Macrocytosis

What is macrocytosis?

Macrocytosis is a word that describes abnormally large red blood cells. It’s not a condition or diagnosis. Instead, you may learn that you have enlarged red blood cells when you receive results from a complete blood count (CBC). A CBC is a routine blood test providers use to monitor your health by examining your blood cells.

A CBC includes a value called mean corpuscular volume (MCV), the average size of your red blood cells. You have macrocytosis if you’re an adult with an MCV above what’s considered normal — 100 femtoliters (fL).

Macrocytosis isn’t usually a sign of something serious. Sometimes, though, enlarged red blood cells lack the essential nutrients they need to do their job — transporting oxygen throughout your body. This is what happens with macrocytic anemia. Macrocytic anemia can lead to serious health issues without treatment.

How common is macrocytosis?

Approximately 2% to 4% of people have macrocytosis. Over half of the people with macrocytosis (60%) also have anemia.

Macrocytosis without anemia is more common in infants, older adults and people who are pregnant. It doesn’t usually require treatment.

What are the symptoms of macrocytosis?

Often, the only sign of macrocytosis is a high MCV value on a CBC, which means you have enlarged red blood cells. When symptoms appear, they’re related to what’s causing your red blood cells to be large.

For example, with macrocytic anemia, you may have common anemia symptoms like weakness or pale skin. If the cause is a nutritional deficiency, you may experience symptoms like diarrhea or problems with memory or balance.

Symptoms are as varied as causes.

What causes macrocytosis?

Problems with red blood cell production in your bone marrow (where blood cells are made) and structural problems with your red blood cells can lead to macrocytosis. You may have a high MCV because you have a lot of immature red blood cells (reticulocytes) in your blood. Reticulocytes are larger than fully mature red blood cells.

Causes of macrocytosis include:

• Nutritional deficiencies: Your body needs nutrients, like vitamin B12 and folate (vitamin B9), to make healthy red blood cells. Your red blood cells may not develop normally if you’re not consuming enough of these nutrients or if a condition is preventing your body from absorbing them. Deficiencies in vitamin B12 and folate cause macrocytic anemia.
• Medications: Multiple medicines can lead to macrocytosis. The most common types include a medicine for sickle cell disease called hydroxyurea, various chemotherapy drugs for cancer treatment and antiretroviral therapy (ART) for treating HIV.
• Alcohol use disorder: Drinking too much alcohol can prevent your body from absorbing the nutrients needed to make healthy red blood cells.
• Liver disease: Macrocytosis may be a sign of liver disease. Often — but not always — liver disease is related to consuming too much alcohol.
• Hemolytic anemia: With hemolytic anemia, an underlying condition causes your red blood cells to die too soon. When this happens, your body may release reticulocytes into your bloodstream to compensate. These immature red blood cells aren’t fully formed enough to successfully transport oxygen like mature red blood cells.
• Severe blood loss: Your body may release reticulocytes into your bloodstream if you lose large volumes of blood. As with hemolytic anemia, your body may release immature blood cells early to compensate for the lost blood cells.
• Myelodysplastic syndrome: This type of cancer prevents your bone marrow from producing healthy red blood cells.
• Hypothyroidism: People with this condition may have macrocytosis, with or without anemia.

Sometimes, macrocytosis doesn’t have a clear cause. This is especially the case if you have macrocytosis but don’t have anemia.

How is macrocytosis diagnosed?

Macrocytosis is a description of enlarged red blood cells, not an official diagnosis. Your red blood cells are larger than normal if the MCV result on a CBC is greater than 100 fL.

Sometimes, healthcare providers can determine likely causes based on how severe your macrocytosis is. For example, an extremely high MCV (from 110 to 115 fL) often signals a severe form of macrocytic anemia called megaloblastic anemia.

What tests will be done to determine what’s causing macrocytosis?

If your healthcare provider is concerned about your enlarged red blood cells, they may ask questions to determine the cause. They may ask about your medical history, including what prescription drugs you’re taking, your diet and alcohol consumption. They may perform additional tests, including:

• Peripheral blood smear: A healthcare provider will view your blood cells under a microscope. They’ll look for abnormalities related to issues that can lead to macrocytosis, like problems with blood cell development.
• Vitamin B12 and folate levels: Low levels of vitamin B12 or folate may signal that a nutritional deficiency is depriving your red blood cells of the ingredients needed to develop normally.
• Reticulocyte count: This test helps your provider determine if your high MCV is related to having many immature red blood cells in a blood sample.
• Liver function test: This test can help your provider determine how well your liver absorbs the nutrients needed to make healthy red blood cells.
• Bone marrow biopsy: Your provider may perform this procedure if they suspect you have a condition that’s interfering with red blood cell production in your bone marrow. They’ll remove a sample of your bone marrow and view the cells under a microscope to check for abnormalities.

How is macrocytosis treated?

You may not need treatment, especially if you don’t have anemia symptoms and your test results don’t show any abnormalities. Otherwise, treatment depends on what’s causing your large red blood cells.

If your macrocytosis is related to a nutritional deficiency, you may need to change your diet or take supplements. If the issue is related to a medication, your healthcare provider may adjust the dosage or prescribe a different type of medicine. You may need a blood transfusion if you have severe anemia along with macrocytosis.

Follow your healthcare provider’s treatment plan based on what’s causing your macrocytosis.

Can you cure macrocytosis?

Often, addressing the underlying cause reverses macrocytosis. Ask your healthcare provider about how treatments will likely impact your health.

How can I reduce my risk of having macrocytosis?

You may not be able to prevent all potential causes of macrocytosis, but healthy habits can reduce your risk. For example, eating foods rich in vitamin B12 and folate — like fish, dairy and fortified cereals — can reduce your risk of macrocytic anemia. You can reduce your risk of macrocytosis by limiting your alcohol consumption.

Also, don’t skip annual blood tests. Macrocytosis is usually an incidental finding on routine blood work. Early diagnosis and treatment can often stop a condition from progressing into something serious.

What happens if macrocytosis is left untreated?

Only a healthcare provider can determine whether your macrocytosis is cause for concern. If you have macrocytosis and anemia, it’s essential to get treated. Untreated macrocytic anemia can cause serious medical problems.

What questions should I ask my doctor?

Follow your healthcare provider’s guidance about what steps to take if you learn that you have abnormally large red blood cells. Questions include:

• Should I be concerned about my high MCV?
• What tests will I need to determine what’s causing macrocytosis?
• Will I need treatments to address what’s causing my enlarged red blood cells?
• Are there lifestyle changes I can make to reverse my macrocytosis?

A note from Cleveland Clinic

Remember that macrocytosis or a high MCV value isn’t always cause for concern, so don’t be alarmed if these numbers are high on a CBC. Follow your healthcare provider’s guidance on how to interpret your results. Depending on your results, your provider may recommend dietary changes or suggest supplements. Don’t be afraid to ask how treatments will impact your blood cells and your overall health.