Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder that causes your red blood cells to break down before they should. This causes hemoglobinuria, or hemoglobin in your urine. Hemoglobin is a protein found in red blood cells.
With PNH, platelets are also more prone to clotting than usual. This can lead to potentially life threatening blood clots. People with PNH also have bone marrow dysfunction that can cause low blood cell levels.
Read on to learn more about PNH, including the cause, outlook, and treatment.
A mutation in the PIGA gene of a bone marrow stem cell causes most PNH cases. Bone marrow stem cells develop into blood cells. If the mutated stem cell expands and multiplies, PNH develops.
Mutated stem cells develop into blood cells that lack certain proteins that help protect blood cells from your complement system. This is a part of your immune system that breaks down bacteria, viruses, and other foreign organisms. The complement system mistakes PNH blood cells for foreign cells and destroys them.
People are not born with the PIGA mutation that causes PNH. Instead, they acquire it later in life. The mutation occurs randomly for no known reason.
Other conditions that affect your bone marrow may also allow the mutated stem cell to expand and multiply.
Red blood cells contain an iron-rich protein known as hemoglobin. If you have PNH and your complement system destroys red blood cells, your body gets rid of the hemoglobin through your urine.
This is known as hemoglobinuria. It can cause your urine to appear red, brown, or darker than usual.
Hemoglobinuria tends to be most noticeable in the morning because your urine becomes more concentrated during sleep. This explains the “nocturnal” in paroxysmal nocturnal hemoglobinuria. However, PNH is not active only at night.
To diagnose PNH, a healthcare professional will start by asking about your symptoms and medical history.
PNH symptoms vary from one person to another. Some people with PNH have episodes of red, brown, or dark-colored urine, especially in the morning. Other potential symptoms include:
- fatigue
- weakness
- dizziness
- headache
- back pain
- chest pain
- abdominal pain
- rapid heartbeat
- pale skin
- difficulty breathing, especially while exercising
- trouble swallowing
- esophageal spasms
- erectile dysfunction
A variety of conditions can cause these symptoms, not just PNH. So to learn what’s causing your symptoms, your physician may order one or more tests.
Flow cytometry is a blood test used to diagnose PNH. It can tell a doctor how many blood cells in your body carry the PIGA mutation.
Bone marrow transplantation is the only cure for PHN, but it carries a high risk of side effects. A doctor will recommend this procedure only if you have severe PNH that has not responded well to other treatments.
Other PNH treatments are available to reduce symptoms and lower your risk of complications.
If you have PNH, your recommended treatment will depend on how severe the condition is. Some people with PNH have stable, mild symptoms for many years. If the condition progresses, it can cause serious symptoms that may lead to life threatening complications.
Anticoagulants
If you have a clot, your doctor will likely prescribe an
Supplements
If you have few PNH symptoms, your doctor may recommend nutritional supplements like folic acid and
Biologic drugs
To treat more severe PNH, your doctor will prescribe eculizumab (Soliris, Alexion) or ravulizumab (Ultomiris).
These medications are monoclonal antibody complement inhibitors. They bind to complement component 5 (C5), which is an enzyme in the complement system that helps break down cells. When a medication binds to C5, it stops the enzyme from breaking down blood cells.
Eculizumab and ravulizumab-cwvz are given intravenously, meaning it’s administered via an IV line in a vein. If a doctor prescribes one of these medications, you will need to visit an infusion clinic to receive regularly scheduled doses.
Alternatively, a nurse may visit you at home to administer the medication.
Bone marrow transplant
People who do not respond to eculizumab, or who cannot obtain eculizumab in their country, may be candidates for a bone marrow transplant.
It’s important to note that complications can occur and can include:
- graft-versus-host disease
- infection
- organ damage due to microscopic blood clots in blood vessels
Eculizumab can reduce the incidence of graft-versus-host disease after a transplant.
Other treatments
A healthcare professional may also prescribe other treatments to manage PNH symptoms or complications.
People taking eculizumab need to get the
In the past, people with PNH had a reduced life expectancy due to limited treatment options. According to a 2020 research review, they typically lived for an average of 10 to 22 years after developing the condition.
But with improved treatments, survival rates have since improved. The average lifespan for people with PNH is now near the life expectancy of someone who does not have the condition. With treatment, people diagnosed with PNH can lead a long and fulfilling life.
In rare cases, PNH blood cells disappear and symptoms of the condition resolve on their own, according to
Bone marrow transplantation can also cause PNH to resolve. However, doctors prescribe this treatment only when PNH is very severe and other treatments have not worked well.
For most PNH cases, ongoing treatment is necessary to manage the condition.
Aplastic anemia is a known risk factor for PNH.
Aplastic anemia is a very rare blood disorder in which your bone marrow does not produce enough blood cells. In most cases, it’s an autoimmune condition that develops when your immune system attacks your bone marrow.
There are other types of anemia like iron deficiency anemia and sickle cell anemia. These are much more common types of anemia, and they do not raise your risk of PNH.
PNH can cause low levels of white blood cells, which play important roles in your immune system. As a result, PNH may weaken your immune system and raise your risk of infections and other conditions.
Higher risk of leukemia
PNH is also linked to an
Leukemia reduces the immune system’s ability to fight off infections.
Higher risk of bacterial infections
Certain PNH treatments may also affect your immune system.
These include eculizumab and ravulizumab, which raise your risk of meningococcal disease. This is a bacterial infection that can cause meningitis. If you take eculizumab or ravulizumab, your doctor will likely encourage you to get the meningitis vaccine, and they may prescribe preventive antibiotics.
Treatments that suppress the immune system
If you undergo bone marrow transplantation to treat PNH, your doctor will prescribe chemotherapy, radiation, or both to suppress your immune system. This will stop your immune system from destroying the donor bone marrow. It’s important to note that this procedure also raises your risk of infection.
Your doctor may prescribe immunosuppressive medication if PNH or aplastic anemia causes bone marrow failure. This type of medication raises your risk of infection.
Talk with your doctor to learn how you can lower your chances of developing infections while living with PNH.
PNH is a rare blood disorder that raises your risk of blood clots, infections, and leukemia.
If you have PNH, getting treatment can help reduce your symptoms, lower your risk of serious complications, and improve your long-term outlook.
To treat PNH, your doctor may prescribe nutritional supplements, medication, or a combination of both. If you have severe PNH that has not responded well to other treatments, they may recommend bone marrow transplantation.