About PNH      Causes      Symptoms    Treatments

About PNH

PNH is a rare and serious blood disease that causes red blood cells to break apart. Doctors call this breaking apart "hemolysis". It happens because your blood cells are missing a protein that protects them from your body's immune system.

When your red blood cells break apart, the hemoglobin inside them is released. Hemoglobin is the red part of red blood cells. Its job is to carry oxygen around your body. The release of hemoglobin causes most PNH symptoms.

Where does the name come from?

Here's where the name "paroxysmal nocturnal hemoglobinuria" comes from:

• Paroxysmal - means "sudden and irregular"
  
• Nocturnal - means "at night"
• Hemoglobinuria - means "hemoglobin in urine"; hemoglobin is the red part of red blood cells - it makes your 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 that many people with PNH do not have dark urine.

What is 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 the abnormal cells in your body.

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 causes PNH?

PNH occurs because of a change (mutation) in the PIG-A gene of a single stem cell in the bone marrow. Here are the steps that lead to PNH:

1. The abnormal stem cell makes copies of or "clones" itself. This leads to a whole population of stem cells that have mutant PIG-A.
2. The abnormal stem cells turn into mature red blood cells that have mutant PIG-A. These are called PNH red blood cells.
3. The PNH red blood cells lack the shield of proteins that protect normal red blood cells from the complement system. So they may be attacked and destroyed by the complement system proteins.

Many healthy people have a small number of stem cells with mutant PIG-A. But in people with PNH, these stem cells grow fast and make lots of mature PNH red blood cells.

Some doctors believe this happens because people with PNH have bone marrow that is weaker than normal. A person's bone marrow may be weakened because they have aplastic anemia or another bone marrow failure disease. Weakened bone marrow may also result from a mild bone marrow disease that was never diagnosed.

What are the symptoms of PNH?

PNH can cause a variety of symptoms. You may have many of these symptoms, or just one or two. And you may experience a new symptom at any point in the course of your illness. Some people have more severe symptoms than others.

The symptoms you have with PNH are caused by one of the following:

• Hemolysis – the breaking apart or destruction of red blood cells
• Thrombosis – blood clots
• Low blood cell count – not having enough of a type of blood cell

Each of these health problems can cause certain symptoms as described below.

Hemolysis

Hemolysis is the breaking apart of red blood cells.

What causes hemolysis?
Hemolysis happens when the complement system becomes more active and attacks your PNH red blood cells. The complement system usually attacks only foreign objects, such as viruses and bacteria. But, because PNH cells are damaged, it sees them as foreign and attacks them too, causing them to burst.

What are the symptoms of hemolysis?
When your PNH red blood cells break apart, their hemoglobin is released into your plasma. Hemoglobin is the red part of red blood cells. Its job is to carry oxygen around your body. The release of hemoglobin can cause a number of symptoms:

• Your urine may get darker; or it may not darken at all
• You may have a low red blood cell count (anemia) which can cause you to:
• Feel very tired
• Have headaches
• Have trouble breathing when you exercise
• Have an irregular heartbeat

What are the symptoms of severe hemolysis?
If you have severe hemolysis, hemoglobin may be quickly released into your bloodstream. This can cause a number of symptoms:

• You may feel very tired.
• The hemoglobin may bind with and remove nitric oxide from your system. Nitric oxide helps your muscles stay smooth and relaxed. A shortage of it can cause muscle spasms in certain parts of your body:

• You may have anything from mild to severe pain in your abdomen or belly area.
• You may have spasms in your esophagus which is a "tube" in your throat that goes from your mouth to your stomach; the spasms can make it hard to swallow.
• Men may have trouble getting or keeping an erection (be impotent).

Thrombosis

Thrombosis is a blood clot in a vein. It is often simply called a blood clot.

Who gets blood clots?

At least 1 out of 3 people with PNH gets blood clots. 

Why are blood clots so common for people with PNH?

Scientists are not sure exactly why people with PNH are more likely to get blood clots. But some believe that PNH patients have abnormal platelets that are too "sticky." This means the platelets make clots too easily.

Plus, many people with PNH have a shortage of nitric oxide. Nitric oxide helps prevent blood clots by making it harder for platelets to stick together. Hemolysis – another symptom of PNH – can cause a shortage of nitric oxide.

What are the symptoms of blood clots?

The symptoms of blood clots depend on where the clots occur. People who are otherwise healthy and don't have PNH sometimes get blood clots in the veins of the leg. But people with PNH tend to get blood clots in other parts of the body, such as in the brain or abdomen (belly area).

