Bone marrow failure
Paroxysmal nocturnal hemoglobinuria (PNH)
If you or someone you love has just heard this diagnosis, start here. This guide explains what the condition is, how it is usually treated and whether a transplant plays any part.
Paroxysmal nocturnal hemoglobinuria, or PNH, is an acquired blood disorder in which some blood cells lack protection from complement, part of the immune system. It can cause red-cell destruction and dangerous clots. Medicines usually lead treatment; donor transplantation has a selective role.
Other names and abbreviations
PNH, PIGA-mutant clonal complement-mediated hemolysis, AA/PNH overlap, Marchiafava-Micheli syndrome, Paroxysmal nocturnal haemoglobinuria
In short
- PNH is an acquired blood disorder in which some blood cells lack a protective coating. Without it, part of the immune system can destroy red cells.
- Medicines called complement inhibitors usually lead treatment and can reduce red cell destruction and clots. Vaccines and other steps help lower infection risk.
- A donor transplant is not the usual treatment. It may be considered for selected people with severe marrow failure, leukemia-type changes or complications medicine cannot control.
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Underlined words open a short explanation. See all terms
Where transplant fits
A donor transplantComing from another person. In an allogeneic, or donor, transplant, the stem cells come from a relative or an unrelated volunteer whose cells are a close enough match to the patient's. is generally not the usual treatment for classical PNH controlled with complement inhibitors. It can be appropriate for selected patients with severe marrowThe soft, spongy tissue in the center of most bones. Red bone marrow holds the blood-forming stem cells that make red blood cells, white blood cells and platelets. failure, myelodysplastic or leukemic disease, or exceptional uncontrolled complications.
Treatment depends on the exact diagnosis, disease stage, prior treatment and the person’s health.
Key facts
- Who it affects
- PNH is a rare acquired disorder. It can occur at any age but is most often diagnosed in young adulthood. A detectable PNH clone and symptomatic classical PNH are not the same finding.
- How common
- About 1 to 5 people per millionEstimated number of people affected, general population, region not stated; MedlinePlus Genetics, U.S. National Library of Medicine (updated February 2022) Source: How common
- Cells used in a transplant
- When transplantation is appropriate, the graft contains blood-forming stem cells from a suitable donor. Bone marrow, peripheral blood or cord blood may be selected according to the condition and transplant protocol.
- Where a donor fits
- Limited transplant role
The condition
What it is
PNH begins in a blood-forming stem cellYoung cells that can grow into every type of blood cell: red cells that carry oxygen, white cells that fight infection and platelets that help blood clot. They are found in the bone marrow and the bloodstream.. Its descendants lack certain protective surface proteins, leaving red cells vulnerable to complement-mediated destruction, called hemolysis.
The name refers to dark urine, but not everyone has this symptom and hemolysis is not confined to nighttime. PNH can occur with aplastic anemia or other marrow disorders, but these diagnoses are not identical.
Marked as affected: blood stem cells and red blood cells.
- Blood stem cell, Affected, In the bone marrow
- Myeloid line
- Red blood cells, Affected
- Platelets
- Granulocytes
- Monocytes
- Lymphoid line
- B cells
- Plasma cells, Develop from B cells
- T cells
- NK cells, Natural killer cells
- Myeloid line
What causes it
PNH usually involves an acquired change in PIGA, a gene required to attach protective proteins to blood-cell surfaces. The change occurs in a blood-forming cell rather than being present throughout the body and is generally not inherited by children.
A population of these altered cells is called a clone. Why a clinically important clone expands differs between people and can involve immune-mediated marrow injury. A small clone alone does not mean that someone has symptomatic classical PNH.
Symptoms and effects
Hemolysis can cause fatigue, breathlessness, jaundice, abdominal pain and dark urine. Blood clots may occur in usual or unusual locations and can be life-threatening.
Some people also have low blood counts because the marrow is not producing enough cells. Tests of hemolysis, blood counts, clone size, symptoms and clotting history help distinguish the problems that need treatment.
Diagnosis and treatment
How PNH is diagnosed
PNH is rare, so it can take a long time to find. Because the symptoms vary, many people first see other specialists, such as kidney, gut, heart or brain doctors. International experts suggest PNH testing for people with unexplained dark urine or unexplained red-cell breakdown (hemolysis). Testing is also suggested for unexplained blood clots in unusual places, such as veins in the liver, belly, brain or skin. People with aplastic anemia, some types of MDS, or lasting low blood counts with no clear cause are tested too.
The key test is flow cytometry on a blood sample. It checks red and white blood cells for certain surface proteins that PNH cells lack. A routine test can find PNH cells that make up 1% or more of cells. High-sensitivity tests can find as few as 1 in 10,000 cells (0.01%). The same test is used to follow the disease over time.
Finding a small PNH clone, for example during aplastic anemia care, is not the same as having classical PNH with red-cell breakdown.
How it is treated
Complement inhibitors reduce the immune attack on red cells and can reduce hemolysis and clotting complications. Several medicines act at different points in the complement pathway; eligibility, route of administration and access vary by country.
