Macrocytic anemia causes a person to have large red blood cells that cannot carry enough oxygen throughout the body. The symptoms mimic other kinds of anemia but the treatment depends on the underlying cause.

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. People may also use the term 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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Macrocytic anemia is a condition in which a person has abnormally large red blood cells and not enough healthy red blood cells.

Macrocytic anemia refers to a condition called macrocytosis in the context of anemia. Macrocytosis means that the bone marrow produces red blood cells that are too large. Healthcare professionals characterize anemia as a condition that develops when the blood does not produce enough healthy red blood cells.

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.

Types of macrocytosis

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.

The symptoms of macrocytic anemia can depend on the underlying cause. For example, those macrocytic anemia caused by a vitamin B12 deficiency may experience:

  • difficulty walking
  • uncontrollable muscle movements
  • vision problems
  • pain or tingling sensations
  • confusion
  • forgetfulness or memory loss
  • slower thinking
  • mood changes
  • unexplained weight loss
  • diarrhea
  • changes in smell or taste
  • glossitis, which refers to a painful, smooth, red tongue

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.

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.

According to a 2022 overview of research, macrocytic anemia often develops due to folate or vitamin B12 deficiency.

Vitmain B12 deficiency

These deficiencies can occur if a person cannot absorb vitamins due to an underlying condition or because their diet lacks these vitamins.

Vitamin B12 is present in animal products, such as fish, meat, dairy, eggs, and poultry. For those following a vegetarian or vegan diet, vitamin B12 is present in fortified products, such as cereals and nutritional yeast.

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

Folate deficiency, or vitamin B9 deficiency, can also cause macrocytic anemia. Pregnant and nursing individuals may 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

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.

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 fetus. However, pregnant people may develop macrocytic anemia during pregnancy as their bodies support the growth of a fetus.

During pregnancy, the body also has an 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.

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 a folic acid deficiency. 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

Macrocytic anemia can cause serious complications without treatment. These include:

  • bleeding
  • infections
  • neurological damage, such as:
    • memory loss
    • difficulty walking in a straight line (gait ataxia)
    • numbness and weakness in the hands and feet (peripheral neuropathy)

Infants born to those with a vitamin B12 deficiency may also experience developmental delays and have an increased risk of congenital defects affecting the brain and spinal cord.

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.

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.

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. However, some symptoms can take months to improve.

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.

Is macrocytic anemia serious?

Without treatment, macrocytic anemia can lead to serious complications. However, with an early diagnosis and treatment, a person’s outlook is excellent.

Macrocytic anemia, or vitamin deficiency anemia, is a condition in which a person has abnormally large red blood cells, and not enough healthy red blood cells.

It usually develops due a a deficiency in vitamin B12 or folate. However, this might happen as a result of medications or underlying conditions that cause a person to have difficulty absorbing these vitamins. Alternatively, a person may not be consuming enough vitamin B12 or folate in their diet.

Although macrocytic anemia can cause serious complications, a person’s outlook is excellent with prompt diagnosis and treatment.