Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease that causes red blood cells to break apart. Doctors call this breaking apart "hemolysis." It happens because the surface of a person’s blood cells are missing a protein that protects them from the body's immune system.
When red blood cells break apart, the hemoglobin inside is released. Hemoglobin is the red part of red blood cells that carries oxygen around the body. The release of hemoglobin causes many of the PNH symptoms.
PNH can appear at any age and in any race or gender but is diagnosed most often in people in their 30s and 40s. Experts estimate between 400 and 500 cases are diagnosed in the U.S. each year.
To understand PNH, you must first learn how your immune system works, and how your bone marrow makes blood. This section defines the process and explains what goes wrong when you get PNH.
What does the name mean?
The name paroxysmal nocturnal hemoglobinuria comes from:
- Paroxysmal - means "sudden and irregular"
- Nocturnal - means "at night"
- Hemoglobinuria - means "hemoglobin in urine"; hemoglobin, the red part of red blood cells, makes urine look dark
So, "paroxysmal nocturnal hemoglobinuria" means sudden, irregular episodes of passing dark colored urine, especially at night or in the early morning. It is important to note this can be a bit misleading, because many people with PNH do not have dark urine.
Blood consists of blood cells floating in plasma. Plasma is mostly made of water. It also includes salts, proteins, hormones, minerals, vitamins and other nutrients and chemicals your body needs.
What are the 3 Basic Types of Blood Cells?
- Red blood cells (RBCs) are also called erythrocytes. They make up almost half of blood. Red blood cells are filled with the protein hemoglobin that picks up oxygen in the lungs and brings it to cells all around the body.
- White blood cells (WBCs) are also called leukocytes. They fight disease and infection by attacking and killing germs that get into the body. There are several kinds of white blood cells, each of which fights a different kind of germ.
- Platelets are also called thrombocytes. They are small pieces of cells that help blood clot and stop bleeding.
How are Blood Cells Formed?
The process of making blood cells is called hematopoiesis. Blood cells are made in the bone marrow, a spongy tissue located inside certain bones. Marrow contains blood-forming stem cells that make copies of themselves to create all 3 types of blood cells. When blood cells are fully mature and functional, they leave the bone marrow and enter the bloodstream. Healthy people have enough stem cells to make all the blood cells they need.
What is Bone Marrow Failure?
Bone marrow failure happens when the marrow does not produce enough red cells, white cells or platelets, or the blood cells that are produced are damaged or defective. This means the body can not supply itself with the blood it needs. PNH, along with aplastic anemia and MDS, are bone marrow failure diseases.
The Complement System
The complement system is a group of proteins in the blood. They help support (complement) the work of white blood cells by fighting infections.
These proteins are always active at a very low level. But when bacteria, viruses and other foreign or abnormal cells get into your body, these proteins become more active. They work together to attack and destroy these abnormal cells.
Normal red blood cells have a shield of proteins. This shield protects the cells from being attacked by the complement system. The gene in charge of making this protective shield is called PIG-A.
PIG-A Gene Mutation
- The abnormal stem cell makes copies of or "clones" itself. This leads to a whole population of bone marrow stem cells that have mutant PIG-A.
- The abnormal cells mature into red blood cells that have mutant PIG-A. These are called PNH red blood cells. Doctors also call them your PNH clone.
- The PNH red blood cells lack the shield of proteins that protect normal red blood cells from the complement system, leaving them open to attack and destruction by the complement system proteins.
Many healthy people have a small number of PNH stem cells. In people with PNH, however, these stem cells grow fast and make lots of mature PNH red blood cells.
Some doctors believe this growth happens because people with PNH have bone marrow that is weaker than normal. This weakening may be caused by aplastic anemia or another mild and/or undiagnosed bone marrow failure disease.
Impact of PNH
The course and impact of PNH varies a lot from person to person. You may have only mild symptoms, or you may have severe symptoms and need medicines or blood transfusions.
Many people with PNH live for decades. People who develop blood clots in key parts of the body, or also have MDS (myelodysplastic syndromes) or AML (acute myeloid leukemia), may have a shorter lifespan.
The good news is that good treatments are available, and new treatments are being developed that help people with PNH live longer. You may have seen older research saying that patients with PNH live an average of 15 to 20 years, but more recent research shows that life expectancy has been steadily climbing over the past 20 years. It is even possible that PNH patients will soon live just as long as the average person of the same age.
PNH Risk Factors
Having aplastic anemia is the only known risk factor for developing PNH. More than 10 out of every 100 people with aplastic anemia will develop PNH. In addition, some people with PNH will develop aplastic anemia. People with PNH can share symptoms with aplastic anemia patients, such as low blood cell counts.
On average, 2 out of 100 people with PNH go on to develop myelodysplastic syndrome (MDS).