These medicines do not eliminate the PNH clone or directly correct severe marrow failure. Persistent anemia may have more than one cause and needs reassessment rather than an automatic assumption that the medicine has failed.
Complement blockade increases susceptibility to serious infections, including meningococcal infection. Vaccination, possible antibiotic protection and a plan for urgent symptoms are coordinated by the treating team. Vaccination does not remove all risk.
Allogeneic transplantation can replace the affected blood-forming cells but carries substantial risks. It is mainly considered for selected patients with severe marrow failure, myelodysplastic or leukemic disease, or exceptional circumstances involving uncontrolled PNH.
Kinds of treatment described for paroxysmal nocturnal hemoglobinuria (PNH): medicines and a donor stem cell transplant (for some people).
After diagnosis, the options described here
Medicines
Complement inhibitors reduce the immune attack on red cells and can reduce red cell breakdown and clots.
Donor stem cell transplant, For some people
Most people with PNH do not need a donor; a transplant is considered for some with severe marrow failure or MDS or leukemia.
These are the kinds of treatment this page describes, not a plan. Which ones fit, in what order and whether they are combined differs from person to person.
When transplant specialists are usually consulted
European transplant guidance (EBMT, 2025) generally does not recommend a donor transplant for classical PNH when complement inhibitors are available. It lists a transplant as a possible option when PNH comes with severe marrow failure (AA/PNH syndrome) or turns into MDS or AML. Because PNH shows up in so many ways, it advises input from a PNH specialist center.
Read the guidanceDaily life and the donor’s role
Living with the condition
Ongoing care may involve regular medicine, blood tests, assessment of breakthrough symptoms and monitoring for complications. Some medicines are infused; others are injected or taken orally. Treatment schedules differ.
Care teams usually explain which symptoms need urgent help and how treatment is handled during an infection, surgery or pregnancy. People with overlapping marrow failure may need transfusionsPutting blood, or parts of blood such as red cells or platelets, into a person's bloodstream through a vein. Some people with blood disorders need regular transfusions. or additional treatment alongside complement inhibition.
The donor’s role
A donor transplant is generally not the usual treatment for classical PNH that is controlled with complement inhibitors. An unrelated donor may matter when transplantation is appropriate for a particular person’s marrow failure or other serious complications.
Most people with PNH do not need a donor. When someone does need a transplant, it is usually because of another problem, such as severe marrow failure or a change to MDS or leukemia.
Looking ahead
Looking ahead
Outlook for PNH
The outlook for PNH has changed a great deal. In a London group followed before today's medicines, median survival was about 10 years after diagnosis. Blood clots and bleeding were the most common known causes of death. A few people in that group recovered on their own over time.
Complement inhibitors changed this picture. At the UK's Leeds PNH center, 79 people were treated with eculizumab from 2002 to 2010. Their survival was similar to that of people of the same age and sex without PNH. Clots became much less common on treatment. Today, care teams also watch for marrow failure and for changes toward MDSA group of cancers in which the bone marrow does not make enough healthy blood cells and abnormal cells appear in the blood or marrow. Also called myelodysplastic syndromes (MDS). Sometimes they turn into acute myeloid leukemia. or leukemia. Access to these medicines varies by country.
A donor transplant can replace the affected blood-forming cells, but it carries serious risks. In a European registry study, results were worse when the transplantA treatment that gives a patient healthy blood-forming stem cells through a vein. The cells travel to the bone marrow and replace faulty marrow or marrow damaged by treatment. They can come from the patient or a donor. was done because of blood clots. The authors concluded that a transplant is probably not a good choice for life-threatening clots in PNH.
About these numbers. Each one says which group of people it comes from, and the place and years where the source gives them. It describes what happened across that group, not what will happen to any one person. And a figure measured among people who had a transplant is not the same as the number of people who need one.
- About 10 years after diagnosisMedian survival before complement inhibitors
80 people with PNH referred to Hammersmith Hospital, London, 1940–1970, treated with supportive care (published 1995)
Read the source: Median survival before complement inhibitors - 68%Alive 5 years after a donor transplant
211 people transplanted for PNH at 83 EBMT centers, 1978–2007 (published 2012); 54% when the transplant was done because of blood clots
Read the source: Alive 5 years after a donor transplant
The transplant figure describes people who had a transplant, many before today's medicines. It does not describe everyone with PNH or predict any one person's outcome.
Common questions
Is PNH inherited?
In almost all cases, no. PNH is acquired, not inherited, and it is generally not passed on to children. It usually starts with a change in a gene called PIGA in one blood-forming stem cell. The blood cells that come from that stem cell lack surface proteins that normally protect them from complement, part of the immune system. A very rare inflammatory form involves an inherited gene change as well as an acquired one.
What are the symptoms of PNH?
The breakdown of red blood cells, called hemolysis, can cause tiredness, shortness of breath, yellowing of the skin or eyes (jaundice), belly pain and dark urine. Despite the name, not everyone has dark urine, and the breakdown does not happen only at night. PNH can also cause blood clots, sometimes in unusual places, which can be life-threatening. Some people also have low blood counts.
Does PNH need a bone marrow transplant?
