Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease in which the immune system breaks apart the red blood cells (RBCs) in the body. The medical term for this premature rupture of RBCs is hemolysis.
RBCs carry hemoglobin to distribute to the cells in the body, and hemolysis releases the hemoglobin into the bloodstream. This release of hemoglobin leads to the symptoms of PNH.
The word paroxysmal means sudden and irregular, nocturnal refers to nighttime, and hemoglobinuria is the presence of hemoglobin in the urine, which causes it to darken. Scientists included the term nocturnal in the name of the disease because they noticed that many people — though not all — passed dark urine at night or early in the morning.
Most cases of PNH can be life threatening. The average survival period after diagnosis is 10 years, but some people live for several decades and only experience minor symptoms.
Keep reading to learn more about the causes and symptoms of PNH, as well as the diagnostic process and the treatment options.
PNH results from a genetic mutation in the stem cells that form RBCs and other immune cells. This mutation prevents a class of proteins called glycosylphosphatidylinositol (GPI)-anchored proteins from developing on the surface of RBCs.
In a healthy body, GPI-anchored proteins act as a shield around RBCs and protect them from destruction. In the case of PNH, since these proteins are missing, RBCs are vulnerable to the attack of other immune cells, which ultimately leads to their rupture.
According to the National Organization for Rare Disorders, the mutation responsible for PNH occurs for no apparent reason. The random nature of the mutation makes it difficult to predict which people are at risk of developing PNH in the general population.
Researchers have so far identified three subtypes of PNH:
- Classical PNH: People show evidence of the disease without another bone marrow-related disorder.
- PNH in the context of other primary bone marrow disorders: This subtype includes aplastic anemia and myelodysplastic syndrome.
- Subclinical PNH: People have some affected cells but no clinical or laboratory evidence of hemolysis or blood clots.
The severity of symptoms varies from one person to another. Some people have only mild symptoms, while others have severe symptoms and may need medication and regular blood transfusions.
People with PNH tend to receive a diagnosis months or years after their symptoms first appear. The reason for this is that the symptoms of PNH are nonspecific, so it is easy to mistake the condition for other diseases.
Some common symptoms include:
- unexplained tiredness, fatigue, or weakness
- cuts or wounds that bruise or bleed easily
- shortness of breath
- regular, and often severe, headaches
- signs of bleeding below the skin, such as spots of discoloration
- frequent infections
- flu-like symptoms
- back pain
- abdominal pain
- formation of blood clots, which affects 15–30% of people with PNH
- blood in the urine
It is important to remember that not everyone with PNH experiences all of these symptoms. Therefore, a person experiencing some of these symptoms should speak with a doctor about getting a diagnosis.
Doctors diagnose PNH by carrying out a thorough clinical and physical evaluation. They will also ask about the person’s medical and family history to rule out other conditions.
Another diagnostic test checks for an enzyme called
PNH treatment is often complicated and requires an experienced specialist and medical team. People with this condition should regularly update their healthcare team on their symptoms so that the team can adjust their treatment regimen accordingly.
In recent years, researchers have discovered newer treatments that improve the quality of life of people with PNH. These therapies have also increased the average life expectancy to more than 15–20 years from the time of initial diagnosis.
The Food and Drug Administration (FDA) approved the first drug to treat PNH in 2007. The drug, known as eculizumab (Soliris), is a humanized monoclonal antibody. It slows down or halts the breakdown of RBCs by blocking the immune system from destroying them, and it reduces the risk of blood clots. People with PNH need to take eculizumab every 2 weeks.
More recently, the FDA approved a medication called ravulizumab to treat PNH-linked hemolysis. Ravulizumab has a similar mechanism of action as eculizumab and provides comparable symptomatic relief. People with PNH need to take this drug every 8 weeks.
Depending on the severity of their symptoms, some people may require regular transfusions of RBCs, platelets, or both. This treatment ensures that they have adequate levels of blood cells to sustain normal bodily functions.
In milder cases of PNH, doctors prescribe folic acid and iron supplements to increase red blood cell production.
Doctors recommend bone marrow transplantation (BMT) for people who do not respond to eculizumab or have severe reductions in RBC, white blood cell, and platelet counts. To date, BMT is the only known cure for PNH. This procedure replaces the bone marrow stem cells with those from an external donor. In most cases, the donor is a family member, such as a sibling.
People with PNH should keep their doctor and medical team informed of their symptoms and any side effects that their prescribed treatments cause. PNH is now manageable with medication, although in severe cases, blood transfusions and bone marrow transplants may be necessary.
The doctor will determine the best course of treatment depending on the person’s age and medical history, as well as the extent of PNH.
Paroxysmal nocturnal hemoglobinuria is a rare blood disease that affects a person’s quality of life and increases the risk of health complications.
It is often difficult to detect, and many people go years before doctors can make a correct diagnosis.
Recent research has, however, shed light on the risks and impact of PNH and led to the discovery of new treatments that can help people manage these symptoms and risks in the long term.