Paroxysmal nocturnal hemoglobinuria: a plain-language guide

Paroxysmal nocturnal hemoglobinuria, usually shortened to PNH, is a rare blood condition that a person acquires during life rather than inherits, in which part of the immune system breaks apart red blood cells that have lost their normal protection [1,3].

This page provides general information. It does not replace advice from a doctor or another qualified healthcare professional.

Key facts

• PNH is acquired, not inherited. It begins with a genetic change in a single blood-forming cell in the bone marrow, and it is not passed on to children [1,3].
• The changed cells lose two surface proteins that normally protect them, so a part of the immune system called complement destroys them [1,3].
• It is rare. Published estimates of how many people are living with it range from about 1 to 38 per million, depending on what is counted [1,5,9].
• The main diagnostic test is a blood test called flow cytometry, which finds the unprotected cells directly [3,15].
• Blood clots were once the leading cause of death, and modern medicines have changed that picture substantially [10,11,12].
• Medicines control PNH rather than cure it. A stem cell transplant is the only current cure and is used only in selected situations [3,17].

On this page

• What is PNH?
• How common is it?
• What causes it?
• What are the symptoms?
• How is it diagnosed?
• How is it treated?
• Living with PNH
• Thinking about a clinical trial?
• Current research
• Support and further information
• Questions people often ask

What is PNH?

PNH is a rare blood condition in which some red blood cells are broken apart early by part of the person’s own immune system [1,3]. The breaking apart of red blood cells is called hemolysis.

It begins in the bone marrow, the soft tissue inside larger bones where blood cells are made [3,4]. One blood-forming stem cell there picks up a genetic change, then multiplies. The resulting family of cells is called a PNH clone [3,6].

Healthy blood cells carry protective proteins held in place by a small molecular hook called a GPI anchor. Two of them, CD55 and CD59, act as brakes on the complement system, a group of blood proteins that helps fight infection [1,9]. Cells in the PNH clone cannot build the anchor, so the brakes are missing and complement attacks them [1,3].

Everyone with PNH also has some degree of bone marrow trouble, meaning the marrow does not make enough healthy blood cells [3]. This is why PNH sits close to two other marrow conditions, aplastic anemia and myelodysplastic syndrome, and why a person can have PNH alongside either [3,7,15]. A large clone usually means clear hemolysis, and very small clones may cause none [9].

The name is misleading. Paroxysmal means coming and going, nocturnal means at night, and hemoglobinuria means hemoglobin in the urine, which can turn it dark [3,4]. Hemolysis in PNH is in fact continuous, and many people never notice dark urine [3,4,5]. An older name is Marchiafava-Micheli syndrome [1].

How common is it?

PNH is rare, and published figures differ because they count different things.

MedlinePlus Genetics gives 1 to 5 people per million [1]. A 2025 review reports 3.5 to 5.7 new cases per million each year and 13 to 38 people per million living with it [9]. England’s national PNH service describes about 5 people per million with hemolysis, plus roughly another 10 per million who have a small clone and few symptoms [5]. A United States charity estimates 400 to 500 diagnoses a year there [4]. A 2026 study of French hospital records found about 1 in 94,000 people recorded with PNH in 2022 [18]. Figures built from hospital records count only people diagnosed and coded, so they reflect access to specialist laboratories as much as true occurrence.

Men and women are affected in roughly equal numbers, and PNH occurs worldwide [3]. It can begin at any age, most often in the thirties or forties [1,3,9]. Aplastic anemia is more common in parts of East and Southeast Asia, and PNH may follow suit [3].

What causes it?

Genes are instructions inside our cells. PNH is caused by a change, often called a gene variant, in a gene named PIGA, which carries the instructions for building the GPI anchor [1,3].

Where and when that change happens is the part families care about. It is a somatic change, meaning it appears in one cell during a person’s life rather than being present from conception. It is not inherited, and a person with PNH does not pass it to their children [1,3]. Nothing a person did caused it.

One change alone is not enough. The altered stem cell also has to grow and outnumber healthy ones. Researchers think this usually happens when the immune system is mistakenly attacking the bone marrow, as it does in aplastic anemia, and the PNH cells survive that attack better than healthy cells do [3].

A very rare form involves a different gene, PIGT, and brings unusual inflammation as well, including meningitis not caused by infection, a rash and joint pain [1].

What are the symptoms?

Symptoms vary widely. Some people have almost none for years, and others have serious complications [3,14].

Common experiences include [1,3,9]:

• tiredness, weakness, breathlessness and a pounding heartbeat from anemia, meaning too few working red blood cells
• dark or cola-colored urine, often clearest first thing in the morning, though many people never see it
• yellowing of the eyes or skin, called jaundice
• difficulty or pain when swallowing, abdominal cramps, and in men erectile difficulties
• easy bruising, bleeding or repeated infections where the marrow makes too few platelets or white blood cells

Tiredness is the symptom people most often describe as having the largest effect on daily life [9]. Hemolysis tends to increase during infections, around periods, in pregnancy, and for some people after air travel [6].

Blood clots are the most serious complication, affecting up to about 4 in 10 people with untreated PNH, often in unusual places such as the veins of the liver, abdomen or brain [10].

