Anisocytosis: Types, Causes, Symptoms, Diagnosis

Anisocytosis is a medical condition where the sizes of different erythrocytes/red blood cells are unequal.

  • “Aniso” refers to unequal, and “cytosis” refers to the movement or number of cells.
  • Anisocytosis refers to excessive red blood cell size variation which can be quantitatively determined by interpreting peripheral blood films and automated assessment of red blood cell size distribution.
  • The red cell distribution width (RDW) represents a quantitative measure of anisocytosis.
  • RDW is a measure of the variability of erythrocyte volume, and it is routinely performed by automated cell counters as part of the red blood cell count.
  • It is calculated as a coefficient of variation of the distribution of RBC volumes divided by the mean corpuscular volume (MCV).
  • Anisocytosis is not a condition on its own but is associated with another condition like iron-deficiency anemia and/or other blood-related disorders.

Figure: Human red blood cells from the case of anisocytosis. Image Source: Wikipedia (Dr. Graham Beards).

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Types of Anisocytosis

Based on the size of the erythrocytes and the cause of anisocytosis, three types of anisocytosis can be observed:

a. Anisocytosis with macrocytosis

  • When the size of the erythrocytes is larger than usual, this condition is called anisocytosis with macrocytosis.
  • Anisocytosis with macrocytosis is observed in conditions like megaloblastic anemia (Vitamin B12/Folate deficiency), myelodysplasia, liver disease.
  • It is also associated with the consumption of antimetabolite or androgen drug therapy while a lesser degree of macrocytosis is seen commonly in alcoholic patients.

b. Anisocytosis with microcytosis

  • When the size of erythrocytes is smaller than usual, this condition is called anisocytosis with microcytosis.
  • Anisocytosis with microcytosis is commonly observed in iron deficiency anemia, sideroblastic anemia, certain thalassemias, lead poisoning, and certain hemoglobinopathies.

c. Anisocytosis with normocytosis

  • When the size of the erythrocytes is normal, but the number of RBCs is low, this condition is called anisocytosis with normocytosis.
  • This is commonly associated with normocytic anemia.

Causes of Anisocytosis

  • As anisocytosis is not a condition in itself, it is often associated with other forms of blood-related disorder.
  • Anemia is the primary cause of anisocytosis. There are different types of anemia that result in anisocytosis.
  • Some of the common anemia and other medical conditions associated with anisocytosis are:

a. Iron deficiency anemia

  • Iron deficiency anemia is the most common type of anemia.
  • It results due to a lack of iodine in the body usually resulting from massive blood loss or a dietary deficiency.
  • RBCs store iodine which helps in carrying and storing oxygen in the blood. When the concentration of iodine is reduced, the size of the RBCs fluctuates.
  • This anemia usually results in anisocytosis with microcytosis.
  • Anisocytosis due to iron deficiency anemia is commonly observed during pregnancy as they require more iron to produce RBCs for the baby.

b. Sickle-cell anemia

  • Sickle-cell anemia is a genetic condition that results in the formation of sickle-shaped or crescent-shaped red blood cells.
  • Because it is a genetic condition, it can be inherited.

c. Thalassemia

  • Thalassemia is another genetic disorder where the body produces abnormal amounts or types of hemoglobin.
  • As sickle-cell anemia, thalassemia can also be inherited.
  • Thalassemia also results in anisocytosis with microcytosis.

d. Hemolytic anemia

  • Hemolytic anemia is a group of disorders that results when the body starts destroying the RBCs recognizing it as a foreign body.
  • This causes a reduction in the number of red blood cells in the blood, resulting as a result of autoimmune diseases, infections or some genetic disorder.

e. Megaloblastic anemia

  • Megaloblastic anemia occurs when the number of RBC is reduced, and the size of the remaining RBCs increases than the size of a normal red blood cell.
  • A lack of Vitamin B-12 or Folate deficiency results in this type of anemia.
  • Anisocytosis with macrocytosis is observed in the case of megaloblastic anemia.

f. Aplastic anemia

  • Aplastic anemia is a bone marrow disorder that occurs when the body doesn’t produce enough blood cells.
  • This condition might be caused by viral infections, consumption of drugs associated with aplastic anemia or exposure to some toxic chemicals.

