to assess the extent to which the mutated stem cells have replicated.1,6

Treatment and management

The main goals of treatment are to control the symptoms of haemolysis, improve quality of life, prevent life-threatening complications such as blood clots, and manage other associated issues.1,6 Treatment approaches vary based on the severity of the disease, the individual's symptoms, and their overall health status. Here's an overview of the treatment and management strategies for PNH:

  1. Monoclonal antibodies: Monoclonal antibodies are artificially produced proteins targeting a specific part of the immune system.1,7 Some  are used to block parts of the immune system that are responsible for cell destruction in PNH.1,7
  2. Supportive care involves treating a patient’s symptoms as they occur. For example, blood transfusions for people with anaemia, iron chelation therapy if iron overload occurs, and anticoagulation therapy for people at risk of blood clots or who have had blood clots.1,7
  3. Bone marrow transplantation: Severe cases of PNH may be treated with a bone marrow transplant. This involves replacing the patient's bone marrow with a healthy donor bone marrow, which can produce normal blood cells. This option is associated with significant risks and complications and is usually considered for specific patients and depends on many factors, including age, severity of disease, and the type of donor available.3
  4. Monitoring and follow-up: Regular monitoring of disease progression is essential to assess treatment effectiveness and manage any new symptoms that may arise.1,6


PNH is a complex disorder that can vary in severity from person to person.1,6 Its prognosis depends on the individual and what therapies they can access and respond to.1,6 However, the availability of targeted therapies that effectively manage the symptoms and complications of the disorder ensures that individuals with PNH can lead fulfilling lives.1,7 


How common is paroxysmal nocturnal haemoglobinuria? 

PNH is a rare disorder, with an estimated prevalence of 15.9  individuals per million in the general population and fewer than 1000 cases have been reported all over the UK. It affects people of all ages, races and genders.1,7

Can paroxysmal nocturnal haemoglobinuria be cured? 

Although bone marrow transplantation can be cured it, the procedure has many risks and complications. The success rate of the procedure is also highly individualistic and variable.1,6

Is paroxysmal nocturnal haemoglobinuria hereditary? 

No, Paroxysmal Nocturnal Haemoglobinuria is not hereditary. PNH results from a somatic mutation and is not typically inherited.1,6 It occurs spontaneously during a person's lifetime and can be aggravated by stress, surgeries or trauma.1,6


Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare haematological disorder caused by a spontaneous mutation in the PIGA gene during an individual's lifetime.1,8 It leads to the absence of protective proteins on the surface of blood cells. These unprotected cells are susceptible to attacks by  one’s own immune system, leading to symptoms like hemolysis, anaemia, thrombosis, and other complications.1,6

PNH's clinical presentation can vary widely; however, the most common symptom is dark red or brownish discolouration noticed during frequent bouts of urination late at night or during early mornings.1,6 Diagnostic commonly requires blood tests, flow cytometry, and clinical assessment.1,6 Therapies like monoclonal antibodies help reduce immune attacks on blood cells and play a big role in PNH management which is primarily focused on preventing future complications and managing the disease.1,6 In severe cases and to manage more serious complications, other therapies include blood transfusions, iron chelation therapy, supportive care, and bone marrow transplantation.1,6


  1. Shah N, Bhatt H. Paroxysmal nocturnal hemoglobinuria. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 24]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK562292/
  2. Murakami J, Shimizu Y. Hepatic manifestations in haematological disorders. Int J Hepatol. 2013;2013:484903.
  3. Sašo R, Marsh J, Čevreska L, Szer J, Gale RP, Rowlings P, et al. Bone marrow transplants for paroxysmal nocturnal haemoglobinuria. Br J Haematol [Internet]. 1999 Feb [cited 2023 Nov 24];104(2):392–6. Available from: https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.1999.01195.x
  4. Colden MA, Kumar S, Munkhbileg B, Babushok DV. Insights into the emergence of paroxysmal nocturnal hemoglobinuria. Front Immunol [Internet]. 2022 Jan 28 [cited 2023 Nov 24];12:830172. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8831232/
  5. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood [Internet]. 2014 Oct 30 [cited 2023 Nov 24];124(18):2804–11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215311/
  6. 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 [Internet]. 2014 May [cited 2023 Nov 24];99(5):922–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008114/
  7. Chapman J, Zhang Y. Histology, hematopoiesis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 24]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK534246/
  8. Miles B, Tadi P. Genetics, somatic mutation. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Nov 24]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK557896/
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Hadiza Bello

Doctor of Medicine - MD, All Saints University, Saint Vincent

Hadiza is a Medical Doctor who has worked in a clinical setting for five years, gaining valuable experience in diagnosing and treating a wide range of conditions.
She is currently pursuing an MSc in Infectious Diseases at the University of Kent
She is constantly exploring options to get involved in global health initiatives and is passionate about making healthcare more accessible and equitable for all.

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