When to seek urgent help. Get medical help straight away, or contact your PNH center, for sudden severe abdominal, back or chest pain, a swollen or painful leg, sudden breathlessness, a severe or unusual headache, weakness on one side or trouble speaking, or a fever while taking a complement medicine [3,6,19]. Dark urine lasting more than about two days also needs urgent advice [6].

How is it diagnosed?

Diagnosis is usually made by a hematologist, a doctor who specializes in blood [3]. PNH is often suspected when blood tests show hemolysis with no obvious cause, including a high level of an enzyme called LDH, a low level of a protein called haptoglobin, and a negative Coombs test, which rules out one common alternative [3].

The test that confirms it is flow cytometry on an ordinary blood sample. The machine reports which surface proteins each cell carries, so it can find cells missing their GPI-anchored proteins [3,15]. Guidelines advise looking at two separate proteins on at least two types of blood cell [9]. High-sensitivity versions pick up very small clones and are used to follow clone size over time [9,16]. A bone marrow sample is often taken too, showing whether aplastic anemia or myelodysplastic syndrome is also present [3,15].

Diagnosis is often delayed, since the early symptoms look like many other things and PNH is rare enough not to be the first thought. Once suspected, it is straightforward to confirm [15].

How is it treated?

Treatment aims to stop the destruction of red blood cells, prevent clots and support the bone marrow. Medicines control PNH rather than curing it [6,17].

Complement inhibitors. These block the complement system at one of several points.

• C5 inhibitors block the final step. Eculizumab, given into a vein every two or three weeks, was the first, and ravulizumab is a longer-acting version given less often [19,20,29,30]. Crovalimab can be injected under the skin monthly [24,28].
• Proximal inhibitors block an earlier step, which is why they exist. C5 inhibitors stop red cells bursting inside blood vessels, yet about half of people taking them stay anemic because coated red cells are cleared quietly by the liver and spleen instead. This is called extravascular hemolysis [9]. Pegcetacoplan is an infusion under the skin twice a week [21,25]. Iptacopan is a capsule taken twice daily, the first of this kind usable on its own [22,26,32]. Danicopan is a tablet taken three times a day, licensed only as an add-on for people still anemic on a C5 inhibitor [23,27,33].

Everyone taking these medicines needs vaccination against meningococcal bacteria, usually pneumococcus and Hib too, at least two weeks before the first dose [19,22]. Each carries the strongest warning United States regulators use, since blocking complement raises the risk of rare but rapidly serious bacterial infections [19,22,23].

Supportive care. Transfusions treat severe anemia, and folic acid and iron are given where needed [3]. Blood thinners treat clots and are used alongside a complement inhibitor once a clot has occurred [3,10].

The bone marrow, and cure. Complement medicines do not fix an underperforming marrow, so where marrow failure dominates, treatment follows that condition, often with medicines that damp down the immune system [3,9]. A stem cell transplant from a donor is the only current cure, and it carries real risks, so it is reserved for severe marrow failure or repeated dangerous clots [3,14,17].

Availability differs by country. England’s guidance recommends pegcetacoplan, iptacopan and danicopan in set circumstances [31,32,33], and Australia funds eculizumab and ravulizumab through the Pharmaceutical Benefits Scheme [34]. Licensed ages differ too: ravulizumab covers children from one month old in the United States and from 10 kg in the European Union [20,30].

Living with PNH

Care works best through a specialist center that sees PNH often. England runs a national service based in Leeds and London with outreach clinics [5].

Carry a card or wear a bracelet naming your diagnosis and your medicine, since emergency staff need to know quickly that you take a complement inhibitor, and keep standby antibiotics if your team provides them [19]. Tell any dentist, surgeon or other doctor about PNH before a procedure [6].

Fatigue is often underestimated. Pacing and gentle regular activity help, and it is worth asking whether anemia or low iron is contributing [9]. Note when hemolysis worsens, since infections, periods and travel are common triggers [6].

Pregnancy needs planning with both an obstetric team and a PNH team. In a study of 75 pregnancies in women taking eculizumab there were no maternal deaths, and about half needed a higher or more frequent dose as pregnancy went on. Most received a blood-thinning injection [13].

A rare, lifelong condition with an unfamiliar name is isolating, which is partly why the organizations below exist.

Thinking about a clinical trial?

Clinical trials are research studies that test whether a treatment works and is safe. PNH is an active research area. Deciding whether to look into a study is a personal choice, and it helps to take it in steps.

1. Understand what the study is asking

It is worth being clear on what a study involves:

• what the researchers are trying to learn
• what treatment is being studied, and what it is being compared with
• how long the study lasts
• what visits, tests or procedures are involved, and how often
• whether travel to a study site is required, and how far
• the possible benefits, and the known and unknown risks
• what happens when the study ends, including whether treatment continues

2. Consider possible medical suitability

Every trial has rules about who can take part. These are called eligibility criteria. Some describe who can join, and others who cannot. For a PNH study they might include a diagnosis confirmed by flow cytometry, a clone size above a set percentage, an LDH or hemoglobin level within set limits, a number of transfusions in the past year, whether a person has already taken a complement inhibitor and which one, an age range, up-to-date meningococcal vaccination, and whether aplastic anemia or another marrow condition is also present.

trialport’s medifit helps people consider information related to possible medical suitability. It does not diagnose a condition, confirm eligibility or replace formal screening by the study team.

