Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder that causes red blood cells to break down sooner than they should. The results of this premature destruction can lead to symptoms and complications that range from minimal (such as discoloration of urine) to severe (such as leukemia and stroke). There are no known risk factors for PNH, and although it involves a gene (PIG-A), it is not a disease you can inherit from your parents.
A variety of treatments can alleviate symptoms PNH. Medications to treat the symptoms of PNH are often adequate, but in more severe cases of the disease, blood transfusions or steroid treatment may be necessary. The outlook for a PNH diagnosis is highly variable, with some living from a few to up to ten years longer with treatments.
PNH is an acquired disease that involves a gene called PIG-A. Although it has this genetic component, you cannot inherit PNH. The disease is acquired through genetic mutations that occur throughout your life.
When mutations lead to the loss of the PIG-A gene, the result is PNH. The mutations happen in hematopoietic stem cells. These cells are found in your bone marrow and lead to the production of blood cells. With the acquired mutation, you create abnormal blood cells.
The loss of the PIG-A gene means that you lack a protective protein layer on the outside of your red blood cells. In normal cells, this layer of proteins signals to your immune system that the red blood cells are not foreign and should not be destroyed. When you lack these proteins, your red blood cells are dismantled sooner than they should be. If you have PNH, your number of blood platelets, which are responsible for blood clotting, may be decreased and their function impaired.
The primary symptom of PNH is discolored urine. When your red blood cells are destroyed prematurely, hemoglobin (the compound that makes your blood red) is released in your urine. The discoloration is usually seen at night or early in the morning, after urine has accumulated in the bladder. Some people with PNH, however, will not see a discoloration. Hemoglobin may be present in the urine at levels that are not detectable by sight.
Other symptoms of having PNH include:
- back pain
- shortness of breath
- abdominal pain
- easy bruising
A very serious possible side effect of PNH is the formation of blood clots. The clots result from the effect the disease has on blood platelets, which are involved in the clotting of blood. Symptoms of PNH can vary widely from person to person. Some people will only experience very mild symptoms, while others may experience severe and life-threatening complications.
The lack of the PIG-A gene can lead to a host of illnesses and complications that range from minor to life threatening.
Anemia is a condition that arises from having too few red blood cells and is very common with PNH. There can be various causes, but in the case of PNH, it occurs because of the premature destruction of blood cells. Symptoms include feeling tired and weak and having headaches. It can also lead to lightheadedness, pale skin, and shortness of breath.
Acute Myeloid Leukemia
Less commonly, PNH can lead to acute myeloid leukemia the symptoms of which include:
- shortness of breath
- weight loss
- skin rashes
- bone pain
The most serious possible complication, although not as common as anemia, is the formation of blood clots. This complication is called thrombosis. Clots cause pain and soreness where they form in the body. They can also move throughout the body—when in the lungs, brain, or near the heart, they can result in stroke and death.
To diagnose PNH, your doctor will consider your symptoms. The discoloration of the urine is a major clue, as are unexplained blood clots and anemia, but you will likely need more tests to confirm the presence of the disease.
There are several tests that can confirm the disease, but according to the National Center for Biotechnology Information, the best current test is a flow cytometry analysis of red blood cells (Risitano, et al., 2008). The test is very sensitive and can detect the absence of the protein layer on red blood cells that is characteristic of PNH. To have the test, you simply need to have a small sample of blood drawn.
Treatment options for PNH vary depending upon the symptoms you experience and their severity. For most people, PNH can be managed successfully by treating the symptoms. Medications that treat anemia minimize the breakdown of blood cells, and reduce the risk of blood clot formation, which lessens symptoms. Blood transfusions may be necessary to increase the red blood cell count.
You may require steroids to suppress your immune system as part of the disease management. In this event, your doctor may recommend vaccines to keep you safe from infections. You may also need blood transfusions to keep your blood cell levels normal.
A drug called eculizumab can be very effective in some patients. It stops the breakdown of the red blood cells and may replace the need for blood transfusions.
The prognosis for having PNH varies depending on the patient. In very few cases, the abnormal blood cells will actually decrease over time. In most cases, however, treatment is required to manage the disease. Most patients live 10 years or more after the initial diagnosis.