- A acquired deficiency in the PIGA gene alters red blood cells.
- Paroxysmal nocturnal hemoglobinuria results when these altered cells replicate.
- Medications can stop the breakdown of red blood cells and reduce the risk of anemia, blood clots, and other effects of the condition.
Paroxysmal nocturnal hemoglobinuria (PNH) is a condition where red blood cells break open. The contents of those cells circulate in the bloodstream.
PNH is linked to a difference in the phosphatidylinositol glycan anchor biosynthesis class A (PIGA) gene. The action of this gene creates a group of red blood cells that are vulnerable to breaking or damage.
PNH has many serious effects, but newer treatments have improved the outlook for people with the condition.
The PIGA gene
The PIGA gene difference is a somatic mutation. This means it’s not inherited. The gene change happens spontaneously during one’s life.
The PIGA deficiency causes PNH through a process where several cells are affected. This starts with a single stem cell in bone marrow that carries the gene difference.
If a person has PNH, this stem cell makes copies of itself. The result is several bone marrow stem cells with the altered PIGA gene. These cells become red blood cells, called PNH red blood cells.
PNH red blood cells don’t have enough protective proteins. The body’s other systems, specifically those that support the work of the white blood cells in fighting infections, can then attack the surface of these cells. This leads to their damage and destruction.
Developing PNH requires at least two factors: a blood stem cell that carries the PIGA gene difference that creates the PNH blood cells and a process for those cells to expand and multiply.
Researchers don’t know why, in some people, the PNH blood cells expand and multiply. It’s this process that ultimately causes the signs and symptoms of PNH.
The destruction of red blood cells can lead to a number of symptoms and conditions. While some people have mild symptoms, others are more severe.
Some of the more severe effects of red blood cell destruction include:
- hemoglobin (red blood cell protein) in the urine, sometimes causing red-colored urine
- hemolytic anemia, where the body can’t make enough red blood cells to keep up with those lost to damage
- bone marrow dysfunction
- blood clots
- kidney disease
Some of the signs of hemolytic anemia include:
- rapid heart rate
- chest pain
- breathing problems
If the anemia progresses, it can also cause:
- severe fatigue
- difficult swallowing
- abdominal contractions
- esophageal spasms
- erectile dysfunction
Because many of the signs of PNH are not specific to this condition, it can take a
To test for PNH, doctors use a process called flow cytometry to
There are low- and high-sensitivity tests for PNH. The low-sensitivity test is enough to diagnose PNH, but a high-sensitivity test can also help identify an additional condition such as a bone marrow disorder that can be present at the same time as PNH.
The cornerstone treatments for PNH are the medications eculizumab and ravulizumab. Both medications work to prevent the breakdown of red blood cells. They do this by stopping the body’s system that attacks the vulnerable PNH blood cells. The drugs don’t replace or compensate for the lack of proteins on the PNH cells themselves.
Eculizumab follows a dosing schedule of once every two weeks, while ravulizumab is every eight weeks.
A doctor may also recommend supplementary therapies for someone with PNH. These might include:
- folic acid (folate) supplementation
- iron supplementation
- steroids (prednisone) to slow red blood cell destruction
- anti-coagulation therapy to prevent blood clots
- immunosuppressive therapy
- blood transfusions to correct anemia and prevent bleeding
- growth factors or hormones to promote blood cell production
In severe cases of PNH, some people may also receive a bone marrow transplant. Because this is a high risk procedure, it’s only recommended for those with serious symptoms from PNH.
Paroxysmal nocturnal hemoglobinuria (PNH) is marked by the vulnerability of red blood cells to attack. The lack of protective proteins on PNH cells is the result of a difference in the PIGA gene. One blood stem cell with the PIGA gene difference multiplies and those cells become PNH cells.
Tests for PNH include blood cell analysis. Genetic testing for PIGA differences may also be possible but aren’t widely available.
Treatment for PNH has had a few notable advancements. The drugs eculizumab and ravulizumab have made it possible for people with PNH to have an improved quality of life.