Explore PNH clinical trials through trialport

3. Consider whether participation fits your life

Medical suitability is only part of the picture. A study can look right on paper and still be hard in practice. Worth thinking through:

• the time each visit takes, and how many there are
• travel, distance and who would come along
• work, school or caring responsibilities
• support from family and friends
• how you feel about infusions, injections or frequent blood tests
• whether a change of medicine would mean a change of routine, such as moving from a monthly infusion to daily tablets
• whether you understand the study well enough to decide

trialport’s readifit helps people reflect on their understanding, motivation, time, routines, support, emotions and practical arrangements.

4. Ask questions before deciding

Useful questions to put to a research team:

• Why is this study being carried out, and what is already known?
• What exactly would I need to do, and for how long?
• What are the known risks, and what is still unknown?
• Would I stop or change my current PNH medicine, and what happens to my hemolysis if I do?
• Could I receive a placebo? A placebo is a dummy treatment with no active medicine, used so researchers can compare results fairly.
• What happens if I have a bad episode of hemolysis or a clot during the study?
• What vaccinations or infection precautions would I need?
• Can I leave the study after joining, and what happens then?
• Are travel and other costs covered?
• Will I be told the results?

Taking part is voluntary. A person can ask questions, speak with people they trust and choose not to participate.

Search for clinical trials at app.trialport.com.

Current research

Research is concentrated in a few areas [9,17]:

• Fewer, easier doses. Work continues on medicines given monthly or less often, injections people can give themselves, and tablets taken at home rather than hospital infusions [9,17].
• Better control of extravascular hemolysis. Several investigational medicines aim at earlier steps of the complement system, so that anemia is controlled as well as bursting inside blood vessels. Published examples include zaltenibart, which blocks a protein called MASP-3, and early-stage medicines that block a protein called properdin. Neither is approved [9].
• Combining medicines. Pozelimab, an antibody against C5, is under study together with cemdisiran, which reduces how much C5 the body makes, as are pairings of a C5 inhibitor with a proximal inhibitor. Neither is approved for PNH [9].
• The bone marrow side of PNH. Current medicines do not repair a marrow that makes too few cells, and this remains an open problem [14,17].

Study status checked: 3 August 2026. Research moves and what is being studied changes, so this list will date. For current information, search at app.trialport.com.

Support and further information

In the United Kingdom, PNH Support is a charity run by people living with PNH and their families [6], and the National PNH Service publishes information from the specialist centers themselves [5]. The Aplastic Anaemia Trust covers the closely linked marrow conditions [7]. In the United States, the Aplastic Anemia and MDS International Foundation has the clearest step-by-step explanation of the biology anywhere [4], and the National Organization for Rare Disorders publishes a specialist-reviewed report [3]. In Canada, the Aplastic Anemia and Myelodysplasia Association of Canada runs peer support and local groups [8]. MedlinePlus Genetics and GARD are reliable government starting points [1,2]. Dedicated PNH organizations in Australia, New Zealand, Asia, Africa, the Middle East and South America could not be verified, and coverage there appears thin.

Questions people often ask

Is PNH inherited? Will my children get it?
No. The genetic change happens in one blood-forming cell during a person’s life, is not present in eggs or sperm, and is not passed on [1,3].

Is PNH a cancer?
No. It is a clonal condition, meaning cells descended from one changed cell, though not a malignant one. A small number of people later develop leukemia, which is why blood counts keep being monitored [1,3].

Why is it called nocturnal if my urine is never dark?
The name came from an early, mistaken idea that hemolysis happened only in episodes and mainly at night. It is in fact continuous, and many people never see dark urine. PNH can also disappear on its own, though rarely [3,5,6,11].

Is PNH still life-threatening?
It is serious and needs specialist care. Blood clots were once the leading cause of death, with median survival about 10 years after diagnosis before complement medicines existed. In one long-term study of people taking eculizumab, survival matched that of similar people without PNH [10,11,12].

Why do I need vaccinations before treatment?
Complement medicines switch off part of the defense against certain bacteria, especially meningococcus. Vaccination at least two weeks beforehand, plus an alert card and standby antibiotics, is standard [19,22].

Can I get pregnant with PNH?
Yes, with care from a PNH team and an obstetric team. Doses often need adjusting, and blood-thinning treatment is usually used [13].

Related trialport information

• Search for PNH clinical trials
• medifit and readifit explained
• How clinical trials work
• Questions to ask a clinical trial team
• Understanding informed consent
• Acute myeloid leukemia: a plain-language guide
• Understanding beta thalassemia: a plain-language guide
• More guides to blood and bleeding conditions

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Review information

Written by: trialport editorial team
Reviewed by: Keith Berelowitz, Founder and CEO, trialport
Reviewed on: 3 August 2026
Next review due: 3 August 2027
References last checked: 3 August 2026