If you are living with paroxysmal nocturnal hemoglobinuria (PNH), you probably already know that it’s a rare disease. About 12 or 13 out of every 1 million people in the United States live with PNH. This statistic shows that PNH is not common, and being diagnosed with it means you are part of a small group.

PNH is a disease that happens when your immune system attacks your red blood cells, causing them to break apart. This process is known as hemolysis. The loss of red blood cells results in anemia when you no longer have enough red blood cells to carry oxygen to your tissues.

PNH can be grouped with autoimmune hemolytic anemia (AIHA). Like PNH, these are illnesses in which the body attacks and destroys red blood cells. The most common type of AIHA is warm AIHA. Cold AIHA includes cold agglutinin disease (CAD) and paroxysmal cold hemoglobinuria (PCH).

What Causes PNH?

The part of your immune system that targets your red blood cells is called the complement system. The complement system helps keep your body healthy by finding and destroying disease-causing invaders like viruses and bacteria. Normal red blood cells are coated with proteins that signal to your complement system that the cells are safe and shouldn’t be attacked. However, in PNH, genetic mutations result in red blood cells without these signaling proteins. The complement system assumes these red blood cells are dangerous invaders and destroys them.

PNH is also caused by problems with your hematopoietic stem cells (HSCs). These cells are found in your bone marrow and are responsible for making all of the different cells in your blood. Abnormal HSCs may lead to low levels of not only red blood cells but also white blood cells, which help fight infection, and platelets involved in blood clotting after injuries.

Gene Mutations

In PNH, HSCs develop a gene mutation, and then these defective cells start growing out of control.

A mutation is a change in the DNA sequence of a gene. PNH is typically caused by a mutation in the PIGA gene. This gene helps make the protein coating on your red blood cells. Due to the mutation on the PIGA gene, your red blood cells lack protection and are destroyed by your complement system. This gene mutation isn’t inherited from your parents. Instead, it develops throughout life. You won’t pass the PIGA mutation on to your children.

If just a few HSCs have a gene mutation, you may never experience symptoms. Many people have a small number of PNH cells and never find out. However, PNH develops when the abnormal HSCs expand too quickly and crowd out your normal HSCs.

Your HSCs may grow out of control if they develop additional gene changes besides the PIGA mutation. If your immune system is suppressed, that might also prevent it from getting rid of these damaged cells. This can happen if you develop bone marrow failure from other health conditions.

Signs and Symptoms of PNH

Some common PNH signs and symptoms include:

• Dark or reddish urine
• Headaches
• Muscle or joint pain
• Abdominal pain
• Anemia, leading to fatigue, shortness of breath, irregular heartbeat, pale skin, jaundice (yellow skin), or irritability
• Abnormal bruising or bleeding
• Frequent infections
• Swallowing problems
• Erectile dysfunction (trouble achieving or maintaining an erection)

Types of PNH

Your doctor may classify your PNH into a category based on your symptoms. In classic PNH, people develop some of the common symptoms listed above. Subclinical PNH occurs when a small number of abnormal PNH cells can be detected, but you don’t have symptoms. If your symptoms are severe, you may have PNH along with bone marrow failure syndrome, meaning that HSCs produce very few blood cells.

Diagnosing PNH

Some people first realize they have PNH after they develop symptoms. Others may discover a problem when routine blood tests come back with abnormal results.

The blood tests listed below can uncover signs of PNH. However, other health conditions may also lead to the same test results.

• Complete blood count (CBC) — If you have PNH, this test may show that you have low levels of red blood cells, white blood cells, platelets, or hemoglobin (a protein normally found in red cells).
• Reticulocyte count — Reticulocytes are immature red blood cells. Levels may rise during PNH as your body tries to replace the destroyed red blood cells.
• Haptoglobin test — You may have PNH if you have low levels of haptoglobin, a protein that helps get rid of any extra hemoglobin that spills into your bloodstream when red blood cells are destroyed.
• Bilirubin test — PNH is often characterized by high levels of bilirubin, a pigment made when red blood cells break down.
• Lactate dehydrogenase (LDH) test — LDH is an enzyme that serves as a sign of cell damage. Levels may rise if you’re experiencing hemolysis.

