Macrocytosis (Enlarged Red Blood Cells)

What is macrocytosis?

Macrocytosis is the term for enlarged red blood cells. These blood cells, also known as erythrocytes, may be larger than normal for various reasons that affect its development. Therefore further investigations are necessary to identify the cause, as some of these causative factors can be very serious in nature. Macrocytosis is not a specific disease but rather a term to described abnormally enlarged red blood cells. It is often associated with anemia, where there is a lower than normal amount of hemoglobin in the blood. However, enlarged red blood cells may occur on its own without anemia.

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Macrocystosis and MCV

Macroytosis is often reported in terms of mean cell volume (MCV) also known as mean corpuscular volume. It is a test that is done as part of a complete blood count (CBC). Blood is placed in a centrifuge which is device that spins it around at high speed. The red blood cells become packed together and this is known as hematocrit. The hematocrit is then divided by the total number of red blood cells and then multiplied by 10.

The result is an indication of the size of the red blood cells or the number of red blood cells. It is expressed as femtoliters or fL.The normal range is between 80 to 99fL and the value is greater than 100fL in macrocytosis. In a person with anemia, where the hemoglobin is low yet the MCV is high, it can be determined that the red blood cells are larger than normal. This is known as macrocytic anemia.

Macrocystosis Reasons

Red blood cells form in the bone marrow. Special immature blood cells known as hematopoietic stem cells in the bone marrow undergo different stages of development until the fully formed mature red blood cell is released into the bloodstream. The size and shape of red blood cells are normally constant. A mature red blood cell is disc-shaped with a depressed central portion – biconcave disc. It is about 6 to 8 micrometers in diameter and about 2 micrometers thick on average.

Macrocytosis Anemia

Megaloblastic Macrocytic Anemia

In the last stages of red blood cell development, folic acid and vitamin B12 are required. When these nutrients are deficient, DNA synthesis is impaired and the red blood cell cannot mature fully. This type of anemia is seen with vitamin B12 and folic acid deficiency. Less commonly, certain poisons, antiviral drugs and cancer drugs (chemotherapy) may also cause megaloblastic anemia.

Picture from Wikimedia Commons

Nonmegaloblastic Macrocytic Anemia

In these types of macrocytic anemias, DNA synthesis is not affected. This is a less common form of macrocytic anemia. Megaloblastosis is not present although the red blood cell is larger than normal (macrocyte) and hemoglobin levels are low. These types of red blood cells may be seen normally in newborns. It mainly arises in life with chronic alcoholism.

Macrocytosis without Anemia

This is similar to non-megaloblastic macrocytic anemia except that the anemia component is not present. In other words there is no deficiency of hemoglobin. DNA synthesis is unaffected and red blood cell development is normal but the cell fails to “shrink” in the latter stages of maturation. Chronic alcoholism is a major cause here as well.

Macrocytosis Causes

  • Dietary deficiency of vitamin B12 and folic acid.
  • Surgical removal of part of the stomach or the entire stomach – gastrectomy.
  • Malabsorption syndrome due to inflammation of the bowels, infections, drugs or other causes.
  • Alcoholism – long term alcohol misuse.
  • Pregnancy – increased demands.
  • Hereditary disorders of DNA production.
  • Liver disease
  • Hypothyroidism
  • After significant blood loss, especially if bleeding occurs again.
  • Drugs such as antiviral medication, chemotherapy and some antiepileptics.

Macrocytosis Symptoms

Most people with macrocytosis never know they have the abnormality unless it is associated with megaloblastic anemia. In these cases it is the symptoms of megaloblastic anemia and the symptoms of the causative diseases that may highlight a problem.

Anemia symptoms

These symptoms are largely related to the low oxygen-carrying capacity of the blood. It becomes more obvious when there is a greater oxygen demand, like during physical activity, but the blood cells cannot compensate.

  • Shortness of breath
  • Headaches
  • Fatigue
  • Pallor – paleness of the skin and eyes (conjunctival pallor).

These symptoms could also be due to the underlying causative diseases.

Vitamin B12 and folate deficiency symptoms

Deficiency of essential nutrients like vitamin B12 and folate (vitamin B9) causes a host of symptoms sometimes evident even before the anemia symptoms are noticed.

  • Paresthesias – abnormal sensations such as tingling and numbness.
  • Glossitis – inflamed tongue.
  • Mood changes and even depression.
  • Indigestion, diarrhea or constipation.

Macrocytosis Diagnosis

The symptoms of macrocytosis, particularly macrocytic anemia and nutrient deficiency, may be seen with a number of other diseases. Therefore the first conclusive indication of the possibility of macrocytosis is upon blood tests like a complete blood count (CBC). The mean cell volume (MCV) is higher than normal. Other tests that may be conducted includes :

  • Peripheral blood smear where the blood cells are examined under a microscope.
  • Serum vitamin B12 and folate to measure the nutrient levels in the blood.
  • Bone marrow biopsy and aspiration.

Macrocytosis Treatment

The treatment should be directed at the cause of the macrocytosis once it is diagnosed. In the meantime, the following supportive measures may be commenced :

  • Transfusion with packed red blood cells if severely anemia.
  • Vitamin B12 injections in the muscle (intramuscularly).
  • Folate supplements.

Dietary changes may be implemented to ensure that a person is consuming foods rich in vitamin B12 and folate if necessary. Drugs that may be causing macrocytosis should not be stopped immediately without first seeking medical advice. Alcoholics with macrocytosis may find that abstaining from alcohol will reverse the changes in the red blood cells. Substance abuse rehabilitation and ongoing recovery support is often necessary.

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