Macrocytosis: What You Need to Know

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Macrocytosis is a condition in which the red blood cells (RBCs) are larger than normal but not functioning as they should. It can cause fatigue, and sometimes there are other symptoms related to underlying causes of macrocytosis.

This condition usually is caused by low vitamin B12 or folate levels, and it also can occur with other conditions, including liver disease and cancer, or from taking certain medications. The diagnosis involves a standard complete blood count (CBC) test that measures the RBC count and size. Sometimes red blood cells also will be examined under a microscope.

Usually, the diagnostic process includes tests to identify the cause of macrocytosis. Medical management, such as vitamin B12 or folate supplementation, is usually effective, but treatment may need to be repeated to prevent recurrence of macrocytosis. 

Large red blood cells can be examined with a microscope

Ed Reschke / Getty Images

Symptoms 

Generally, macrocytosis (also known as megalocytosis or macrocythemia) is associated with anemia (macrocytic anemia), which is diminished RBC count. The condition causes a decrease in oxygen delivered to the body’s tissues. Usually, the symptoms are mild to moderate, but sometimes the effects can be severe.

Common symptoms of macrocytosis include: 

  • Fatigue 
  • Headaches 
  • Difficulty concentrating 
  • Lightheadedness or dizziness 
  • Pale skin 

These symptoms can wax and wane in severity, and they may linger for months or longer before you feel the need to see a doctor.

For example, you might feel energetic when you wake up from sleeping but then become more tired than usual as the day goes on. Or you may have some days of feeling more worn out than others. And illnesses, such as the common cold, can make you especially tired when you have macrocytosis. 

Associated Symptoms 

Often macrocytosis is accompanied by other symptoms related to its cause. 

Associated symptoms you may experience with macrocytosis include: 

  • Diarrhea, which can be a sign of malabsorption, can make you deficient in vitamin B12 and other nutrients. 
  • Enlarged tongue (glossitis) can develop due to vitamin B12 deficiency.
  • Peripheral neuropathy causes numbness of the fingers and toes and can result from a vitamin B12 deficiency or alcoholism.
  • Weakness can develop from an iron deficiency.
  • Bruising or bleeding can occur due to leukemia, cancer of the blood and bone marrow.
  • Enlarged abdomen due to splenomegaly (enlarged spleen) can occur with RBC breakdown. 
  • Jaundice (yellow skin and whites of the eyes) can result from liver failure. 

If you have these symptoms along with fatigue or other direct signs of macrocytosis, let your doctor know in order to provide the proper diagnostic testing. 

Causes 

There are several causes of macrocytosis. The most common cause is a deficiency in vitamin B12 and folate (vitamin B9). These two vitamins cannot be produced in the body and must come from your diet.

There are several potential causes of vitamin B12 deficiency, including: 

  • Insufficient amounts in your diet (dietary sources include liver, beef, chicken, fish, dairy products, eggs, food fortified with vitamin B12)
  • Malabsorption from the intestine, such as from infection, celiac disease (an immune reaction from eating gluten, a protein in wheat, barley and rye), or inflammation 
  • Pernicious anemia, an uncommon condition in which the absorption of vitamin B12 is impaired due to a lack of intrinsic factor, a protein that is needed to absorb this vitamin

Potential causes of folate deficiency include:

  • Insufficient folic acid in the diet (sources include leafy green vegetables, fruit, meat, and fortified cereals)
  • Drinking too much alcohol
  • Conditions affecting the lower digestive tract
  • Cancer
  • Some medications
  • Pregnancy

Other causes of macrocytosis include:

  • Alcoholism 
  • Liver disease
  • Hypothyroidism (underactive thyroid)
  • Leukemia 
  • Bone marrow disease 
  • Myelodysplastic syndrome (MDS), a condition in which the blood cells do not develop normally
  • Some medications, including those used in chemotherapy 
  • Hemolysis (breakdown of RBCs), resulting in rapid production of RBCs
  • Lesch-Nyhan syndrome, an inherited metabolic disorder characterized by overproduction of uric acid

Pathophysiology 

The red blood cells in the body can be large for several reasons. Without vitamin B12 and folate, RBCs remain in an immature stage of development, which is larger than their mature size. 

With some metabolic problems, such as those caused by alcoholism or liver disease, fat can accumulate in the RBCs, causing them to be enlarged. Problems with the bone marrow or that result from chemotherapy can prevent the RBCs from maturing properly as they form. 

Diagnosis 

Macrocytosis is generally detected with a complete blood count test, which may be ordered to evaluate symptoms or as a routine screening. If you are found to have enlarged RBCs, you may also need to have diagnostic tests to determine the cause.

Generally, macrocytosis results from anemia, but macrocytosis without anemia also can occur and may need the same diagnostic tests to determine the cause.

Blood measurements that can identify macrocytosis include the following, which are commonly reported as part of the CBC:

  • Mean corpuscular volume (MCV), which measures the average size of the RBCs, is usually greater than 100 femtoliter (fL) in macrocytosis.
  • Red cell distribution width (RDW) measures the variation in size of the RBCs. A normal range for RDW is 11.8%–14.6%, and it is expected to be high in macrocytosis due to the variation in RBC size.

Depending on your other symptoms or medical conditions, your doctor may order additional tests to identify the cause of your macrocytosis. These include looking at the white blood cell count, which is commonly part of the CBC.

Tests you might have:

Treatment 

The treatment of macrocytosis centers on correcting the cause, when possible. Oftentimes, vitamin B12 and/or folate supplementation will correct the problem. If you cannot absorb vitamin B12 adequately due to gastrointestinal issues, you may need to get B12 injections rather than taking a supplement by mouth. 

Your doctor may prescribe another treatment if there is a different cause of your macrocytosis. 

Prevention 

Preventing macrocytosis generally involves making sure you get adequate nutrients in your diet. Having regular medical checkups is important as well. Your doctor may detect early signs of the condition and initiate treatment before it begins to affect your quality of life. 

If you have a medical condition that could predispose you to macrocytosis, it’s especially important that you have regular medical evaluations so that problems such as macrocytosis can be identified and treated at early stages.

Summary

Macrocytosis means that your red blood cells are larger than normal. It is associated with anemia, when you also have insufficient numbers of properly functioning red blood cells.

Macrocytosis is usually caused by low vitamin B12 or folate levels, but there are other reasons it develops, including from liver disease, alcoholism, and from taking certain medications. Treatment will depend on the underlying cause. Treatment may require taking in additional vitamin B12 and folate.

A Word From Verywell

Macrocytosis can develop from several different health issues. Sometimes inadequate dietary intake of vitamin B12 and/or folate can be the cause, but your doctor may look for other causes too, especially if you have symptoms of other medical conditions.

If you have been feeling tired, dizzy, or just not like your usual self, make sure you see your doctor to assess your condition and get the right treatment.

Frequently Asked Questions

What is macrocytic anemia?

Macrocytic anemia is a condition in which the red blood cells (RBCs) are enlarged and often low in number. 

How serious is macrocytosis?

Macrocytosis is usually mild to moderate but can become severe. It can be due to a manageable cause (such as a vegan diet, which can be treated with supplements) or be due to a serious illness, such as liver disease or cancer. 

Is macrocytosis reversible?

Sometimes. Macrocytosis is often reversible with treatment. Usually taking vitamin B12 or folate supplements or eating foods containing these nutrients can reverse the condition. If it is caused by an underlying condition, such as leukemia, treatment of that illness may resolve macrocytosis, a much less concerning condition.

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