- Paroxysmal nocturnal hemoglobinuria leaves red blood cells more vulnerable to destruction.
- A common side effect is blood clots, known as thrombosis.
- This is largely preventable with medication to treat paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease in which your red blood cells are missing a protective surface protein.
As a result, the red blood cells aren’t durable enough and break apart when they encounter immune system cells. This releases hemoglobin into the bloodstream, raising the risk of clots.
PNH can cause a range of symptoms, which may be mild for some people. It can sometimes occur with conditions like myelodysplastic syndromes (MDS) or aplastic anemia.
One of the most common side effects of paroxysmal nocturnal hemoglobinuria is blood clotting (thrombosis). This is a potentially serious development, but it’s preventable with medication.
Thrombosis causes an estimated
More research is needed to fully clarify the cause of thrombosis in PNH. The lack of a surface protein in red blood cells means that when they break up, they release hemoglobin, causing clots.
It’s thought that the mutation that alters red blood cells also affects the surface protein in platelet cells, which can break up, releasing microparticles that can cause clots.
Chronic hemolysis (cell breakage) may also cause thrombosis.
The risk of thromboembolism from PNH varies by ethnic group in the United States:
|Ethnic group||Rate of PNH thromboembolism|
|Race||Cases of VTE per 1,000|
A variant in thrombomodulin (THBD) gene expression in the African American population may explain the increased rates of VTE in this community, according to
Even though a genetic factor is the cause of PNH, it’s not something you can inherit from your parents. Instead, PNH is the result of a gene mutation that occurs after you’re born. It’s random and starts in a single damaged stem cell that makes multiple copies of itself.
The gene that mutates is called phosphatidylinositol glycan biosynthesis class A protein (PIGA). This gene is responsible for making the proteins on the cell surface that keep blood cells held together in one piece.
When a mutation interferes with the action of PIGA, this can cause red blood cells to form without protective surface layer proteins.
Without these proteins, blood cells don’t last as long as they should. When they encounter certain immune system cells, they break apart. Hemoglobin is distributed into blood plasma and ends up secreted in your urine.
A common complication of PNH is aplastic anemia. This is a condition that prevents your bone marrow from making enough red blood cells. The most common cause is an autoimmune interaction with your bone marrow stem cells. Other causes include radiation and chemotherapy treatments.
Another complication is Budd-Chiari syndrome. This is a condition in which the veins that drain the liver become blocked by blood clots, causing the liver to become larger. Any disorder that increases the likelihood of blood clots can cause Budd-Chiari syndrome.
Blood clots require medical intervention. If you have PNH, it’s important to remember your increased risk for thrombosis so that you can get the care you need.
Possible signs include:
- abdominal pain
- full or bloated feeling
- problems thinking
- shortness of breath
- chest pain
- breathing difficulties
- coughing, with or without blood
- heart palpitations
- limb swelling
- cramp-like or throbbing pain
- skin discoloration
- pitting edema
- painful or swollen veins
If you have signs of a blood clot, seek immediate medical attention to avoid a serious complication.
Eculizumab (Soliris) and ravulizumab (ultomiris) are medications that suppress the action of the complement system. This is the part of the immune system that breaks open the red blood cells affected by PNH.
By suppressing the complement system, this medication reduces the number of broken cells, and in turn, lowers the risk of thrombosis.
Other PNH management strategies include:
- folic acid supplements, to ensure an adequate supply of folate
- steroids, such as prednisone, to slow blood cell damage
- anticoagulant medication, to reduce blood clots
- thrombolytic therapy, to break down existing clots
- immunosuppressive therapy, to restore bone marrow function
- blood transfusions, to increase blood cell counts
- synthetic growth factors or androgens, to stimulate bone marrow cell production
There’s only one cure for PNH: a bone marrow transplant. Because of the risks associated with transplantation, it’s reserved for people with serious complications of PNH.
PNH is a rare but serious blood disorder. It’s caused by a gene mutation that changes the way your bone marrow makes red blood cells, leaving them vulnerable to damage from your immune system.
Thrombosis is the most common serious side effect of PNH. It’s preventable with medication that reduces the chance of cell damage from the immune system.
People of African descent have a higher chance of developing thrombosis, from PNH as well as other causes. This is because of a variation in thrombomodulin (THBD) gene expression.
There are various treatments available for PNH that reduce the chance of serious complications. Bone marrow transplantation is the only cure.
Thrombosis can be life threatening. If you have PNH and experience the signs of a blood clot, it’s important to seek immediate medical assistance.