Understanding and managing fatigue caused by PNH

In the simplest terms, fatigue is extreme tiredness. A person experiencing fatigue will lack energy and motivation. They may also experience apathy (a lack of caring), depressive symptoms, boredom, irritability, anxiety, muscle aches, and feel physically tired. A person experiencing fatigue may feel a greater-than-normal desire for sleep, but sleep may not have a significant impact on their energy levels and motivation.

Fatigue can have many different causes, including physical and emotional burnout, poor nutrition, sedentary lifestyle, lack of sleep, medication side effects, and substance use. Fatigue can also be a symptom of a wide range of health conditions.

Fatigue is the most frequently reported symptom among people living with paroxysmal nocturnal hemoglobinuria (PNH), a rare disorder that causes the body to produce defective blood cells.

How PNH affects the blood

When a person has PNH, blood stem cells in the bone marrow produce blood cells that are vulnerable to attacks by a part of the immune system called the complement system. A person will experience episodes where the complement system destroys blood cells. This can lead to:

• Anemia, resulting from low levels of red blood cells and hemoglobin
• Increased risk of infections due to low levels of white blood cells
• Problems with bleeding, bruising, and clotting caused by low platelets

A common symptom of a PNH episode is hemoglobin in the urine (hemoglobinuria), which is typically most noticeable in the morning. Hemoglobin is a protein that is a main component of red blood cells (and gives red blood cells their red color). Urine that contains hemoglobin will be dark and reddish in color.

Symptoms vary from person to person, with some people experiencing mild symptoms and others experiencing severe symptoms. PNH can lead to life-threatening complications, including blood clots (thrombosis), chronic kidney disease, and bone marrow failure.

How PNH contributes to fatigue

Fatigue and other symptoms that occur with PNH are caused by the destruction of healthy blood cells. Even mild disease activity can cause significant fatigue.

Anemia

People with PNH often have anemia, and may experience fatigue as well as shortness of breath, headaches, and sometimes chest pain and rapid heartbeat. These symptoms will occur when the body does not have enough red blood cells to transport oxygen from the lungs to major organs and systems. Fatigue is also associated with low white blood cell counts and infections.

Low levels of nitric oxide

Nitric oxide is a gas that is naturally produced by the body and plays an essential role in the health and function of blood vessels. PNH can cause a person to have low levels of nitric oxide, which occur as the body uses up large amounts of nitric oxide in an attempt to clean up proteins from broken up blood cells. Low levels of nitric oxide reduce the flow of blood, oxygen, and nutrients through the body, which also contributes to fatigue.

Sleep disturbances

Sleep disturbances are also common among people with PNH and can also contribute to fatigue. Symptoms like pain, heart palpitations, and emotional stress can make it difficult for a person to get restorative sleep.

Chronic kidney disease

Chronic kidney disease (CKD) occurs when there is damage and loss of function to the kidneys, a pair of organs that act as filters to the blood. CKD is common among people with PNH, and fatigue is a common symptom of CKD.

Stress

Stress can also contribute to fatigue, and PNH is often a stressful condition to live with—it requires ongoing treatment, higher medical costs, and living with a higher-than-average amount of uncertainty. Living with a chronic condition like PNH requires a lot from a person.

How can a person with PNH manage fatigue

If you are experiencing fatigue, talk to your healthcare providers. Fatigue, other symptoms you are experiencing, and how these symptoms impact your life are important considerations when making treatment decisions.

Blood transfusions may be needed to increase red blood cell counts and treat anemia. Complement inhibitors are currently the main treatments for PNH. Complement inhibitors are drugs that reduce the activity of the complement system and prevent the destruction of blood cells. These drugs can reduce the need for blood transfusions and improve fatigue.

You can also talk to your healthcare team about strategies for improving energy levels. These can include:

• Strategies for managing energy, such as taking naps
• Current levels of physical activity and exercising recommendations
• Diet, nutrition, and if dietary supplements are recommended
• Sleep habits, including sleep schedule, sleep disturbances, and anything that interferes with sleep
• Counseling, support groups, and other strategies to support mental and emotional health

It’s important to remember that PNH is a different experience for different people. Good communication with your healthcare team about what you are experiencing and how PNH is impacting your life is essential to identifying what you need from treatment.