Paroxysmal nocturnal hemoglobinuria (PNH) is considered a bone marrow failure disease. Some people with PNH may have only mild bone marrow dysfunction. Others may have severe bone marrow dysfunction that results in low levels of other types of blood cells. Continue reading to learn what you need to know about bone marrow failure in PNH.

1. Bone Marrow Failure Occurs When Your Bone Marrow Doesn’t Make Enough Blood Cells

Bone marrow is the soft tissue inside your bones. Its main job is to make new blood cells. There are three types of blood cells that your bone marrow makes:

• Red blood cells (RBCs) — Cells that help deliver oxygen from your lungs to the rest of your body
• Platelets — Cell fragments that help your blood clot
• White blood cells (WBCs) — Cells that help your body fight infections

By definition, everyone with PNH has some degree of bone marrow dysfunction.

Bone marrow failure occurs your bone marrow isn’t working properly to make one or more types of blood cells. This can result in lower-than-normal levels of certain blood cells (also called cytopenia). When there are low levels of all three types of blood cells, it’s called pancytopenia.

2. Everyone With PNH Has Some Degree of Bone Marrow Dysfunction

By definition, everyone with PNH has some degree of bone marrow dysfunction. Bone marrow dysfunction occurs when your bone marrow can’t make enough healthy blood cells. In people with PNH, the bone marrow can’t make enough healthy RBCs. Instead of making healthy RBCs, people with PNH make abnormal RBCs that are more likely to be destroyed by the immune system (called hemolysis).

Some people with PNH and a related condition,aplastic anemia, may have more severe bone marrow dysfunction.

Bone marrow failure can result from factors that develop during your life or factors passed down from your parents.

Aplastic anemia is a common cause of bone marrow failure. Aplastic anemia is a condition where the bone marrow can’t make enough blood cells for your body to function properly. Many people with PNH also have aplastic anemia. In fact, aplastic anemia is a major risk factor for developing PNH. People with aplastic anemia or a bone marrow failure disease have weaker bone marrow that can cause more abnormal RBCs to form in people with PNH.

3. PNH Can Cause Bone Marrow Failure and Vice Versa

PNH is one of the potential risk factors for bone marrow failure. Additionally, some types of bone marrow failure can cause PNH.

Bone marrow failure can be caused by acquired factors (factors that develop during your life) or inherited factors (factors passed down from your parents).

Acquired Bone Marrow Failure

Acquired bone marrow failure develops over time and is caused by something else, such as:

• Diseases — Including PNH, aplastic anemia, autoimmune disorders, and myelodysplastic syndrome (MDS)
• Cancer — Including multiple myeloma, leukemia, and lymphoma
• Medications — Such as chemotherapy or certain antibiotics
• Chemical exposure — Such as pesticides and insecticides
• Radiation
• Viral infections — Such as human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and cytomegalovirus

If PNH causes bone marrow failure, it’s called acquired bone marrow failure.

Inherited Bone Marrow Failure

Inherited bone marrow failure results from a mutation (change) passed down from your parents. People with this type of bone marrow failure have a mutation in the genes that regulate blood cell production.

Inherited bone marrow failure is often associated with other symptoms that appear together as part of a syndrome. Some common inherited bone marrow failure syndromes include Fanconi anemia, dyskeratosis congenita, and Shwachman-Diamond syndrome.

People with an inherited bone marrow failure disease may develop PNH.

4. Bone Marrow Failure Has Similar Symptoms as Severe PNH

Symptoms of bone marrow failure can vary depending on the cause. The most common symptoms of bone marrow failure are related to aplastic anemia. People with severe PNH may have similar symptoms.

To diagnose bone marrow failure, your provider will ask questions, perform a physical exam, and potentially order tests.

Symptoms of bone marrow failure may include:

• Anemia (low RBCs)
• Fatigue (extreme tiredness)
• Pallor (pale or grayish skin)
• Dyspnea (shortness of breath)
• Easy bruising and bleeding
• Petechiae (small spots caused by bleeding under the skin)
• Infections
• Fever

• Bone pain

5. Several Tests May Be Needed To Diagnose Bone Marrow Failure

A health care provider can diagnose bone marrow failure by asking about your symptoms, medical history (including a diagnosis of PNH), and family history.

