Macrocytic anemia causes unusually large red blood cells that are not able to carry oxygen throughout the body efficiently. It is a medical condition that may occur with various diseases and causes nutritional problems. Like in other types of anemia, the red blood cells do not carry enough oxygen.

Hemoglobin is an iron-containing protein in red blood cells that transports oxygen around the body. Deficiencies in vitamin B12 or folate often cause macrocytic anemia, also sometimes called vitamin deficiency anemia.

This article looks at the causes and symptoms of macrocytic anemia, the treatment options, and how to prevent complications.

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Macrocytosis is a term that describes a condition in which a person’s blood cells are too large. It often occurs along with anemia, a condition in which there are either not enough healthy red blood cells to carry oxygen to all the tissues or the existing cells are not as efficient.

Doctors use a unit called femtoliters to measure the size of blood cells. Usually, red blood cells are between 80–100 femtoliters (fL). Doctors consider red blood cells larger than 100 fL as macrocytic.

When the cells grow too large, there are fewer of them, and they contain less hemoglobin. This means the blood is not as oxygen-rich as it should be. Low blood oxygen can cause a range of symptoms and health problems.

Doctors classify macrocytosis into two broad categories:

  • Megaloblastic macrocytosis: This is the most common form. It occurs when a person cannot produce DNA because of a B12 or folate deficiency.
  • Nonmegaloblastic macrocytosis: This can happen when there is a liver, spleen, or bone marrow problem.

Both of these types can occur along with anemia. One of the most common is megaloblastic.

Anemia develops gradually, so a person may not notice any symptoms until it is severe. When symptoms appear, they may include:

Macrocytic anemia is only one type of anemia. All anemia types have similar symptoms, so a doctor uses blood tests to diagnose a person’s specific anemia. However, different types of anemia also have unique symptoms, so sometimes a doctor may be able to identify the type based on symptoms alone.

When people develop macrocytic anemia due to a B12 deficiency, they may have other symptoms. These include:

  • weakness, pain, numbness, or tingling in the hands or feet
  • instability when walking
  • memory loss

These symptoms may resolve after treatment but can become permanent if left untreated.

Doctors use a person’s symptoms, medical history, and blood tests to diagnose macrocytic anemia.

Tests that can help diagnose macrocytic anemia include:

  • Hemoglobin: A standard complete blood count (CBC) measures hemoglobin. If it is below 12 grams per deciliter (g/dL) it can indicate anemia.
  • Red blood cell indices: These measurements are part of the CBC. A mean corpuscular volume higher than 100 fL means that the red blood cells are large and macrocytic.
  • Blood smear: This involves looking at the blood cells under a microscope to see if they are macrocytic or megaloblastic. It also shows if cells are cancerous.
  • Reticulocyte count: This is the number of immature red blood cells.

Folate or vitamin B12 deficiency typically causes macrocytic anemia. If a person cannot absorb vitamins due to an underlying condition or because their diet lacks these vitamins, they may have a deficiency.

Animal products are rich in B12, so people eating a vegan or vegetarian diet have an increased risk of a B12 deficiency.

In other cases, people may eat enough foods with B12 but are unable to absorb the vitamin due to autoimmune disorders, cancer, alcohol addiction, or inflammatory bowel disease.

Folate deficiency, sometimes known as vitamin B9 deficiency, can also cause macrocytic anemia. Pregnant and breastfeeding or chestfeeding people use more folate and are more likely to develop a deficiency.

People who do not eat enough folate-rich foods can also become deficient. Diseases that interfere with the body’s ability to absorb nutrition, such as celiac disease, can lead to folate deficiency.

Other causes of macrocytic anemia may include:

  • medications, including HIV drugs, cancer drugs, and others that suppress the immune system
  • liver disease
  • hypothyroidism
  • rare metabolic disorders

Each of these factors can make it more difficult for the body to absorb and metabolize essential nutrients.

