Paroxysmal nocturnal hemoglobinuria (PNH), a condition in which your red blood cells are destroyed, is diagnosed based on the results of multiple tests. Each of these tests may tell your doctor something different about a facet of your health.

Tests To Look for Signs of PNH

Your doctor may suspect you have PNH if you experience common symptoms such as dark-colored urine, 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.

Additionally, routine blood work may produce abnormal results that could signal PNH. The following tests measure levels of certain cells or substances in the blood and can indicate if there’s a problem. These tests can all be completed by taking 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 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 or 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 created, 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 hemoglobin is released in your blood because your red blood cells are breaking open, haptoglobin will attach to these proteins and be quickly cleared out of your system. Therefore, low haptoglobin levels can be a sign of hemolysis (the destruction of red blood cells) and 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 an additional sign of hemolysis.

Lactate Dehydrogenase Test

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

High LDH levels can occur due to red blood cell destruction and may be triggered 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 get a diagnosis of 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.

Tests To Confirm PNH

Blood tests can indicate when something is wrong. However, they don’t always point out the exact cause. Additional diagnostic tests can help determine exactly what’s happening with your blood cells and confirm or rule out PNH.

Flow Cytometry

Flow cytometry is the most important test during PNH diagnosis. 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 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.

Your health care team can use flow cytometry to look for the presence or absence of these proteins. If this test shows that your red blood cells have few or none of the proteins that make up the shield, you may be diagnosed with PNH.

Bone Marrow Biopsy and Testing

One of the causes of PNH involves problems with stem cells in your bone marrow. When these stem cells develop genetic mutations, they don’t make enough healthy blood cells. This is known as bone marrow failure. Your health care team can biopsy (remove a sample of) your bone marrow and study the cells to see if they contain gene changes, grow abnormally, or produce normal numbers of blood cells.

A bone marrow test helps your doctor confirm whether you have PNH. It also allows them to diagnose conditions similar to PNH, such as aplastic anemia or myelodysplastic syndrome, which often cause bone marrow failure in people with PNH.

Doctors generally remove a sample of bone marrow cells from either your pelvic bone or your breast bone. When collecting the sample, they will first numb the area and then place a long needle through your bone into the inner area where your bone marrow is located.

Distinguishing Between PNH and 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 blood cell counts, high bilirubin levels, and high amounts of LDH in your blood.

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 — Testing vitamin levels 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 — Low levels of EPO, a hormone that helps your body make red blood cells, may be a sign that other problems are responsible for anemia.

Talk to your doctor if you are experiencing any health changes. Your provider can use a range of tests to give you a diagnosis of paroxysmal nocturnal hemoglobinuria or other conditions and recommend appropriate PNH treatment options.

Find Your Team

On myPNHteam, the site for people with paroxysmal nocturnal hemoglobinuria and their loved ones, members come together to ask questions, offer advice, and share their stories with others who understand life with PNH.

Have you been diagnosed with PNH? How was your diagnosis journey? Share your experience in the comments below, or start a conversation on your Activities page.