How to Manage PNH-Related Fatigue

PNH is an acquired blood disease. If you develop it, you’ll likely experience an increased rate of red blood cell destruction, blood clots, reduced bone marrow function, kidney issues, and hypertension.

An estimated 15.9 people out of 1 million are living with PNH. However, the actual number may be higher due to the number of people living with the condition with no diagnosis and underreporting.

PNH causes several non-specific symptoms, including fatigue and shortness of breath. In some cases, you may not experience any symptoms.

PNH occurs due to an acquired mutation on X-linked phosphatidylinositol glycan class A (PIG-A) gene. The mutation causes a decrease in the glycosylphosphatidylinositol (GPI) protein levels.

The GPI protein helps anchor other proteins to red blood cells, including proteins CD55 and CD59. When these proteins cannot attach to red blood cells, it leads to a perpetual state of destroying red blood cells known as hemolysis.

One of the most common symptoms associated with PNH is fatigue.

For many, it occurs due to PNH-related anemia. PNH destroys red blood cells faster than your body can replace them, leading to low red blood cell counts associated with anemia.

An estimated 11–27% of people who take eculizumab experienced breakthrough hemolysis. This is the return of hemolytic disease, where red blood cells are destroyed faster than they can be made. The cause is related to the cost of the medication and short half-life (effective time of medication).

Newer therapy options can help prevent breakthrough hemolysis. Ravulizumab is a newer medication option approved for use in 2018. Its half-life is 3 to 4 times longer than eculizumab, one of the more common treatment options. However, because it’s a newer medication, there are no long-term studies on its effectiveness or safety over many years of use.

PNH can also lead to kidney damage and chronic kidney disease (CKD). As CKD, the disease can cause several symptoms, including fatigue, chest pain, and changes in urinary output.

PNH and PNH-related fatigue can reduce your overall quality of life.

Recent studies suggest that the best way to improve fatigue and quality of life is through newer treatment approaches. Several newer medications that help improve fatigue include:

• pegcetacoplan
• crovalimab
• iptacopan
• danicopan

Each of the above showed fatigue improvement in studies looking at the drug’s effectiveness. Not all of the medications are available yet, and not all of these options will work well for everyone.

Medications like pegcetacoplan show significantly improved fatigue score compared to eculizumab. Pegcetacoplan helps to increase red blood cell counts and quality. It gained the Food and Drug Administration (FDA)’s approval in 2021.

The FDA accepted the application for approval for crovalimab, but it’s not yet available for use in the United States.

The FDA approved the use of ipatacopan for the treatment of PNH in December of 2023. This is the first oral monotherapy for PNH.

Danicon is currently under investigation for its safety and effectiveness. Clinical trials have so far shown positive results of the medication, indicating it’s generally well tolerated and effective for people who do not respond well to Eculizumab.

Each of the newer medications works slightly differently and may not be suitable for all people. If you’re interested in trying a new medication, you should consider talking with your healthcare professional about your options.

You also consider these additional steps to help manage fatigue.

Regular exercise

Regular exercise can help to moderately improve feelings of fatigue, vitality, and energy, according to a 2022 meta-analysis. The study did not specifically look at people living with PNH, but regular, consistent exercise should help decrease fatigue over time.

Energy-supporting diet

If you find that you have low energy, focusing on a balanced diet that includes fats, proteins, carbs, and fiber may help you gain some energy throughout the day. You may want to focus on fruits, vegetables, whole grains, and lean proteins.

Your healthcare professional may also recommend either eating more foods with iron and folate or taking supplements. These nutrients can help your body replace red blood cells destroyed due to PNH.

Regular sleep

You should aim to get between 7–9 hours each night. This is general advice and not specific to people living with PNH.

If you find that you have trouble getting enough sleep at night, you can try to make your room more accommodating to rest, also known as sleep hygiene. Tips to improve sleep hygiene include:

• using the bedroom for sex and sleeping only
• removing electronic devices
• using shades or blackout curtains to reduce light pollution
• avoiding large meals before bedtime
• avoiding caffeine in the late afternoon or evening

Drink more water

Dehydration can cause fatigue. If you find you’re extra tired, you may want to check your fluid intake each day. Drinking more water throughout the day can help you stay hydrated and avoid losing too much liquid, which can help give you more energy.

Fatigue is a common symptom of PNH. The disorder leads to anemia, which causes symptoms such as fatigue.

You may also experience breakthrough fatigue if the medication starts to wear off or becomes less effective.

Effective PNH treatment can help improve your symptoms, including fatigue. You may also find lifestyle changes, such as extra sleep, a balanced diet, and regular exercise may also help.

If you find your symptoms do not improve with treatment, you should consider speaking with a doctor about additional treatment options and to determine whether other medications or therapy may be appropriate for you.