PNH, or Paroxysmal nocturnal hemoglobinuria, 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 PNH 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.
What happens to my blood with PNH?
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.
What is the complement system in PNH?
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.
What is PIG-A gene mutation?
PNH occurs because of a genetic change (mutation) in the PIG-A gene of a single stem cell in your bone marrow. Here are the steps that lead to PNH:
- 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.
What happens to someone with PNH?
The course and impact of PNH may vary 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.
What are the risk factors of having PNH?
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).
Consulting a PNH Expert and Getting a Second Opinion
A PNH diagnosis is complicated and the treatment options require a well-trained and experienced PNH expert. AAMDSIF has a small grant fund available for PNH patients to see a PNH expert or to get a second opinion from a PNH expert. For more information about this fund and to submit an application, please click here.
Special Precautions for PNH Patients
Because you have PNH, everyday events can be more risky for you than for healthy people. Here are some special precautions you can take to stay safe and healthy.
Airplane Travel and High Altitudes
The farther you move away from sea level, the less oxygen there is. If you have anemia, flying in an airplane or visiting places at higher elevations than you’re used to may cause a shortage of oxygen. It may also cause chest pain. Before you do either of these things, it's a good idea to:
- Check with your doctor
- Get a red blood cell count
- Get treatment for your anemia (blood transfusions or growth factors)
- If you do fly, remember to:
- Drink plenty of water
- Get up and walk around every hour or two if it is safe to do so
What immunizations should a PNH patient get?
Patients with PNH should receive vaccinations against certain types of bacteria to prevent infection. Ask your doctor which ones are right for you.
Seasonal flu vaccines protect against the three influenza viruses (trivalent) that research indicates will be most common during the upcoming season. Talk with your hematologist about whether you should get a flu shot. He will help you weigh the risks and benefits of getting a flu shot. Don’t forget to ask whether your family members and others in close contact with you should get a flu vaccine. This may reduce your chance of getting the flu. To read more about flu shots, read our article.
There have been a few case reports of PNH patients getting flares of hemolysis (when red blood cells are destroyed) after receiving a flu shot. Although case reports are not the same as randomized clinical trials, one case of hemolysis was severe enough to put the patient in the hospital. That is why some PNH experts recommend against having a flu shot, but each case is different. PNH patients who are receiving eculizumab may be less likely to have hemolysis after receiving a flu shot.
Can PNH patients get pregnant and have a healthy delivery?
Pregnancy is possible with PNH, but it is not a good idea. It carries serious risks for both mother and child.
A woman with PNH faces a number of risks during pregnancy:
- Her blood may have fewer healthy cells.
- Her bone marrow may make fewer healthy cells.
- She is more likely to get blood clots. Most doctors place pregnant women with PNH on blood thinners to prevent clots. But warfarin (Coumadin®) cannot be used during the first trimester, since it may affect fetus development.
- She is more likely to get preeclampsia, a dangerous condition that causes very high blood pressure and can put both mother and baby at risk.
- She may need red blood cell transfusions more often.
A baby whose mother has PNH has a greater risk of:
- Premature birth
- Dying in the womb
- Having a low birth weight
- Having delayed growth and development
Still, about 1 out of 3 babies whose mothers have PNH do not have any of these problems.
If you do get pregnant, look for a PNH specialist and an OB (obstetrician) who specializes in high-risk births.
Is surgery safe for PNH patients?
Surgery can also be risky for people with PNH because it:
- Makes the complement system more active, which can cause hemolysis
- Increases the risk of getting blood clots
- Can cause serious bleeding in people with a low platelet count
- May require platelet transfusions before surgery.
If you do have surgery, it is a good idea to:
- Make sure your PNH specialist talks with your surgeon
- Take the blood thinner Heparin (Calciparine® or Liquaemin®) as soon as possible after surgery, as long as your platelet count is good and your doctor advises it.