Imagine waking up feeling more tired than usual or noticing dark-colored urine without any obvious reason. For some people, these symptoms might point to paroxysmal nocturnal hemoglobinuria (PNH), a rare disease that involves red blood cells. PNH affects about 13 people per 1 million in the United States. Without treatment, PNH can lead to serious and life-threatening problems.

Here are eight key facts about PNH — including causes and current treatments — that you can discuss with your doctor. With the right care and regular monitoring, many people living with PNH can improve their quality of life.

1. PNH Is a Form of Hemolytic Anemia

PNH is a rare type of hemolytic anemia. This means abnormal erythrocytes (red blood cells) break apart faster than your body can replace them. This process, known as hemolysis, occurs when a part of the immune system — the complement system — mistakenly attacks red blood cells.

The complement system helps keep your body healthy by finding and destroying disease-causing invaders like viruses and bacteria. Normally, red blood cells are coated with proteins that protect them from the complement system. However, in PNH, genetic mutations (changes) cause red blood cells to lose these protective proteins, so the immune system destroys them.

PNH often occurs with conditions that cause bone marrow failure, including aplastic anemia and myelodysplastic syndromes.

PNH is also caused by problems with hematopoietic stem cells (HSCs), which are found in the bone marrow. These abnormal stem cells produce defective red blood cells, which can lead to anemia (low levels of red blood cells), an increased risk of thrombosis (blood clotting), and low levels of white blood cells and platelets. This weakens your body’s ability to fight infections and stop bleeding.

2. PNH Symptoms Affect Many Parts of Your Body

Symptoms of PNH can vary from person to person and may range from mild to severe. Common symptoms include:

• Hemoglobinuria (reddish or dark urine, especially in the morning)
• Severe fatigue
• Shortness of breath
• Lower back or abdominal pain
• Kidney problems
• Erectile dysfunction (trouble getting or keeping an erection)

Be sure to talk to your doctor if you think you have signs or symptoms of PNH.

3. Your Doctor May Assign You a PNH Type

Doctors group PNH in different types based on symptoms and laboratory test results. The three types of PNH are:

• Classic PNH — You have common symptoms like fatigue, dark urine, or blood clots.
• PNH with another bone marrow disorder — You have PNH along with a condition that affects the body’s ability to make blood cells.
• Subclinical PNH — A small number of abnormal PNH cells are found in your blood, but you don’t have symptoms or signs of red blood cell destruction.

Knowing your PNH type helps your doctor choose the best treatment plan for you.

4. PNH Is Linked to a Gene Mutation

Two factors lead to PNH. A gene mutation develops in hematopoietic stem cells, and these abnormal cells start growing out of control.

PNH is usually caused by a mutation in PIGA, a gene involved in making glycosylphosphatidylinositol (GPI) anchors, which attach protective proteins to the surface of blood cells. These anchor proteins act like a shield, signaling to the immune system that the cells belong there and shouldn’t be attacked. When the PIGA gene isn’t working, your complement system destroys the unprotected red blood cells.

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.

This gene mutation is acquired, meaning it happens during a person’s lifetime. It isn’t inherited from your parents and can’t be passed on to your children. Researchers are still not sure why this mutation occurs.

If only a few HSCs have a gene mutation, you may never develop symptoms. Many people have a small number of PNH cells without knowing it. However, PNH becomes a problem when the abnormal HSCs multiply too quickly and crowd out normal HSCs.

Scientists don’t fully understand why the mutated HSCs can grow so aggressively, but they believe additional gene mutations or immune system disorders — such as bone marrow failure from a condition such as aplastic anemia — may help these abnormal cells expand.

5. PNH May Be Linked to Other Serious Conditions

If you have PNH, you may be at risk of other conditions related to PNH. This blood disorder often occurs with conditions that cause bone marrow failure, including aplastic anemia and myelodysplastic syndromes.

PNH can also lead to serious complications, including:

• Pulmonary hypertension (high blood pressure in the arteries that carry blood from the heart to the lungs)
• Life-threatening thrombosis
• Acute myeloid leukemia
• Chronic kidney disease
• In rare cases, meningitis, inflammatory bowel disease, or other immune-related inflammation

Schedule regular follow-up visits with your healthcare team to make sure your treatments are working and to watch for any complications.

6. Your Doctor Will Order Blood Tests and Other Studies To Diagnose 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.

Blood tests that may reveal signs of PNH include:

• Complete blood count (CBC) — Measures levels of red blood cells, white blood cells, platelets, and hemoglobin (the oxygen-carrying protein in red blood cells)
• Reticulocyte count — Gives the count of immature red blood cells, which may rise if your body is trying to replace destroyed red blood cells
• Bilirubin test — Measures a pigment made when red blood cells break down
• Lactate dehydrogenase (LDH) test — Checks for an enzyme that’s often elevated when red blood cells are damaged

These diagnostic tests can point to certain PNH-related problems, but other health conditions may cause similar results. Doctors usually confirm a PNH diagnosis with flow cytometry. This test checks whether your blood cells are missing specific surface proteins that protect them from your immune system. A lack of these proteins is a key sign of PNH.

Your doctor may also order a bone marrow test to check for bone marrow failure and see if your body is making enough healthy blood cells. This test involves using a hollow needle to take a small sample of bone marrow, usually from your pelvic bone or breastbone. The sample cells will be examined for abnormalities.

7. PNH Treatments Are Available

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. Instead, your doctor may monitor your condition and begin treatment if your PNH worsens.

Some medications can help by blocking the complement system, preventing immune cells from attacking red blood cells. Complement inhibitors include:

• Crovalimab-akkz (PiaSky)
• Danicopan (Voydeya)
• Eculizumab (Soliris) and its biosimilars (Bkemv, Epysqli)
• Iptacopan (Fabhalta)
• Pegcetacoplan (Empaveli)
• Ravulizumab (Ultomiris)

If you have bone marrow failure due to aplastic anemia or another condition, your doctor may recommend immunosuppressive therapy to stop your immune system from attacking your HSCs.

Supportive care can also help ease symptoms and improve your quality of life. Supportive treatment of PNH may include:

• Iron or folate supplements to support red blood cell production
• Growth factor medications to stimulate blood cell growth
• Blood transfusions to replace lost or damaged blood cells
• Anticoagulants (blood thinners) to help prevent dangerous blood clots

The only potential cure for PNH is a bone marrow transplant. This procedure involves using chemotherapy to destroy abnormal HSCs, followed by an infusion of healthy HSCs from a donor. If the transplant is successful, your body can begin making normal blood cells again. However, this procedure carries serious risks, so it’s usually reserved for people with severe or life-threatening PNH.

Researchers continue to develop and test new treatments in clinical trials. If you’re interested in participating, ask your doctor about current and upcoming studies. In addition, always discuss potential side effects with your doctor before starting a new treatment option.

8. The PNH Prognosis Has Improved With New Therapies

The prognosis (outlook) for PNH has improved greatly in recent decades. In the past, the average life expectancy after diagnosis was 10 to 20 years. Today, with the use of complement inhibitors, many people with PNH can live a normal life span.

Your individual prognosis may depend on several factors, including your symptoms, lab results, and whether you have bone marrow failure or other complications. If you’re diagnosed with PNH, talk with a hematologist (a doctor who specializes in blood disorders) about what you can expect and how best to manage your health.

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On myPNHteam, people share their experiences with paroxysmal nocturnal hemoglobinuria, get advice, and find support from others who understand.

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