Based on this information, your health care provider may order other tests, including:

• Complete blood count (CBC) — A test that measures the levels of your blood cells
• Bone marrow biopsy — A test in which a health care provider looks at a sample of your bone marrow under a microscope
• Imaging tests — Including ultrasound scans, magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) scans
• Blood tests to check for vitamin and mineral deficiencies — Including vitamin B12, folate, and copper
• Tests for other conditions — Including hepatitis (liver inflammation) or pregnancy
• Tests for infections — Such as HIV or EBV
• Genetic testing — Tests used to check for inherited bone marrow failure syndromes

If your health care provider suspects that a medication may be the cause of bone marrow failure, they may ask you to stop taking it.

Talk to your health care provider to learn which diagnostic tests are best for you.

6. Some PNH Drugs Don’t Affect Bone Marrow Failure

Drugs for the treatment of PNH that block RBC hemolysis (called complement inhibitors) don’t affect bone marrow failure. Examples of drugs that slow the breakdown of RBCs include:

• Eculizumab (Soliris)
• Pegcetacoplan (Empaveli)
• Ravulizumab (Ultomiris)

Complement inhibitors can reduce RBC hemolysis, decrease the risk of thrombosis (blood clots), and improve the quality of life for people with PNH. However, these treatments don’t affect how the bone marrow functions. Instead, these medications block the complement system — proteins in the immune system that are responsible for breaking down RBCs.

Because complement inhibitors don’t affect the bone marrow, other treatments may be recommended by your health care provider to treat bone marrow failure in PNH.

Other Treatments for Bone Marrow Failure

Treatment for bone marrow failure depends on several factors, including your symptoms, overall health, and the cause and severity of bone marrow failure.

Immunosuppressants are a common type of drug used to treat bone marrow failure. These medications help to stop the immune system from attacking the healthy cells in your bone marrow. Many people with aplastic anemia respond well to immunosuppressant treatments.

Some other treatment options for bone marrow failure include:

• Blood transfusion — A procedure where donated blood cells are given directly into a vein
• Growth factors — Medications that stimulate your bone marrow to make more blood cells
• Androgens — Hormones that help stimulate your bone marrow so it makes more RBCs

7. Bone Marrow Transplantation Is a Treatment Option for People With Bone Marrow Failure and PNH

Bone marrow transplantation (also called stem cell transplantation) is a treatment that may potentially cure PNH in addition to helping treat bone marrow failure. However, this treatment has significant risks and is usually recommended only for people with PNH who have severe complications, such as bone marrow failure.

During a bone marrow transplant, your bone marrow is replaced with healthy stem cells from a donor, which may be obtained from the donor’s blood or bone marrow. Doctors may recommend this procedure for people with PNH and bone marrow failure who are younger than 55 and who have a related donor match.

Your health care provider can help you understand if you’re a good candidate for a bone marrow transplant.

8. Bone Marrow Failure Increases Your Risk of Other Health Conditions

Even after treatment, bone marrow failure can increase your risk of certain health conditions, including:

• Blood cancers — Such as acute myeloid leukemia (AML)
• Solid tumor cancers — Such as osteosarcoma (bone cancer) and rhabdomyosarcoma (soft tissue cancer)
• Skin cancer — Such as squamous cell carcinoma (SCC)
• Infections
• MDS

Your prognosis (outlook) with bone marrow failure in PNH depends on several factors, including:

• The severity of your disease
• Your age
• Other health conditions
• How you respond to treatment

Talk to your health care provider for more information about your outlook based on your unique factors.

Talk With Others Who Understand

On myPNHteam, the social network for people with PNH and their loved ones, members come together to ask questions, give advice, and swap stories with others who understand life with PNH.

Are you living with bone marrow failure and PNH? How has bone marrow failure affected your quality of life? Share your experience in the comments below, or start a conversation by posting on your Activities page.