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Megaloblastic Anemia: Causes, Symptoms, Diagnosis, Prevention, Treatments

What is Megaloblastic Anemia?

Megaloblastic anemia is a disorder of the bone marrow. A type of anemia, a blood disorder in which the number of red blood cells is lower than normal. Red blood cells transport oxygen through the body. When your body doesn’t have enough red blood cells, your tissues and organs don’t get enough oxygen.

There is a presence of erythroblasts in the bone marrow with delayed nuclear maturation because of defective DNA synthesis (megaloblasts).

Causes of Megaloblastic Anemia

There are many types of anemia with different causes and characteristics. Megaloblastic anemia is characterized by red blood cells that are larger than normal. There also aren’t enough of them. It’s known as vitamin B-12 or folate deficiency anemia, or macrocytic anemia, as well.

Megaloblastic anemia is caused when red blood cells aren’t produced properly. Because the cells are too large, they may not be able to exit the bone marrow to enter the bloodstream and deliver oxygen.

The two most common causes of megaloblastic anemia are deficiencies of vitamin B-12 or folate. These two nutrients are necessary for producing healthy red blood cells. When you don’t get enough of them, it affects the makeup of your red blood cells. This leads to cells that don’t divide and reproduce the way they should.

Vitamin B-12 Deficiency

Vitamin B-12 is a nutrient found in some foods like meat, fish, eggs, and milk. Some people can’t absorb enough vitamin B-12 from their food, leading to megaloblastic anemia. Megaloblastic anemia caused by vitamin B-12 deficiency is referred to as pernicious anemia.

Vitamin B-12 deficiency is most often caused by the lack of a protein in the stomach called “intrinsic factor.” Without intrinsic factor, vitamin B-12 can’t be absorbed, regardless of how much you eat. It’s also possible to develop pernicious anemia because there isn’t enough vitamin B-12 in your diet.

Folate Deficiency

Folate is another nutrient that’s important for the development of healthy red blood cells. Folate is found in foods like beef liver, spinach, and Brussels sprouts. Folate is often mixed up with folic acid — technically, folic acid is the artificial form of folate, found in supplements. You can also find folic acid in fortified cereals and foods.

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Your diet is an important factor in making sure you have enough folate. Folate deficiency can also be caused by chronic alcohol abuse, since alcohol interferes with the body’s ability to absorb folic acid. Pregnant women are more likely to have folate deficiency, because of the high amounts of folate needed by the developing fetus.

Differences between macrocytic anemia and microcytic anemia

Anemia is a term for low hemoglobin or red blood cells. Anemia can be divided into different types based on the volume of the red blood cells. Macrocytic anemia means that the red blood cells are larger than normal. In microcytic anemia, the cells are smaller than normal. We use this classification because it helps us to determine the cause of the anemia.

The most common causes of macrocytic anemia are vitamin B-12 and folate deficiency. Pernicious anemia is a type of macrocytic anemia due to the body not being able to absorb vitamin B-12. Elderly, vegans, and alcoholics are more susceptible to developing macrocytic anemia.

The most common cause of microcytic anemia is iron-deficiency anemia, usually due to poor dietary intake or blood loss, such as menstrual blood loss or through the gastrointestinal tract. Pregnancy, menstruating women, infants, and those with a diet low in iron may have an increased chance of developing microcytic anemia. Other causes of microcytic anemia include defects in hemoglobin production such as sickle cell disease, thalassemia, and sideroblastic anemia.

Symptoms of Megaloblastic Anemia

The most common symptom of megaloblastic anemia is fatigue. Symptoms can vary from person to person. Common symptoms include:

  • smooth or tender tongue
  • tingling in hands and feet
  • abnormal paleness of the skin
  • glossitis (swollen tongue)
  • loss of appetite/weight loss
  • diarrhea
  • nausea
  • fast heartbeat
  • numbness in extremities
  • shortness of breath
  • muscle weakness
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Diagnosing Megaloblastic Anemia

One test used to diagnose many forms of anemia is the complete blood count (CBC). This test measures the different parts of your blood. Your doctor can check the number and appearance of your red blood cells. They will appear larger and underdeveloped if you have megaloblastic anemia. Your doctor will also gather your medical history and perform a physical exam to rule out other causes of your symptoms.

Your doctor will need to do more blood tests to figure out if vitamin deficiency is causing your anemia. These tests will also help them find out whether it’s a vitamin B-12 or folate deficiency that’s causing the condition.

One test that your doctor may use to help diagnose you is the Schilling test. The Schilling test is a blood test that evaluates your ability to absorb vitamin B-12. After you take a small supplement of radioactive vitamin B-12, you’ll collect a urine sample for your doctor to analyze. You will then take the same radioactive supplement in combination with the “intrinsic factor” protein that your body needs to be able to absorb vitamin B-12. Then you’ll provide another urine sample so it can be compared to the first one.

It’s a sign that you don’t produce intrinsic factor of your own if the urine samples show that you only absorbed the B-12 after consuming it along with the intrinsic factor. This means that you’re unable to absorb vitamin B-12 naturally.

Living with Megaloblastic Anemia

In the past, megaloblastic anemia was difficult to treat. Today, people with megaloblastic anemia due to either vitamin B-12 or folate deficiency can manage their symptoms and feel better with ongoing treatment and nutrient supplements.

Vitamin B-12 deficiency can lead to other problems. These can include nerve damage, neurological problems, and digestive tract problems. These complications can be reversed if you get diagnosed and treated early. Genetic testing is available to determine if you have the MTHFR genetic mutation. People who have pernicious anemia also may be at higher risk for weakened bone strength and stomach cancer. For these reasons, it’s important to catch megaloblastic anemia early. Talk to your doctor if you see any signs of anemia so you and your doctor can come up with a treatment plan and help prevent any permanent damage.

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Treatment for Megaloblastic Anemia

How you and your doctor decide to treat megaloblastic anemia depends on what’s causing it. Your treatment plan can also depend on your age and overall health as well as your response to treatments and how severe the disease is. Treatment to manage anemia is often ongoing.

Vitamin B-12 Deficiency

In the case of megaloblastic anemia caused by vitamin B-12 deficiency, you may need monthly injections of vitamin B-12. Oral supplements may also be given. Adding more foods with vitamin B-12 to your diet can help. Foods that have vitamin B-12 in them include:

  • eggs
  • red meats (especially beef)
  • milk
  • shellfish
  • chicken
  • fortified cereals (especially bran)

Some individuals have a genetic mutation on the MTHFR (methylenetetrahydrofolate reductase) gene. This MTHFR gene is responsible for the conversion of certain B vitamins, including B-12 and folate, into their usable forms within the body. Individuals with the MTHFR mutation are recommended to take supplemental methylcobalamin. Regular intake of vitamin B-12-rich foods, vitamins, or fortification is not likely to prevent deficiency or its health consequences in those with this genetic mutation.

Folate Deficiency

Megaloblastic anemia caused by a lack of folate may be treated with oral or intravenous folic acid supplements. Dietary changes also help boost folate levels. Foods to include in your diet include:

  • peanuts
  • lentils
  • enriched grains
  • oranges
  • leafy green vegetables

As with vitamin B-12, individuals with the MTHFR mutation are encouraged to take methyl folate to prevent a folate deficiency and its risks.

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