What is paroxysmal nocturnal hemoglobinuria?

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disorder in which red blood cells break apart prematurely (called hemolysis). While the underlying defect is in the bone marrow, symptoms in individuals with PNH arise from circulating defective blood cells. The defective red blood cells are susceptible to premature destruction by a particular part of a person’s own immune defense called the complement.

What causes paroxysmal nocturnal hemoglobinuria?

Two factors are necessary for the development of PNH: a mutation of the PIGA gene in a blood-forming stem cell that it is not inherited, meaning it is not passed on to children, and occurs randomly for no apparent reason. Most likely, PNH arises when defective PNH stem cells survive the body’s own misguided immune system attack while healthy stem cells are destroyed.

What are the signs and symptoms of paroxysmal nocturnal hemoglobinuria?

The specific symptoms of PNH vary greatly from one person to another and affected individuals usually do not exhibit all of the symptoms associated with the disorder.

Possible symptoms include:

• Hemoglobinuria (dark-colored urine or blood in urine), most often noted in the morning upon awakening
• Anemia (low hemoglobin)
• Fatigue
• Rapid heartbeat
• Headaches
• Chest or abdominal pain
• Shortness of breath
• Difficulty breathing with exercise
• Blood clots

These symptoms of PNH are extremely rare in young children and more common in adolescents and adults.

How is paroxysmal nocturnal hemoglobinuria diagnosed?

Symptoms and some of the laboratory findings of PNH also occur in children with acquired aplastic anemia and myelodysplasia who have symptoms of hemolysis with no other known cause. A diagnosis is made based on a thorough clinical evaluation, a detailed patient history and laboratory testing. The main diagnostic test for individuals with suspected PNH or acquired aplastic anemia with hemolysis is a blood test that can identify populations of PNH cells, often referred to as PNH clones.

How is paroxysmal nocturnal hemoglobinuria treated?

At Children’s Hospital of Philadelphia (CHOP), patients with PNH are cared for by a multidisciplinary team of experts from the Division of Hematology. Therapies for PNH, or severe aplastic anemia with large PNH clones, is generally directed at the specific symptoms present. Over the past decade, a series of drugs have become available for the treatment of PNH that halt the breakdown of red blood cells and reduce the risk of thrombosis. The only curative treatment of PNH is bone marrow transplantation.