PNH overview
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Paroxysmal nocturnal hemoglobinuria, or PNH, is a rare acquired disease characterized by the destruction of blood cells.
Hemoglobinuria refers to the appearance of the reddish protein hemoglobin in the urine, which is a common occurrence in PNH. The term paroxysmal means that PNH symptoms, which include fatigue, shortness of breath, and abdominal pain, tend to occur in sudden attacks.
The term nocturnal in the name PNH can be misleading, given that the destruction of blood cells that causes disease symptoms can happen continually throughout the day. However, the reddish discoloration associated with hemoglobinuria is often seen most clearly in the morning when urine is more concentrated.
What are the causes of PNH?
PNH is caused by a mutation in hematopoietic stem cells (HSCs) — cells found in the bone marrow that can give rise to all types of blood cells, including oxygen-carrying red blood cells, white blood cells that fight off infections, and platelets, which are small cell fragments involved in blood clotting.
Although PNH is caused by genetic mutations, the disease is not hereditary. Instead, PNH is an acquired disorder, meaning that the mutation that causes it appears over the course of a person’s life, due to errors that occur in cell division, rather than being inherited.
In most cases, PNH is specifically caused by mutations in a gene called PIGA, which is needed for the production of a molecule that attaches certain proteins to the surface of blood cells. These proteins normally act like a molecular identification badge that tells the immune system that blood cells are a healthy part of the body. Without these proteins, however, the immune system can mistake healthy blood cells for an infectious threat and launch an attack against them.
In PNH, it is the activation of the complement system, a part of the immune system, that leads to the destruction of blood cells, ultimately giving rise to its symptoms.
What are the symptoms of PNH?
Hemoglobinuria, the symptom that gives PNH its name, is characterized by discolored urine that looks dark reddish or brown.
Other symptoms of PNH may include:
- fatigue and weakness
- shortness of breath
- pale or yellowish skin
- headaches
- dizziness or lightheadedness
- abnormal heart rates
- trouble swallowing (dysphagia)
- throat muscles spasms
- abdominal pain
- erectile dysfunction
- abnormally heavy bleeding during menstruation (menorrhagia)
- dangerous blood clots (thrombosis)
- kidney damage.
Many of the symptoms of PNH mirror those of other conditions, which can make it difficult for patients to get a correct diagnosis.
How is PNH diagnosed?
The gold standard method for diagnosing PNH is examining blood cells to see if they lack the surface proteins that are characteristically absent in people with the disease.
This is done with a type of laboratory test called flow cytometry, which uses fluorescent antibodies that specifically bind to those surface proteins to stain cells. Blood cells then pass through a specialized machine that analyzes them one by one.
Other tests may be involved in the diagnostic workup of PNH.
- A lactate dehydrogenase assessment, known as an LDH test, measures the levels of a protein that is released when blood cells are destroyed. This test may be used to assess the severity of PNH.
- Bone marrow tests work to analyze HSCs. These tests usually are not needed to diagnose PNH itself, but are useful for identifying other conditions affecting the bone marrow, such as myelodysplastic syndromes (MDS) and aplastic anemia, which commonly co-occur with PNH.
Because PNH is rare and not all patients will experience its most telltale sign of urine discoloration, the disease can be misdiagnosed. It’s important to correctly diagnose PNH and start patients on treatment as early as possible so as to lower the risk of life-threatening disease complications.
What treatment is available for PNH?
Treatments available for PNH mainly aim to reduce the destruction of blood cells, typically through medication or a stem cell transplant. Supportive therapies also are available to help manage specific disease symptoms.
Medication
Nowadays, PNH is primarily treated with medications that block the activation of the complement system, and therefore can prevent complement-mediated blood cell destruction. Such medications have been found to ease disease symptoms and substantially reduce the risks of life-threatening complications.
There are six complement-blocking medications approved to treat PNH in the U.S.:
- Soliris (eculizumab)
- Ultomiris (ravulizumab-cwvz)
- PiaSky (crovalimab-akkz)
- Empaveli (pegcetacoplan)
- Fabhalta (iptacopan)
- Voydeya (danicopan).
Hematopoietic stem cell transplantation (HSCT)
Known as HSCT, hematopoietic stem cell transplantation is a procedure that involves collecting healthy HSCs from a donor and then administering powerful cell-killing treatments, such as chemotherapy, to destroy the faulty HSCs in a patient’s bone marrow. Healthy HSCs are then transplanted into the patient to repopulate the bone marrow and give rise to new healthy blood cells.
