Large Red Blood Cells (Macrocytosis)

Red blood cells are the oxygen carriers in the bloodstream. In order for it to function as normal, it needs to contain important components like hemoglobin and also be of a specific shape and size to not cause problems. In different conditions there can be a deficiency of hemoglobin or an abnormality in size and shape which can lead to various disturbances and can even culminate in serious complications.

What is macrocytosis?

Macrocytosis is a term used to describe abnormally large red blood cells (also known as erythrocytes). The development of red blood cells is a multi-stage process (referred to as erythropoiesis) that occurs within the bone marrow. The hemotopoeitic stem cells that reside in the bone marrow go through a series of developmental stages that ultimately result in the production of different types of blood cells, including erythrocytes.

Upon maturity, a red blood cell is shaped like a biconcave disc that is 6-8 micrometers in diameter and about 2 micrometers in thickness. Macrocytosis is a sign, rather than a disease by itself. The large size of red blood cells seen in macrocytosis could result from a variety of underlying conditions that can potentially affect the development of these cells. Anemia is commonly associated with this condition.

However, macrocytosis may also occur in people without anemia. Some of the causative factors could be very serious. Therefore, the presence of macrocytosis warrants further investigations into the underlying cause of enlarged red blood cells.

Types of Macrocytosis

Macrocytosis can be classified into three broad categories:

  • Megaloblastic macrocytic anemia: Megaloblastic anemia refers to a condition in which large immature red blood cells are not able to proceed further along their developmental route. The most common cause of this condition is a deficiency of folic acid and vitamin B12. Both these micronutrients are required during the last stages of the development of red blood cells. Anemia occurs when a deficiency of these macronutrients impairs DNA synthesis and prevents maturation of red blood cells. Megaloblastic macrocytic anemia may also be caused by certain drugs (antiviral and anticancer drugs) and poisons.
  • Non-megaloblastic macrocytic anemia: In non-megaloblastic macrocytic anemia, there is no impairment of DNA synthesis. However, macrocytic red blood cells and low hemoglobin levels are present. This condition is not as common as megaloblastic macrocytic anemia. The macrocytic red blood cells may be seen as a normal occurrence in newborns. Chronic alcoholism may also cause the development of this condition.
  • Macrocytosis without anemia: Macrocytosis may also occur without any accompanying signs and symptoms of anemia. Under these conditions, neither DNA syntheis nor development of red blood cells is impaired. However, the red blood cells fail to reduce their size in the terminal maturation phase. A major cause of this condition is chronic alcoholism.

Read more on iron deficiency anemia.

Signs and Symptoms

People with enlarged red blood cells are normally unaware that they have this condition. Macrocytosis is usually detected through signs and symptoms that accompany the underlying cause associated with this condition. For example, symptoms of anemia in a person may lead to investigations of blood that uncover the presence of macrocytosis as well. This condition is known as megaloblastic anemia.

Similarly, macrocytosis may get detected in individuals who get tested for other conditions. Some of the signs and symptoms that may be associated with macrocytosis include:

  • Shortness of breath due to lowered oxygen-carrying capacity of blood.
  • Fatigue and headache.
  • Paleness (also known as pallor) of skin and conjunctiva in the eye.
  • Abnormal sensations (paresthesias) such as numbness and tingling due to vitamin B12 and folate deficiency
  • Inflammation of the tongue (glossitis)
  • Depression and other mood changes
  • Diarrhea and constipation

Most of these signs and symptoms indicate the presence of anemia and nutritional deficiencies of vitamin B12 and folate.

Causes of Macrocytosis

Proper development of red blood cells could be affected by a variety of conditions. Some of the conditions associated with macrocytosis are as follows:

  • Vitamin B12 and folate deficiency: As described previously, deficiencies of vitamin B12 and folate result in macrocytosis associated with anemia.
  • Gastrectomy: Gastrectomy refers to surgical removal of either a part or whole of the stomach.
  • Malabsorption syndrome: Malabsorption syndrome can be caused by a variety of factors, such as bowel inflammation, infections, and use of certain drugs. Malabsorption syndrome results in nutrient deficiencies that can impair proper development of red blood cells.
  • Pregnancy: There is an increased demand for nutrient uptake and red blood cell formation during pregnancy. Nutritional deficiencies during pregnancy could lead to macrocytosis.
  • Alcoholism: As described previously, chronic alcoholism is a cause of both non-megaloblastic macrocytic anemia and macrocytosis without anemia.
  • Problems with DNA synthesis: Certain hereditary disorders leading to impaired DNA production can cause macrocytosis.
  • Liver disease: Non-alcoholic liver disease can also cause macrocytosis.
  • Hypothyroidism: Severe hypothyroidism is a cause of non-megaloblastic macrocytosis.
  • Bleeding: Significant and recurring loss of blood can lead to anemia and macrocytosis.
  • Drugs: Certain classes of drugs such as antiepileptics, chemotherapeutics and antivirals may cause macrocytosis.

Diagnosis of Macrocytosis

Since there are no specific symptoms of macrocytosis, a definitive diagnosis of this condition requires laboratory tests. Following are some of the laboratory tests that are useful in the detection of macrocytosis:

  • The main metric used for the diagnosis of macrocytosis is the mean cell volume or mean corpuscular volume (abbreviated as MCV). Mean corpuscular volume, which refers to the average volume of a red blood cell, is determined when a complete blood count (abbreviated as CBC) is done. The mean corpuscular volume is expressed in femtoliters (abbreviated as fL). Under normal conditions, the mean corpuscular volume of red blood cells ranges from 80-99 fL. In macrocytosis, the mean corpuscular volume of red blood cells becomes higher than 100 fL, indicating an increase in the dimensions of these cells.
  • Examination of blood smears directly under the microscope can also reveal macrocytosis of red blood cells.
  • Biopsy of bone marrow may also lead to diagnosis of macrocytosis.
  • Detection of decreases in the levels of vitamin B12 and folate in the serum may also point to macrocytosis.

Treatment of Macrocytosis

The exact treatment for macrocytosis depends on the underlying cause. However, certain supportive steps can be taken to treat the associated anemia. These supportive measures include:

  • Blood transfusion in case of severe anemia.
  • Intramuscular injections of vitamin B12.
  • Intake of folic acid supplements.

Drugs suspected to be causing macrocytosis should be stopped only under medical supervision. In case the patient is a chronic alcoholic, abstaining from alcohol consumption might help in reversing macrocytosis.

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