What Is Paroxysmal Nocturnal Hemoglobinuria?

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, potentially life-threatening disorder. It causes the red blood cells to break apart, a process called hemolysis. This releases hemoglobin from the red blood cells into the urine, which turns dark or blood-colored.

At first, the disease was thought to occur in bursts called paroxysms, and only at night. It was later discovered that the hemolysis is a constant process and it happens in the day as well.

People with PNH are at risk for thrombosis, or blood clots that develop in the veins. They also are at risk for bone marrow problems that lead to low production of all types of blood cells, which is known as deficient hematopoiesis.

Not everyone with PNH will see these effects to the same degree, or have the same symptoms—of which there are many. Blood tests are the main way that PNH is diagnosed. It can be managed with medications and blood transfusions, but the only potential cure for PNH is a bone marrow transplant.

This article offers an overview of PNH, including symptoms and possible causes. It also explains how PNH is diagnosed and treated, as well as complications that arise for people with PNH.

Types of PNH

PNH affects people of all sexes and ethnic backgrounds. It can occur at any age, but most people are diagnosed while they are in their 30s.

PNH has three main types. They are:

• Classical PNH, in which the disease is present but there is no other bone marrow disorder
• PNH with a primary bone marrow disorder, such as aplastic anemia or myelodysplastic syndrome, which can develop into acute myeloid leukemia (AML)
• Subclinical PNH, in which there are no symptoms but bloodwork done for another reason may reveal evidence of the disease

Symptoms

Symptoms of PNH correspond to the three main concerns of the disease discussed earlier: hemolysis, thrombosis, and deficient hematopoiesis. They each cause a different pattern of symptoms.

Hemolysis

• Hemoglobinuria, the dark or bloody urine that can happen throughout the day
• Anemia, a low red blood cell count
• Fatigue
• Headaches
• Irregular heartbeat
• Muscle spasms
• Erectile dysfunction

Thrombosis

Symptoms of thrombosis depend on where the blood clot occurs. If the clot is located in a vein of the liver, for example, jaundice and/or an enlarged liver may occur. A clot in the abdomen would cause pain in that area, while a blood clot in the head may bring on a headache or dizziness. Clots in the skin cause raised, painful, red lumps over large areas, such as the back.

Deficient Hematopoiesis

• Increased susceptibility to infections
• Fatigue
• Abnormal bleeding
• Mouth sores
• Dizziness
• Pale skin
• Rapid heartbeat
• Difficulty breathing

Causes

PNH is not an inherited disease, but it is caused by a change, or mutation, in the PIGA gene. The PIGA gene codes for an enzyme needed to make a chemical that helps anchor proteins to the cell membrane.

The change occurs randomly in a single stem cell, which then multiplies and expands, causing the disease. The reason PNH cells expand and multiply is not fully known. One likely cause is an autoimmune response that leads to bone marrow failure.

PNH will occur in most people diagnosed with acquired aplastic anemia. This is a serious disease in which bone marrow fails to make enough red blood cells, white blood cells, and platelets.

Diagnosis

Diagnosing PNH can be hard because it is a rare disease with symptoms that overlap with other bone marrow disorders. For this reason, the process will involve several types of tests.

Blood Tests

• Complete blood count (CBC): This shows how many of each blood cell type are in a blood sample.
• LDH test: High levels of an enzyme called lactate dehydrogenase (LDH) may point to hemolysis.
• Bilirubin test: High levels also indicate the destruction of red blood cells.
• Reticulocyte count: This measures the number of young red blood cells in the blood.
• Erythropoietin (EPO) test: EPO is a protein produced in the kidneys that stimulates the production of red blood cells.
• Vitamin B12 and folate level test: These are done rule out other causes of low red cell counts.

Flow Cytometry

A flow cytometry test is considered the gold standard for diagnosing PNH. This blood test can separate and analyze various components of blood. It reveals whether two key proteins, CD55 and CD59, are missing from the surface of blood cells.

Bone Marrow Test

In a bone marrow test, a hollow needle is used to remove liquid bone marrow from the pelvic bone. The sample is examined under a microscope to look at how well the marrow is producing blood cells.

Treatment

Treatments for PNH cannot cure the disorder. They manage the disease and/or treat specific symptoms. These treatments include:

• Oral medications: Two drugs have been the mainstay of treatment for managing PNH. They are Ultomiris (avulizumab-cwvz), which works by inhibiting the key C5 proteins involved in the disease, and Soliris (eculizumab), which works by halting the breakdown of red blood cells. In May 2021, the FDA also approved Empaveli (pegcetacoplan) as a new first-line treatment for PNH.
• Immunosuppressants: These drugs are used to stop the immune system from attacking the bone marrow. Some examples are antithymocyte globulin (ATG) and cyclosporine.
• Blood transfusions: Whole blood or specific components of blood from a donor are infused into your bloodstream to restore low blood counts.
• Growth factors: These are naturally-occurring hormones. They spur the bone marrow to make more of certain types of blood cells.
• Folic acid: Also called folate or vitamin B-12, folic acid helps bone marrow produce blood cells. It's easy to get enough folate in the diet but for people with PNH, supplements may help.
• Blood thinners: Blood thinners such as Coumadin (warfarin) may be used to reduce the development of blood clots.

Prognosis

The course and severity of PNH varies. People with a mild case are likely to have a normal lifespan. Those with PNH alongside aplastic anemia or MDS may have a shorter lifespan.

Blood clots are the main cause of severe complications and death in people with PNH.

Precautions

Living with PNH requires taking certain precautions. Some things to consider include:

Air Travel and High Altitudes

The farther you get from sea level—on a mountain, for example, or while flying in an airplane—the less oxygen there is. If you have anemia, this shortage can cause chest pain and fatigue.

Before you travel by air or go to a high-altitude spot, talk to your healthcare provider. They may want to check your red cell count and adjust treatments to prevent a reaction. It's important to drink plenty of water while flying, and to move your legs or walk around the cabin to prevent blood clots.

Vaccinations

There have been reports of PNH patients having bad reactions to flu shots, so it's important to talk to your healthcare provider about the risks and benefits of the vaccine. Your healthcare provider also may discuss any other vaccinations that you should have, and any PNH-related concerns.

Pregnancy

Having PNH can put both the mother and baby at risk. Risks to the mother include blood clots, preeclampsia, and a need for blood transfusions. Blood-thinning drugs like Coumadin reduce the risk of clots, but these drugs are not safe to use during the first trimester.

Risks to the baby include prematurity, low birth weight, stillbirth, and delayed growth and development. If you are considering pregnancy, find an obstetrician who specializes in high-risk births.

Surgery

Surgery can increase your risk of blood clots and cause serious bleeding if you have PNH. Your healthcare provider may want you to have a platelet transfusion prior to surgery, and then a blood thinner to take after the procedure.

Summary

Although PNH is rare, it is a serious chronic disease. It puts people at risk of blood clots, severe anemia, and bone marrow disorders—including leukemia—that can be life-threatening. Symptoms may differ, and there are many steps in diagnosing and treating PNH, but a bone marrow transplant remains the only potential cure.

A Word From Verywell

A diagnosis of PNH can be frightening, but there are more treatments than ever before. They are increasing life expectancy, and research on the disease continues. If you are interested, the National Organization for Rare Diseases can provide information on participating in a clinical trial.

Coping with PNH may take an emotional toll as well as a physical one. Resources like those from the AAMDS Foundation can help you find specialists, support groups, financial help, and more.