Megaloblastic anemia

by Rosemarie Tremblay-LeMay MD FRCPC
March 3, 2022

What is megaloblastic anemia?

Megaloblastic anemia is a type of anemia caused by low levels of vitamin B12 or folate in the body. Red blood cells (RBCs) which carry oxygen in your blood require vitamin B12 and folate to develop normally. Cells use vitamin B12 and folate to produce new genetic material (DNA), which is held in a part of the cell called the nucleus.

What do red blood cells do?

Red blood cells (RBCs) are a specialized type of blood cell. RBCs are responsible for carrying oxygen from your lungs to the rest of your body and carrying carbon dioxide back to the lungs. They hold on to oxygen and carbon dioxide using a specialized protein called hemoglobin.

Red blood cells are made in a part of the bone called the bone marrow. As young RBCs mature in the bone marrow, they produce hemoglobin. Your body needs iron in order to make hemoglobin for RBCs. Once this process is complete, the RBCs are released into the bloodstream. Normal, healthy RBCs circulate in the bloodstream for about 120 days before they are removed, and their iron is recycled to make new RBCs.

Extra iron is stored in a specialized protein called ferritin. The amount of ferritin will change as the amount of iron in your body changes. For example, a person with low levels of iron in their body will have low levels of ferritin in their blood.

What is anemia?

Anemia means a decreased amount of hemoglobin in the blood. This can be due to a decrease in the number of RBCs in your blood or a decrease in the amount of hemoglobin in each RBC. Because the body uses oxygen to make energy, a person with anemia has less oxygen in their blood which can make them feel tired or short of breath.

What is vitamin B12 deficiency?

Vitamin B12 is found in food that comes from animals. The stomach produces a protein called intrinsic factor, a substance that helps the body absorb vitamin B12 in the small intestine. This process also requires substances made by the pancreas. Once absorbed, vitamin B12 is stored in the liver.

Low levels of vitamin B12 can be caused by a lack of vitamin B12 in the diet (for example, a vegan diet without supplementation), diseases involving the stomach, pancreas, or small intestine, and certain medications. Pernicious anemia is a special type of megaloblastic anemia caused by low levels of intrinsic factor, either because it cannot be produced properly or because antibodies destroy it.

What is folate deficiency?

Folate is a word that describes a group of essential vitamins. Folic acid is a form of folate found in nutritional supplements. Folates are found in fruits and vegetables and are absorbed in the small intestine. Low levels of folate can be caused by a lack of folate in the diet, diseases that prevent absorption in the small intestine, and certain medications. Women that are pregnant or breastfeeding require additional folate and it is recommended that they take supplements. Folate deficiency is rare in developed countries where folate is commonly added to flour.

How do pathologists make the diagnosis of megaloblastic anemia?

The diagnosis is usually made after blood work shows anemia with large RBCs (macrocytic) or abnormal neutrophils. Additional blood tests will reveal low levels of vitamin B12, or more rarely low levels of folate.

Low levels of vitamin B12 or folate prevent RBCs from producing a normal amount of genetic material. This causes the RBC to become abnormally large and have abnormal nuclei. Pathologists call these cells megaloblastic. Other specialized immune cells called neutrophils are often also affected.