Paroxysmal nocturnal hemoglobinuria (PNH), a condition in which your red blood cells are destroyed, is usually diagnosed based on the results of a combination of tests. Each of these tests may tell your doctor something different about an aspect of your health and make it clear if you’re living with this rare disease.

1. Tests To Look for Signs of PNH

Your doctor may suspect you have PNH if you experience common symptoms such as dark-colored urine (particularly after sleeping), abdominal pain, and jaundice (yellowing of the skin or whites of the eyes). During a physical exam, your doctor may ask you about your symptoms and your medical history. This information can provide clues that you’re dealing with a blood disorder.

One of the first signs of PNH may be abnormalities in your complete blood count results that show you have anemia (low levels of red blood cells).

Additionally, routine blood work may produce abnormal test results that could signal PNH. The following tests measure levels of certain cells or substances in the blood and can indicate if there’s an abnormality. All of these tests use a blood sample.

Complete Blood Count

A complete blood count (CBC) analyzes how many blood cells you have. It counts the number of blood cells, including red blood cells, white blood cells, and platelets, as well as other substances in your blood like hemoglobin.

One of the first signs of PNH may be abnormalities in your CBC results that show you have anemia (low levels of red blood cells). Getting a CBC can also help you understand whether your PNH is causing problems with other types of blood cells. Some people with PNH have low white blood cell counts or low platelet counts, which can cause additional symptoms.

Reticulocyte Count

Reticulocytes are immature red blood cells. They are made in your bone marrow (the spongy tissue found inside certain bones) by hematopoietic stem cells (the cells that create all of your blood cells). Once reticulocytes are produced, they enter your bloodstream and then turn into normal red blood cells after a couple of days.

You could have a high reticulocyte count if you have PNH. This happens because your body is trying to make many new red blood cells to replace the ones that were lost.

Haptoglobin Test

Haptoglobin is a protein that attaches to any hemoglobin proteins that enter your bloodstream. Your body clears out haptoglobin proteins that are joined with hemoglobin.

When red blood cells break apart, they release hemoglobin into your bloodstream. Haptoglobin binds to the hemoglobin, helping your body clear it out more quickly than your liver can replace the haptoglobin. Therefore, low haptoglobin levels can be a sign of a red blood cell disorder such as PNH.

Bilirubin Test

As your body breaks down red blood cells, bilirubin is produced. This yellowish pigment is usually cleared out of the body by your liver. However, if your red blood cells are being destroyed too quickly, your liver may not be able to keep up. High bilirubin levels can be another sign of hemolysis (the destruction of red blood cells).

Lactate Dehydrogenase Test

This blood test measures levels of lactate dehydrogenase (LDH) in your blood. LDH is an enzyme (protein) that helps make energy for your cells.

High LDH levels can result from red blood cell breakdown, which may be caused by PNH. However, LDH can also be a sign of damage in other tissues, such as your heart, brain, lungs, or kidneys.

You may need ongoing LDH tests if you’re diagnosed with PNH. Because LDH levels rise as more red blood cells break open, this test can help your doctor determine whether a treatment is working or find out if your condition is getting worse.

2. Tests To Confirm PNH

Blood tests can tell you when something is wrong. However, they don’t always point out the exact cause. Additional laboratory tests can help determine exactly what’s happening with your blood cells and answer the question, “Do I have PNH?”

Flow cytometry, also called immunophenotyping, is considered the gold standard test for confirming a diagnosis of PNH.

Flow Cytometry

Flow cytometry, also called immunophenotyping, is considered the gold standard test for confirming a diagnosis of PNH. In other words, it is the single most important paroxysmal nocturnal hemoglobinuria diagnostic test. This test can be completed using a small blood sample. During flow cytometry, a machine analyzes blood cells one at a time to look for certain proteins found on the surface of the cell.

Healthy red blood cells contain a protein “shield.” This shield protects the red blood cells from the immune system, which works to find and eliminate any foreign cells or substances that could harm your body. The anchored protein shield around a red blood cell tells your immune system that the cell is safe. However, PNH cells lack this shield and are destroyed.

Flow cytometry detects red cells and granulocytes (a type of white blood cell) that lack these proteins, called PNH clones. If flow cytometry shows that your blood cells have few or none of the proteins that make up the shield, you may receive a PNH diagnosis. If you’re diagnosed with PNH, you may undergo regular flow cytometry testing to help manage your condition and monitor any treatment progress.

Bone Marrow Biopsy and Testing

A bone marrow test can’t confirm PNH, but it is used to check for closely related bone marrow disorders that often accompany PNH. One of the causes of PNH involves problems with stem cells in your bone marrow. When these stem cells develop a mutation in the gene called PIGA, they don’t make enough healthy blood cells. This is known as bone marrow failure.

To diagnose bone marrow failure associated with PNH, your healthcare team can perform a trephine biopsy, which involves removing a small sample of your bone marrow for study. This helps them check for gene changes and abnormal growth, as well as whether your bone marrow is producing the right number of blood cells.

A bone marrow test helps your doctor get a full picture of any related conditions and helps diagnose conditions similar to PNH, such as aplastic anemia or myelodysplastic syndrome (MDS), which often cause bone marrow failure in people with PNH. It’s possible to have more than one bone marrow disorder at the same time.

Doctors generally remove a sample of bone marrow cells from either your pelvic bone or your breastbone. When collecting the sample, they will first numb the area and then insert a long needle into the bone to reach the marrow.

3. Tests To Distinguish PNH From Other Conditions

Signs and symptoms of PNH can mimic those of other disorders. For example, multiple types of hemolytic anemia can cause your red blood cells to break apart. Many of these conditions lead to the same results on blood tests, such as low red cell counts, high bilirubin levels, and high amounts of LDH in your blood.

Some signs and symptoms of PNH can mimic those of other disorders.

Your doctor may recommend tests to look for other potential causes of anemia. These tests can include:

• Iron test or ferritin test — This test measures iron levels in your body, as having too little of this mineral is a common cause of anemia.
• Vitamin B12 or folate (vitamin B9) tests — These tests can help determine other causes of low red blood cell levels, as a vitamin deficiency may also lead to abnormal blood cells.
• Erythropoietin (EPO) test — This test detects low levels of EPO, a hormone that helps your body make red blood cells, which may be a sign that other problems are responsible for anemia.
• Coombs test — This blood test helps differentiate PNH from other, more common causes of hemolytic anemia.

Talk to your doctor if you’re experiencing any health changes. Your provider can conduct a PNH assessment using a range of tests and recommend appropriate PNH treatment options to improve your quality of life.

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