Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder named for a single symptom: Red/brown/dark urine noticed during late-night or early morning trips to the bathroom.

“Paroxysmal” means sudden; “nocturnal” means night; and “hemoglobinuria” refers to pee stained with blood. Your pee is dark because your immune system is breaking down your red blood cells. Healthcare providers call this hemolysis.

Dark-colored pee is only one of many symptoms that may signal potentially serious illnesses. Left untreated, PNH may cause hemolytic anemia, chronic kidney disease or thrombosis (blood clots in your blood vessels). 

Healthcare providers treat PNH with medication that prevents blood cell damage.

Symptoms of PNH

Although paroxysmal nocturnal hemoglobinuria gets its name from the dark-colored pee, people typically seek help because of a different symptom: extreme tiredness (fatigue). Also, not everyone has dark-colored pee. If you do, the color changes may be noticeable at any time, not just in the morning or at night.

Other symptoms include:

• Shortness of breath
• Kidney problems
• Trouble swallowing
• Esophageal spasms
• Pain in your back, chest or stomach
• Erectile dysfunction

Symptoms range from mild to severe. Sometimes, they don’t start until a trigger event, like an infection, stresses your body.

​Paroxysmal nocturnal hemoglobinuria causes

PNH happens when you develop a flaw in the PIGA gene. It’s not a flaw you’re born with. Instead, you develop it during your lifetime. Experts are still researching to understand why.

The PIGA gene makes proteins that create a protective shield around your red blood cells. This shield protects red blood cells from a network of circulating proteins in your blood that can harm them. Experts call these proteins the complement system.

But with PNH, the faulty gene can no longer make the protective shield. Here’s what happens next:

1. Your complement system attacks your red blood cells that lack protection. As a result, they fall apart and release hemoglobin into your bloodstream. The hemoglobin is what changes the color of your pee. The excess hemoglobin in your blood can also strain your kidneys.
2. Substances in your body work to clear out the excess hemoglobin. One of these substances is nitric oxide. But the extra work can use up your body’s supply of it. Too little nitric oxide can cause painful spasms in your esophagus, stomach or back.
3. This cascade of changes triggers your platelets to make extra clots. The clotting can be serious. Serious clots are the leading cause of death in PNH.

The premature destruction of your red blood cells can lead to anemia. All the clotting can use up too many of your platelets.

Risk factors

Only about 1 in 1 million people get this diagnosis each year. It can affect people of all ages, but it’s most common in adults in their 30s and 40s.

Your risk is greater if you have a disorder like aplastic anemia or myelodysplastic syndrome (MDS). These conditions interfere with your body’s ability to make enough healthy blood cells. More than 10 out of every 100 people with aplastic anemia develop paroxysmal nocturnal hemoglobinuria. 

Complications of this condition

Just like people with aplastic anemia and MDS can develop PNH, the opposite can also be true. You can have PNH first and then develop these conditions.

Blood clots (thrombosis) are a major complication of PNH. The most common types of thrombosis that happen with this condition involve your:

• Liver, as in hepatic thrombosis
• Abdomen, as in abdominal vein thrombosis
• Brain, as in cerebral thrombosis
• Skin, as in dermal thrombosis

Many of these complications can cause serious organ damage. They can be life-threatening without treatment.

How doctors diagnose this condition

Healthcare providers may use several tests to look for signs of PNH. Based on those test results, they’ll use a test called flow cytometry to check your blood cells.

You may also need:

• Lab tests to check for issues with your blood cells or organ function
• Imaging tests to show signs of clots or bleeding 
• Bone marrow biopsy to see if PNH is happening as a result of another condition that affects your blood cells, like aplastic anemia and MDS

Tests that are used

Lab tests are key to a PNH diagnosis. Your healthcare providers may run the following tests:

• Complete blood count with differential: Healthcare providers check for low blood cell counts and high levels of immature red blood cells.
• Basic metabolic panel: Healthcare providers look for signs of chronic kidney disease.
• Urinalysis: This test may show signs of blood in your pee and excess iron (from the hemoglobin).
• Haptoglobin test: Haptoglobin is a protein that gets rid of debris from damaged red blood cells. Low levels may be a sign of damaged red blood cells.
• Lactate dehydrogenase (LDH): LDH is an enzyme in red blood cells. A high LDH level may be a sign of increased red blood cell destruction.
• Liver function: This test measures bilirubin levels. Bilirubin is a waste product of red blood cells. Levels increase when lots of red blood cells break down.

How is it treated?

Healthcare providers use medicines called complement inhibitors to keep your complement system from destroying red blood cells. Most involve getting regular IV blood transfusion infusions or injections. Some come in pill form. These medicines help most people living with PNH manage it.

If you have a severe episode of anemia, you may need a red blood cell transfusion. If you have clots, you may need blood thinners. But most people with this condition don’t need these treatments long term.

The only cure for PNH is an allogeneic stem cell transplant. With this procedure, you get high-dose chemotherapy that destroys the abnormal blood cells. Then, you get an infusion of healthy blood cells from a donor to replace them.

Finding a donor with a compatible blood type isn’t always possible. And this treatment comes with high risks. But your provider may recommend it if complement inhibitors aren’t helping enough.

When should I see my healthcare provider?

Your healthcare provider will check your blood cells regularly to manage the anemia. They’ll run tests to make sure you’re not at risk of a complication.

PNH is a manageable condition, but it’s a serious one. You’ll work closely with your hematologist (blood specialist) to ensure you’re in good health.

What can I expect if I have this condition?

There are treatments that stop PNH from damaging your red blood cells. Complement inhibitors have greatly improved the outlook for people with this condition.

Before this therapy was available, people with paroxysmal nocturnal hemoglobinuria needed regular red blood cell transfusions. Even with regular care, most people usually only lived 10 to 20 years after their diagnosis.

Now, people who receive complement inhibitors can expect to live nearly as long as someone who doesn’t have PNH. In the meantime, your healthcare provider will check on you to help manage symptoms and prevent complications.

Is there anything I can do to feel better?

One of the best things you can do is to know how to work with your healthcare provider to stay in good health.

For instance, you may need treatment to prevent blood loss if you’re having any kind of surgery. It’s important that all your providers know about your condition. They should know how to reach your hematologist.

You may also want to ask your hematologist about:

• How often you need blood tests
• The types of vaccines you should get
• Ways to travel and fly safely (high altitudes involve less oxygen, which can be harmful if your red blood cell counts are low)
• Risks involved in pregnancy (pregnancy can pose health risks to you and the fetus if you have PNH)

What is the difference between hemoglobinuria and hematuria?

Both conditions cause blood in your urine. The difference is that hematuria is red blood cells in your urine, while hemoglobinuria is hemoglobin in your urine. Hemoglobin is a protein in your red blood cells that makes blood look red.