Overview of Paroxysmal Nocturnal Hemoglobinuria

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Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired, potentially life-threatening blood stem cell disorder. It was originally named for its symptom of dark-colored urine (hemoglobinuria) produced in the morning. It was thought that the abnormal breakdown of red blood cells (hemolysis) that caused the dark urine occurred in bursts (paroxysms) that occurred at night. Research has shown, however, that the hemolysis in PNH, caused by a biochemical defect, occurs throughout the day and does not occur in bursts. The change in urine color may occur at any time but is most dramatic in concentrated nighttime urine.

Improved understanding of paroxysmal nocturnal hemoglobinuria has redefined the disorder as having hemolysis, blood clots in veins (thrombosis), and a deficiency in the production of all types of blood cells (hematopoiesis). PNH affects both males and females of all ethnic backgrounds and may occur at any age, but is most commonly found among young adults.

Symptoms

Many people with PNH do not have symptoms. Symptoms of PNH depend upon whether hemolysis, thrombosis, or deficient hematopoiesis is present. Here are symptoms that accompany each one:

  • Hemolysis: Cola-colored urine (hemoglobinuria), hemolytic anemia
  • Thrombosis: Symptoms are determined by where the clot occurs. If the clot is located in a vein of the liver, there may be jaundice and an enlarged liver. In the abdomen, a clot would cause abdominal pain; in the head, a headache. Clots in the skin cause raised, painful, red lumps over large areas of the skin, such as the back.
  • Deficient hematopoiesis: Anemia (not enough red blood cells), susceptibility to infections (not enough white blood cells), and abnormal bleeding (not enough platelets).

Causes

PNH is caused by a gene mutation in the PIGA gene, but it is not an inherited disease. The gene occurs randomly in a single stem cell, which then multiples and expands, causing the disease. The reason why PNH cells expand and multiply is not fully understood, but a likely cause is that bone marrow failure due to an autoimmune response is at the heart of it—which is why PNH occurs in most cases of acquired aplastic anemia.

Diagnosis

There are several laboratory tests that can help diagnose paroxysmal nocturnal hemoglobinuria. The most precise is testing the blood to detect two proteins—CD55 and CD59. Absence of these proteins on red blood cells confirms the diagnosis of PNH. During diagnosis, other blood tests will be done including a complete blood cell count (CBC), reticulocyte count, serum lactate dehydrogenase (LDH), bilirubin, and haptoglobin. A bone marrow sample (biopsy) may be taken and examined under a microscope.

Treatment

Treatment of PNH is based upon which symptoms are present. Many adults are treated with steroids (prednisone) daily when hemolysis occurs and changed to alternate days during remission. Iron and folic acid supplements help replace losses due to hemolysis. Some individuals may receive androgenic hormones to stimulate red blood cell production. In severe anemia, a blood transfusion may be necessary. Blood thinners may be used to reduce the development of blood clots. Deficient hematopoiesis may be treated with antithymocyte globulin (ATG).

Drugs that are used to control PNH include:

  • Soliris(eculizumab): Studies have shown that treatment with eculizumab produced a dramatic reduction in hemolysis, and a reduction in days per month of hemoglobinuria.
  • Antithymocyte globulin (ATG) and cyclosporine: These are immunosuppressant medications used to keep the immune system from attacking the bone marrow.
  • Ultomiris (ravulizumab-cwvz) is a long-acting C5 inhibitor that works by inhibiting the C5 protein.

A bone marrow (stem cell) transplant, in which your stem cells are replaced with healthy ones from a matched donor, is the only potential cure for PNH. Nearly all people with PNH will eventually require a transplant in order to live longer.

A Word From Verywell

While living with paroxysmal nocturnal hemoglobinuria can be frightening, there are more treatments than ever before that are increasing life expectancy—and research on the disease continues.

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