Usually not. When classical PNH is controlled with medicines called complement inhibitors, a donor transplant is generally not the usual treatment. A transplant may be considered for selected people who also have severe bone marrow failure, MDS or leukemia, or rare PNH problems that medicines cannot control. It can replace the affected blood-forming cells, but it has serious risks.
Is PNH curable?
Medicines called complement inhibitors can reduce red-cell breakdown and clotting problems, but they do not remove the PNH cells, so ongoing care may involve regular medicine. A donor stem cell transplant can replace the blood-forming cells that make PNH cells, but it carries high risks. European transplant experts (EBMT, 2025) generally do not recommend a transplant for classical PNH, which mainly causes red-cell breakdown and clots, when complement inhibitors are available. A transplant is mainly considered when PNH comes with severe marrow failure or turns into MDS or leukemia, or when complement inhibitors are not available.
Is PNH the same as aplastic anemia?
No, but they can overlap. PNH is an acquired disorder in which some blood cells lack protection from part of the immune system. Aplastic anemia is a failure of the bone marrow to make enough blood cells. The two can occur together, and some people who have or were treated for aplastic anemia later develop PNH. A small PNH clone on its own does not mean someone has classical PNH.
Why the details matter
Complement-blocking medicines do not remove the PNH blood cells, and they do not directly treat severe aplastic anemia.
For your next appointment
Paroxysmal nocturnal hemoglobinuria (PNH)
From the Jada Bascom Foundation disease library, jadabascomfoundation.org. Printed .
Questions to bring to your care team
- How big is my PNH clone, and will you repeat the flow cytometry test? How often?
- Is my marrow also involved, such as aplastic anemia or MDS, and how does that change my care?
- If I still have anemia on treatment, is it from red-cell breakdown, low marrow output or something else?
- Which vaccines and emergency plan do I need for fever or infection while I take a complement inhibitor?
- What is the exact name of the diagnosis or subtype, and what does it mean for treatment?
- What is the goal of each treatment you are suggesting?
- What would make a transplant worth considering later on?
- Are there clinical trials that might fit?
- Where can our family find support during treatment?
A one-page list to take to the next appointment, with room for notes.
Supporting someone with a diagnosisSupport for patients and families
These independent organizations offer information and support. JBF is not affiliated with them.
- Aplastic Anemia and MDS International Foundation (AAMDSIF) Nonprofit that educates and supports patients and families living with PNH, aplastic anemia and related bone marrow failure diseases.Worldwide (US-based)
- Aplastic Anaemia Trust UK charity offering information and emotional support to people living with PNH or aplastic anemia, and to their families and friends.United Kingdom
Sources and further reading
- Paroxysmal nocturnal hemoglobinuria
MedlinePlus Genetics, US National Library of Medicine, Accessed 2026-09-05 - Acquired Bone Marrow Failure: Severe Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria
EBMT Handbook, 2024-04-11 - 2025 EBMT practice recommendations for transplantation and CAR-T
EBMT, 2025 - Signs and Symptoms
PNH National Service Leeds, Leeds Teaching Hospitals NHS Trust, Accessed 2026-09-24 - Paroxysmal Nocturnal Hemoglobinuria
National Organization for Rare Disorders (NORD), Accessed 2026-09-24 - Paroxysmal Nocturnal Hemoglobinuria (PNH)
Memorial Sloan Kettering Cancer Center, Accessed 2026-09-24 - Paroxysmal Nocturnal Hemoglobinuria - PNH
ARUP Consult, ARUP Laboratories / University of Utah, Accessed 2026-09-24 - Treatments
PNH National Service Leeds, Leeds Teaching Hospitals NHS Trust, Accessed 2026-09-24 - What is PNH?
PNH National Service Leeds, Leeds Teaching Hospitals NHS Trust, Accessed 2026-09-24 - Who should be tested? (International PNH Interest Group and International Clinical Cytometry Society indications)
PNH National Service Leeds, Leeds Teaching Hospitals NHS Trust, Accessed 2026-09-26 - Diagnosis (patient information)
PNH National Service Leeds, Leeds Teaching Hospitals NHS Trust, Accessed 2026-09-26 - Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry (abstract)
Cytometry Part B: Clinical Cytometry (Borowitz MJ, et al.), 2010; accessed 2026-09-26 - Natural history of paroxysmal nocturnal hemoglobinuria (abstract)
New England Journal of Medicine (Hillmen P, et al.), 1995; accessed 2026-09-26 - Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival (abstract)
Blood (Kelly RJ, et al.), 2011; accessed 2026-09-26 - Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria
Haematologica (Peffault de Latour R, et al.), 2012; accessed 2026-09-26
This information explains a condition and its treatments. It cannot diagnose an illness or recommend treatment for an individual. Your care team can explain how the evidence applies to you. Written and source-checked by the Jada Bascom Foundation. Each page lists the published sources it draws on.
Ways to help
Help another family understand.
Most people with paroxysmal nocturnal hemoglobinuria (PNH) are treated without a registry donor. A clear explanation can help the next family who hears this diagnosis, and many people with other blood cancers and blood disorders need a donor who is a stranger.
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More in the library
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