Do people living with the rare disease paroxysmal nocturnal hemoglobinuria (PNH) experience more symptoms at night? After all, “nocturnal” is part of the name. Well, in this case, the name of the condition is a bit misleading.

If you have questions about PNH and symptoms you have at night, here’s what you need to know. Read on to learn how the disease got its name — and why the connection between PNH and the nighttime isn’t as straightforward as it sounds.

What Does the Name PNH Mean?

When you live with PNH, your red blood cells break apart in a process called hemolysis. Hemolysis is usually caused by a mutation in your PIGA gene that changes how your bone marrow makes red blood cells. As a result of this mutation, your red blood cells lack a protective layer that shields them from the immune system. Without this protection, proteins from your immune system, called the complement system, can attack and destroy them.

Each of the words in “paroxysmal nocturnal hemoglobinuria” describes part of how doctors originally understood this blood disease.

“Paroxysmal” means that something happens out of the blue or unpredictably. It may appear suddenly, then disappear just as fast. It may also show up at irregular intervals or only a few times in a person’s life.

“Nocturnal” means “at night,” and “hemoglobinuria” refers to the presence of hemoglobin in the urine. Hemoglobin gives red blood cells their color and carries oxygen. During the breakdown of red blood cells, hemoglobin is released into the bloodstream and filtered by the kidneys, which can make urine appear dark or cola-colored.

Put together, the name PNH describes a condition that was once thought to appear suddenly at night, causing dark urine due to hemoglobin released from destroyed red blood cells.

Is PNH More Active at Night?

The name of the condition is actually misleading. PNH isn’t truly nocturnal. The process in which red blood cells are destroyed and the kidneys process hemoglobin happens all the time, not just at night.

For years, people believed hemolysis in PNH happened at night. They would see darker urine in the morning and assume that the process happened while they slept. In reality, urine simply becomes more concentrated overnight, when you’re not drinking fluids or urinating as often. In some people, there’s only enough hemoglobin in the urine to change its color when it becomes more concentrated. During the day, the same process is happening — but because you’re more hydrated and urinating regularly, the color change isn’t as noticeable.

For years, doctors assumed hemolysis must happen at night, since darker urine appeared in the morning.

When researchers thought PNH only happened at night, they believed the cause was a process called acidosis. This condition happens when there’s too much acid in the body. This can happen if the lungs can’t exhale enough carbon dioxide or if the body produces more acid than the kidneys can eliminate.

Acidosis can sometimes get worse at night. Acidosis is connected to a number of changes in red blood cells and how thick the blood is. For a long time, researchers believed that acidosis activated the complement system, which then attacked red blood cells and broke them apart. This theory seemed to explain why people with PNH appeared to have more hemoglobin in their urine at night — but we now know that hemolysis happens all the time.

PNH Is Chronic, Even if You Don’t Always Notice Symptoms

It’s important to know that you can live with PNH and not experience dark urine. When you’re urinating regularly, the hemoglobin in your urine may not be concentrated enough to see. You may still have other symptoms of PNH, however. Your hematology provider can confirm a diagnosis with blood tests, such as a peripheral blood smear, even if you don’t see dark-colored urine.

It’s also worth noting that PNH isn’t truly paroxysmal either. PNH considered a chronic (long-term) condition, meaning the breakdown of red blood cells is always happening. However, it can get worse when the complement system becomes more activated. These activations are known as triggers.

PNH is a chronic disease, not a paroxysmal condition that only happens now and then.

Even if you rarely notice dark urine while living with PNH, you may still see it after you’ve experienced a trigger. If this happens, it’s important to let your hematologist know so they can help you manage your symptoms and adjust your care plan as needed.

What Triggers PNH?

Since your complement system is part of your immune system, it makes sense that you might notice more symptoms when your complement system is more active. When activated, your body might make more of those proteins — and those proteins may act more aggressively against your red blood cells.

You may notice more PNH symptoms when you’re experiencing potential triggers like stress, infection, or surgery.

Many situations can trigger your complement system, including:

• Stress
• Physical trauma
• Surgery
• Infections
• Certain medications
• Pregnancy

Since aplastic anemia and PNH are closely connected blood disorders and are risk factors for each other, you may end up living with both of these conditions. If you live with aplastic anemia in addition to PNH, traveling by airplane may cause medical issues. The elevation of an airplane cabin may make it harder for your body to get the oxygen it needs. If you have either condition and plan to fly, talk with your doctor first to make sure it’s safe for you.

Talk to a Healthcare Provider

If you’re treating your PNH but still notice symptoms, talk to your PNH specialist. They may be able to suggest changes to help better manage your condition. They might recommend you try new treatment options or make changes to avoid triggers. Staying in touch with your healthcare team can help you manage your condition more effectively, feel your best, and reduce the risk of serious complications.

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