Types of Macrocytic Anemia

Types of Macrocytic Anemia

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Regardless of its cause, anemia can make you feel tired.

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Anemia describes a variety of blood disorders, all of which are characterized by a deficiency of hemoglobin in your bloodstream. Because hemoglobin is the oxygen-carrying molecule in your blood cells, a drop in hemoglobin concentration may interfere with your red blood cells' capacity to deliver oxygen to your tissues. Over the years, doctors have learned that some types of anemia are consistently associated with red blood cells that are larger than normal. These conditions are collectively called macrocytic anemias and their treatment typically depends on their underlying cause.

Normal Large Red Blood Cells

Red blood cells originate in your bone marrow, where any number of factors or conditions can interfere with their production and alter their size, shape or hemoglobin content. When macrocytes -- large red blood cells -- are discovered in your circulation, your doctor must first decide if they are associated with an underlying medical problem.

Babies, children and pregnant women often have enlarged red cells but have no condition that might cause it, and many healthy people inherit the tendency to make macrocytes. If your macrocytes are associated with anemia, your doctor may order further tests.

Bone Marrow Changes

Once macrocytic anemia has been diagnosed, the next step is to determine whether it is megaloblastic or nonmegaloblastic. Megaloblasts are abnormally large, immature red blood cells in your bone marrow, and their presence can only be detected with a bone marrow biopsy. But the process that produces megaloblasts -- interrupted red cell maturation due to impaired production of DNA -- also affects other cells, such as white blood cells.

So, finding specific types of abnormal white blood cells in your circulating blood reliably predicts whether you have megaloblastic or nonmegaloblastic anemia. This distinction offers a hint about the underlying cause of your macrocytic anemia.

Broad Categories

A September 2006 review in “Clinical Medicine and Research” categorized macrocytic anemias into those caused by drugs and toxins, nutritional deficiencies, bone marrow disorders or other chronic diseases. Alcoholism is the most common cause of nonmegaloblastic macrocytic anemia.

Many medications, such as methotrexate (Rheumatrex), phenytoin (Dilantin) and several anti-HIV drugs, cause megaloblastic macrocytic anemia. The most common nutritional causes of macrocytic anemia are vitamin B12 and folate deficiencies, both of which cause megaloblastic anemia.

Primary bone marrow disorders, such as leukemia or myelodysplasia, typically cause megaloblastic macrocytic anemia. Liver disease and hypothyroidism are chronic disease states that cause a macrocytic anemia which is nonmegaloblastic.


The divisions between nonmegaloblastic and megaloblastic anemias, as well as the distinctions among macrocytic, normocytic and microcytic anemias -- large, normal and small red blood cells, respectively -- are somewhat artificial, as the same disease could provide different pictures at various points in time.

For example, while alcoholism alone may cause nonmegaloblastic macrocytic anemia, people who abuse alcohol are often folate-deficient, as well, which could trigger a megaloblastic macrocytic anemia. Similarly, a primary bone marrow disease, like leukemia, may initially be associated with macrocytic anemia. As your bone marrow is progressively replaced by leukemia cells, your remaining red blood cells might have a variety of shapes and sizes, including many that are too small. So, while macrocytosis offers some direction in diagnosing the cause of anemia, it is only one clue.