Blood clot in abdomen (belly area)

You may get a blood clot in your abdomen, or belly area. That's the area below your chest and above your hips. Here are some places in the abdomen where you may get a blood clot:

• You may get a blood clot in your spleen.
• You may get a blood clot in the major vein that leaves your liver; this is called Budd-Chiari syndrome.
• Your intestine (bowel) may not get enough blood; this is called ischemia.
  

If you have a blood clot in your abdomen:

• You may have fluid and swelling in the belly area; this is called ascites.
• The area where the clot is may feel warm to the touch.
• The area where the clot is may be painful.
  

If the blood clot in your abdomen is not treated:

• Part of your intestine may die (dead bowel)
• Your liver may be damaged and stop working
  

Blood clot in brain

You may get a blood clot in the veins covering your brain. If this happens:

• You may get a very bad headache.
• Your brain may not work as well as usual; you may have trouble speaking, seeing, or moving parts of your body.
  

Blood clot in skin

You may get a blood clot in the veins of your skin. If this happens:

• Your skin in that area may get red, puffy, warm, or painful
  

Blood clot in arm or leg

You may get a blood clot in the veins of your arm or leg. If this happens:

• That limb may get warm, puffy, or painful
  

Blood clot in lung

Sometimes, a blood clot breaks off and travels to your lung. This is called a pulmonary embolism (PULL-muh-nerr-ee EM-buh-liz-um). If you have a pulmonary embolism:

• You may have a sharp pain in your chest; it may get worse when you breathe deeply
• You may have trouble breathing (shortness of breath) or you may start breathing fast
• You may suddenly feel anxious
• You may cough up some blood
• You may feel dizzy; you may even faint
• You may sweat a lot

How do I find out if I have a blood clot?

To diagnose a blood clot, your doctor may take pictures of your insides using:

• CT scan (Cat Scan)
• MRI (Magnetic Resonance Imaging) 
• Doppler scan
• V-Q Scan (Ventilation-Perfusion Scan)
  

Or, your doctor may order a lab test called D-dimer. It's also called Fragment D-Dimer, or Fibrin degradation fragment.

Low Blood Counts

The symptoms of PNH are often caused by low blood cell counts. The symptoms depend on which type of blood cell is affected. For PNH, the most common shortage is red blood cells.

Low Red Blood Cell Count 

A low red blood cell count is called anemia. Red blood cells carry oxygen from your lungs to the rest of your body. A low red blood cell count causes fatigue and tiredness.

Low White Blood Cell Count

A low white blood cell count is called neutropenia. White blood cells fight infections in the body by attacking and killing bacteria and viruses. A low white blood cell count can increase the risk for infections.

Low Platelet Count 

A low platelet count is called thrombocytopenia. Platelets help blood to clot and stop bleeding. A low platelet count can lead to bleeding problems and cause you to bruise easily.

Learn more about the symptoms of low blood counts.

How does my doctor know I have PNH?

PNH is a rare disease. Many doctors have never seen a case of it. So people with PNH may have symptoms for several years before they get a correct diagnosis.

3 Types of Blood Cells

With PNH, your doctor can usually divide your blood cells into 3 types:

1. PNH I cells, or Type I cells: These cells respond in a healthy way to the complement system. They are normal cells.
2. PNH II cells, or Type II cells: These cells are partially sensitive to the complement system. They are missing some of the proteins that protect them from attack.
3. PNH III cells, or Type III cells: These cells are extremely sensitive to the complement system. Of the 3 groups of cells, these ones break apart most easily. They are missing all the proteins that protect normal cells from attack. 
   
   Most people with PNH have mostly Type I and Type III cells. But the amount of each type of cell can vary greatly.

How did my doctor classify my blood cells into these 3 groups?

Your doctor probably used a flow cytometry test. This test lets your doctor see if any proteins were missing from your red blood cells. It can also be done on certain white blood cells called granulocytes.

FLAER is a new type of flow cytometry test.

You may have heard of a test called "Ham's test" that was used in the past to check for PNH. Because this test does not give correct results, it is no longer used.

What other tests may I get?

Your doctor may ask you to get other lab tests as well. These include:

• CBC (complete blood count)
• Ferritin test to check your iron levels 
• Tests of your solid bone marrow (through a bone marrow biopsy)

Your doctor may also look for high levels of:

• A pigment called bilirubin
• An enzyme called LDH (lactate dehydrogenase)
• Young red blood cells in your bone marrow