Diagnosing and Monitoring PNH: Why How You Feel Matters as Much as Your Labs

If you have paroxysmal nocturnal hemoglobinuria (PNH), you probably get a lot of blood tests. These tests show your care team what is going on inside your body. But numbers don't tell the whole story. How you feel matters, too.

Flow cytometry: The test that confirms PNH

Flow cytometry is the main test doctors use to confirm PNH. It looks at the outside of your blood cells. PNH cells are missing proteins that normally protect them. A high-sensitivity version of this test can find very small numbers of PNH cells, as few as 1 in every 10,000 cells.^1-3

The lab usually checks both red and white blood cells. It also looks for more than one marker. Testing this way helps give a more accurate result.^3,4

What your PNH clone size means

PNH starts with a change in a gene called PIGA. You are not born with this change. It happens during your lifetime in a stem cell in your bone marrow. That cell then makes copies of itself. Doctors call this group of cells a "clone."¹

Your clone size is the percentage of your blood cells that are missing some or all of their protective proteins. For example, a clone size of 30 percent means about 30 out of every 100 cells are PNH cells.⁴

Your report may also sort your red blood cells into types:²

• Type I cells are normal.
• Type II cells are missing some of their protective proteins.
• Type III cells are missing all of them. These cells break apart the most easily.

Clone size is very different from person to person. PNH is also closely linked to bone marrow problems. Your risk of PNH is higher if you have aplastic anemia, a condition where the bone marrow can't make enough healthy blood cells. In one large study, about half of all people with PNH had a history of aplastic anemia or a similar condition.^1,5

Clone size matters. People with larger clones tend to have more disease activity and more blood clots. But people with small clones can have serious problems, too. That is why your doctor keeps checking. If your PNH is stable, repeating flow cytometry once a year may be enough. You may be tested more often if your clone size or symptoms change.^4,5

Key lab tests to know

Other blood tests show how much hemolysis is happening. Hemolysis means red blood cells are breaking apart. Common tests include:^1,2,6

• LDH (lactate dehydrogenase) – This is an enzyme found in red blood cells. A high LDH can be a sign that red blood cells are being destroyed.
• Hemoglobin – This protein in red blood cells carries oxygen around your body. A low level means you have anemia.
• Reticulocyte count – Reticulocytes are young red blood cells. A high count can mean your body is making new cells to replace ones that were destroyed. A low count can mean your bone marrow is not making enough red blood cells.
• Haptoglobin and bilirubin – Low haptoglobin and high bilirubin are also signs that red blood cells are breaking down.

Some people on treatment have a second kind of hemolysis. In this type, red blood cells are removed in the spleen and liver. Doctors call this extravascular hemolysis. With this type, your LDH may come down, but your hemoglobin can stay low.^7,8

Why lab numbers are not the whole story

Labs are important tools, but they can't measure everything you feel. Fatigue does not always line up with your lab results. In one large study, fatigue was common whether people's clones were big or small.^5,7

One US survey asked 122 people being treated for PNH about their health. Most still had fatigue. More than 1 in 3 had shortness of breath, headaches, back pain, trouble focusing (sometimes called "brain fog"), or trouble sleeping. Nearly 9 in 10 said their health got in the way of their daily activities.⁷

Your symptoms are real and important information. If you feel worse, tell your care team, even if your labs look stable.

How to track your symptoms

A symptom log can help you and your doctor spot patterns. Symptoms can sometimes start or get worse after something stresses your body, like an infection. Surgery and pregnancy can also bring extra risks with PNH, so it’s helpful to keep a record of these things, too. Other things to track include:¹

• Energy – Rate your energy each day from 1 to 10.
• Urine color – Write down any dark urine and the time of day.
• Pain and breathing – Note any pain or shortness of breath.
• Focus and sleep – Note days when your thinking feels slow or you sleep poorly.
• Daily life – Note missed work, extra naps, or canceled plans.
• Lab dates – Add each blood test date to your log. This helps you spot times when your labs and your symptoms don't match.

Getting ready for your hematology visit

Before each visit, look back over your log. Questions you might ask include:¹

• How has my clone size changed since my last test?
• What do my latest LDH, hemoglobin, and reticulocyte results mean?
• Could my symptoms mean my hemolysis is not fully under control?
• How often should I have blood tests?
• Which vaccines do I need, and am I up to date?

Speaking up helps your care team spot disease that is not well-controlled. Let your doctor know if your symptoms are affecting your quality of life. They may be able to suggest treatments that can help.¹

Talk to your doctor

You know your body best. Your labs and your daily life both matter. Share both with your hematologist during each visit. You are not alone in managing PNH.