Paroxysmal nocturnal hemoglobinuria (PNH)

Definition

Paroxysmal nocturnal hemoglobinuria is a rare disease in which red blood cells break down earlier than normal.

Alternative Names

PNH

Causes

People with this disease have blood cells that are missing a gene called PIG-A. This gene allows a substance called glycosyl-phosphatidylinositol (GPI) to help certain proteins stick to cells.

Without PIG-A, important proteins cannot connect to the cell surface and protect the cell from substances in the blood called complement. As a result, red blood cells break down too early. The red cells leak hemoglobin into the blood, which can pass into the urine. This can happen at any time, but is more likely to occur during the night or early morning.

The disease can affect people of any age. It may be associated with aplastic anemia, myelodysplastic syndrome, or acute myelogenous leukemia.

Risk factors, except for prior aplastic anemia, are not known.

Symptoms

Symptoms may include:

Abdominal pain
Back pain
Blood clots, may form in some people
Dark urine, comes and goes
Easy bruising or bleeding
Headache
Shortness of breath
Weakness, fatigue
Pallor
Chest pain
Difficulty swallowing

Exams and Tests

Red and white blood cell counts and platelet counts may be low.

Red or brown urine signals the breakdown of red blood cells and that hemoglobin is being released into the body's circulation and eventually into the urine.

Tests that may be done to diagnose this condition include:

Complete blood count (CBC)
Coombs test
Flow cytometry to measure certain proteins
Ham (acid hemolysin) test
Serum hemoglobin and haptoglobin
Sucrose hemolysis test
Urinalysis
Urine hemosiderin, urobilinogen, and hemoglobin
Lactate dehydrogenase (LDH) test
Reticulocyte count

Treatment

Steroids or other medicines that suppress the immune system may help slow the breakdown of red blood cells. Blood transfusions may be needed. Supplemental iron and folic acid are provided. Blood thinners may also be needed to prevent clots from forming.

Soliris (eculizumab) and Ultomiris (ravulizumab) are medicines used to treat PNH. They block the breakdown of red blood cells.

Bone marrow transplantation can cure this disease. It may also stop the risk for developing PNH in people with aplastic anemia.

All people with PNH should receive vaccinations against certain types of bacteria to prevent infection. Ask your health care provider which ones are right for you.

Outlook (Prognosis)

The outcome varies. Most people survive for more than 10 years after their diagnosis. Death can result from complications such as blood clot formation (thrombosis) or bleeding.

In rare cases, the abnormal cells may decrease over time.

Possible Complications

Complications may include:

When to Contact a Medical Professional

Contact your provider if you find blood in your urine, if symptoms worsen or do not improve with treatment, or if new symptoms develop.

Prevention

There is no known way to prevent this disorder.

References

Araten DJ, Brodsky RA. Paroxysmal nocturnal hemoglobinuria. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice. 8th ed. Philadelphia, PA: Elsevier; 2023:chap 32.

Michel M. Autoimmune and intravascular hemolytic anemias. In: Goldman L, Cooney KA, eds. Goldman-Cecil Medicine. 27th ed. Philadelphia, PA: Elsevier; 2024:chap 146.