Doctors usually confirm PNH with a test called flow cytometry, which detects proteins attached to the outer membranes of blood cells. If you have PNH, flow cytometry will show that your cells do not have the proteins that offer protection from the complement system.

Your health care team may also recommend bone marrow tests to look for signs of bone marrow failure and determine whether your HSCs can produce enough healthy blood cells. During this test, your doctor will remove a small sample of cells by inserting a long needle into the bone marrow in your pelvic bone or breastbone. These cells will then be analyzed to look for abnormalities.

Treating PNH

Your doctor will recommend PNH treatments based on your symptoms and whether you have bone marrow failure. If you have very mild PNH, you may not need treatment right away. Your doctor may monitor your condition and begin treatment if your PNH worsens.

Certain medications can block your complement system, preventing immune cells from attacking your red blood cells. Complement inhibitors include:

• Eculizumab (Soliris)
• Ravulizumab (Ultomiris)
• Pegcetacoplan (Empaveli)
• Iptacopan, currently in clinical trials for treating PNH

If you experience bone marrow failure due to aplastic anemia or another condition, your doctor may recommend taking immunosuppressive therapy to prevent your immune system from killing your HSCs.

While living with PNH, you may also receive supportive care. These treatments can help eliminate symptoms and boost your quality of life. Supportive care includes:

• Dietary supplements including iron or folate because your body needs these nutrients to make more blood cells
• Growth factors such as erythropoietin, which encourage your HSCs to make more red blood cells
• Hormones called androgens that promote red blood cell production
• Blood transfusions, in which blood cells from a donor are given as an infusion into your veins
• Anticoagulants (blood thinners), medications that help prevent blood clots

The only treatment that can potentially cure PNH is bone marrow transplantation. During this procedure, you are given chemotherapy to kill your abnormal HSCs, and then you receive an infusion of healthy HSCs from a donor. A bone marrow transplant may enable your body to start producing normal blood cells again. However, this treatment is usually only recommended for those with life-threatening PNH, as it’s dangerous and doesn’t always work.

Researchers are continually creating new treatments and testing them through clinical trials. If you are interested in participating in the latest research, ask your doctor for information about current and upcoming studies.

Conditions Related to PNH

PNH often occurs with conditions that cause bone marrow failure, including aplastic anemia and myelodysplastic syndromes (MDS). These conditions are also caused by problems with the HSCs, leading to low levels of one or more blood cell types. Aplastic anemia and MDS may occur first and lead to an increased risk of PNH, or they may develop after you have a PNH diagnosis.

PNH can also lead to other conditions, including:

• Pulmonary hypertension (high blood pressure in the blood vessels that lead from your heart to your lungs)
• Blood clots
• Paroxysmal cold hemoglobinuria (a type of cold AIHA)
• Acute myeloid leukemia
• Meningitis, inflammatory bowel disease, or other types of inflammation-related problems
• Rarely, kidney damage or kidney disease

Your health care provider can help you manage other health concerns and understand your risk of developing other conditions.

Your Outlook With PNH

The prognosis (outlook) for PNH has improved greatly in recent decades. In the past, people with PNH lived for an average of 10 to 22 years after the condition developed. However, complement inhibitors now help people live longer. Some experts predict that people with PNH now live as long as those without the condition, although additional studies are needed.

The prognosis of PNH can vary depending on several factors such as other health conditions. Generally, with advancements in medical treatments and therapies, the outlook has improved in recent years. However, it is essential to note that PNH is a complex condition, and the prognosis can be different for everyone. Ask your doctor what to expect based on your health considerations.

Find Your Team

On myAIHAteam, the site for people with AIHA and their loved ones, members come together to ask questions, offer advice, and share their stories with others who understand life with AIHA.

Have you been diagnosed with AIHA or PNH? Share your experience in the comments below, or start a conversation on your Activities page.