Because it can address the root cause of the disorder, HSCT is considered the only treatment for PNH that can be truly curative. However, HSCT is a highly invasive procedure that carries notable safety risks. Therefore, it’s usually not adopted as a first-line treatment for PNH in regions where complement-blocking treatments are available.
Supportive therapies
In addition to treatments that directly address the underlying cause of PNH, medical care for a person with the rare disorder commonly involves supportive therapies that can help reduce the risk of complications and manage specific symptoms. These may include:
- anticoagulation treatments to prevent dangerous blood clotting
- blood transfusions to help ease symptoms, such as fatigue, that are associated with low blood cell counts
- supplements of folic acid, an artificial form of a vitamin that HSCs need to make new blood cells
- therapies to control iron levels in the blood, which in PNH may be too low due to the destruction of blood cells, or too high due to regular blood transfusions
- continuous renal replacement therapy (CRRT), a form of continual dialysis that’s commonly used in PNH patients with kidney damage.
If the condition is left untreated, patients may face life-threatening complications such as chronic kidney disease, blood clots (thrombosis), or hemolytic anemia, in which red blood cells are destroyed faster than they can be made.
What is the life expectancy for people with PNH?
Prior to the development of complement-blocking therapies, the life expectancy for someone with PNH was about 10-22 years after the onset of symptoms. However, with modern treatments, the life expectancy for PNH patients is generally similar to that of the overall population.
Risk areas for people with PNH
There are certain precautions that people with PNH are recommended to take to minimize the risks of potential health complications in specific situations.
Air travel and high altitudes
At higher altitudes, there is less oxygen in the air. Thus, flying or travel to high altitudes can cause a worsening of symptoms for people who have anemia, or low levels of oxygen-carrying red blood cells. It’s recommended people with PNH talk to their doctor and get treatment to help manage anemia prior to flying or going anywhere that’s at an elevation higher than that to which they’re accustomed.
Pregnancy
PNH can increase the risk of pregnancy complications that affect both the mother and the child. These include preeclampsia, or high blood pressure sometimes accompanied by organ damage in the mother, preterm birth, and miscarriage. Pregnancy also may increase the risk of PNH-associated complications like blood clots and bleeding. Data suggest that complement-blocking treatment can reduce the risk of these complications, but there is still a notable chance that they may occur during pregnancy even with modern treatment.
It’s recommended that PNH patients who become pregnant consult with their healthcare team and find an obstetrician who specializes in high-risk births.
Vaccination
Attacks of PNH symptoms can be triggered by events that stress the body or activate the immune system.
Vaccines work by activating the immune system against a potential threat, and there have been reports of people with PNH who experience symptom attacks after receiving vaccines, such as those for the flu or COVID-19.
These are isolated case reports, however; there is not much solid data on the overall risk of attacks associated with vaccines in people with PNH. It’s recommended that people with PNH talk to their healthcare team about their specific situation to decide whether or not being vaccinated is the best option for them.
Surgery
Surgery may increase the risk of some PNH complications, particularly blood clots and excessive bleeding. It’s recommended PNH patients preparing to undergo surgery make sure their surgeon is aware of their condition and how to manage it. Taking blood thinners (anticoagulation treatments) soon after surgery also is often recommended.
PNH News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
FAQs about PNH
Ongoing blood cell damage associated with paroxysmal nocturnal hemoglobinuria (PNH) can put continuous stress on body systems and cause the disease to worsen over time for some patients. However, with modern therapies, it’s becoming increasingly common for patients to have stable disease for many years. PNH symptoms can vary significantly over time, and they often occur in sudden attacks, which may be triggered by certain events like physical exertion or infections.
Paroxysmal nocturnal hemoglobinuria (PNH) is estimated to affect 0.5 to 1.5 of every million people in the general population. In the U.S., about 500 people are diagnosed with PNH every year.
Prior to the advent of modern therapies, people with paroxysmal nocturnal hemoglobinuria (PNH) typically only lived a decade or two following the onset of the disease. However, with modern treatments, the life expectancy for someone with PNH is comparable to that of the general population.
Paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia are both bone marrow failure disorders that affect the stem cells that give rise to new blood cells. While PNH often co-occurs with aplastic anemia, the two conditions are distinct: PNH is caused by mutations in stem cells in the bone marrow, while aplastic anemia is driven by an autoimmune attack that damages bone marrow stem cells.
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