In very rare cases, a bone marrow disorder that prevents the body from producing enough healthy blood cells can cause macrocytic anemia.

Pregnant people must have healthy blood flow as the body’s demand for red blood cells increases during pregnancy to provide enough oxygen to both itself and the baby. However, pregnant people may develop macrocytic anemia during pregnancy as their bodies support the growth of a fetus.

During pregnancy, the body also has increased demand for folic acid and vitamin B12. Often, a person has problems getting enough nutrients from their diet alone, leading to deficiencies in certain vitamins and minerals, including folic acid and B12, leading to macrocytic anemia.

Also, viral infection and certain health conditions during pregnancy can cause macrocytic anemia. These include rubella (German measles) and certain types of hepatitis.

When a person shows signs of macrocytic anemia, a doctor orders several blood tests to find the underlying cause. They may also ask questions about a person’s diet, lifestyle, and other symptoms.

In most cases, oral folic acid taken at 1–5 milligrams (mg) daily resolves the issue. Alternatively, a doctor may recommend vitamin injections. Injecting vitamins ensures the body can absorb them even if an underlying condition, such as celiac disease, prevents vitamin absorption.

Eating more foods containing vitamin B12 may improve symptoms if a person is deficient in this vitamin because of their diet.

Other treatment options include:

  • changing medications when a drug interferes with vitamin absorption
  • taking medication for certain autoimmune or liver diseases
  • taking medication for thyroid disorders
  • making lifestyle changes, such as avoiding alcohol
  • having blood transfusions or bone marrow transplants for bone marrow disorders

When the blood does not have enough hemoglobin, it cannot carry enough oxygen. The body may increase heart rate or blood pressure to try to fix this. Left untreated, anemia can cause heart failure, an enlarged heart, and circulatory problems.

When macrocytic anemia develops due to a problem with the bone marrow or an organ, this underlying cause can trigger further complications.

Vitamin deficiencies cause most cases of macrocytic anemia, which leads to various complications depending on the vitamin:

Vitamin B12 deficiencies

Vitamin B12 deficiency can cause:

  • neural tube defects in babies born to people with a B12 deficiency
  • infertility
  • stomach cancer
  • mobility problems and tingling in the hands and feet
  • memory loss

Folate deficiency

Folate deficiency can cause:

  • neural tube abnormalities in babies born to people with a folate deficiency
  • infertility
  • an increased risk of some cancers, including colon cancer
  • cardiovascular health problems
  • an increased risk of premature labor in pregnant people
  • an increased risk of a placenta rupture before or during childbirth

The following are answers to additional questions about macrocytic anemia.

How long does it take to correct macrocytic anemia?

Once a person receives a diagnosis and begins treatment with B12 or folate supplements, they should see their blood hemoglobin values gradually return to normal. This may take just a few weeks to see improvement in symptoms but could take several months.

Why does the liver cause macrocytic anemia?

Macrocytic anemia can occur with liver diseases such as hepatitis. A high cholesterol deposition into the membranes that enclose red blood cells may be the cause.

Does leukemia cause macrocytic anemia?

In rare cases, leukemia may cause macrocytic anemia. A vitamin deficiency is the more likely cause. A person’s doctor can do a thorough evaluation to determine the cause and the appropriate treatment.

A doctor can manage most cases of macrocytic anemia with vitamins. They will continue to monitor a person’s B12 or folate levels and use blood tests to determine whether red blood cells have returned to their typical size.

While most people recover with prompt treatment, they may need periodic checks for anemia.

When an underlying disease causes macrocytic anemia, a person’s outlook depends on what disease causes the deficiency and its treatment.

Macrocytic anemia often goes undiagnosed until it becomes severe because it can time to develop symptoms. People with anemia symptoms, a family history of anemia, or those who have or are at risk of developing a condition linked to macrocytic anemia should see a doctor to get a blood test for evaluation.