g. Pernicious anemia

  • Pernicious anemia is an autoimmune disorder that occurs when the body becomes incapable of absorbing vitamin B-12.

h. Other disorders

In addition to blood-related disorders, other medical conditions might also result in anisocytosis. Some of them are:

  1. Chronic liver disease
  2. Myelodysplastic syndrome
  3. Thyroid-related disorders
  4. Haemoglobin H disease
  5. Protein deficiency
  6. Cardiovascular-related diseases
  7. Cytotoxic chemotherapy drugs or drugs used to treat cancer

Symptoms of Anisocytosis

Since the condition is associated with the size and number of RBCs, it results in symptoms that are associated with the lack of supply of oxygen to different organs in the body. The symptoms also are similar to those of anemia and other blood-related disorders. Some of them are:

  • Weakness and fatigue
  • Shortness of breath even with minimal exertion
  • Chest pain
  • Headache and dizziness
  • Pale skin
  • Cold hands and feet

If anisocytosis is left untreated, it might lead to further complications like:

  • Reduction in the levels of white blood cells and platelets
  • Damage in the nervous system
  • A rapid increase in heart rate
  • Severe Pregnancy complications, including serious congenital disorders in the spinal cord and brain of a developing fetus (neural tube defects)

Diagnosis of Anisocytosis

The diagnosis of anisocytosis can be made through a number of ways, among which, blood smear is the most common procedure.

Blood Smear

  • A sample of blood is collected, and a thin layer of the blood is smeared on a sterile glass slide.
  • The slide is then stained, dried, and observed under a microscope of appropriate magnification.
  • The staining helps to differentiate different types as well as the size of the cells.
  • Through the smear, size, and shape, and the number of red blood cells, the amount of hemoglobin in every red blood cell, cell volume, and hemoglobin concentration in every red blood cell are observed and noted down.

Other procedures that can be used in the diagnosis of anisocytosis include:

  • Complete blood count
  • Folate test
  • Vitamin B-12 test
  • Ferritin test
  • Serum iron level


  • The treatment for anisocytosis is based on its cause.
  • Anisocytosis caused by anemia like vitamin B-12 deficiency and iron deficiency can be treated easily through the consumption of supplements and proper diet.
  • However, in the case of more severe anemia like sickle cell anemia and thalassemia, treatment is done through a blood transfusion or in some cases, a lifetime of blood transfusion.
  • In the case of megaloblastic anemia, the patient might even require a marrow transplant.


  • A proper diet with necessary nutrients and vitamins might be useful in preventing anisocytosis.
  • Besides, some changes in the lifestyle that includes proper diet, necessary supplement, and proper exercise could also be effective.


  • Simel DL, DeLong ER, Feussner JR, Weinberg JB, Crawford J. (1988). Erythrocyte Anisocytosis: Visual Inspection of Blood Films vs Automated Analysis of Red Blood Cell Distribution Width. Arch Intern Med.1988;148(4):822–824. DOI:10.1001/archinte.1988.00380040062012
  • ENGLAND, J.M., WARD, S.M. and DOWN, M.C. (1976), Microcytosis, Anisocytosis and the Red Cell Indices in Iron Deficiency. British Journal of Haematology, 34: 589-597. DOI:1111/j.1365-2141.1976.tb03605.x
  • Davor Kust, Marko Lucijanic, Kristina Urch, Ivan Samija, Ivana Celap, Ivan Kruljac, Marin Prpic, Ivica Lucijanic, Neven Matesa, Ante Bolanca (2017). Clinical and prognostic significance of anisocytosis measured as a red cell distribution width in patients with colorectal cancer, QJM: An International Journal of Medicine, Volume 110, Issue 6, June 2017, Pages 361–367,
  • Seno S (1964). Mechanisms of Induction of Anisocytosis. Acta Haemet. 31. 129-136.

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About Author

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Anupama Sapkota

Anupama Sapkota has a bachelor’s degree (B.Sc.) in Microbiology from St. Xavier's College, Kathmandu, Nepal. She is particularly interested in studies regarding antibiotic resistance with a focus on drug discovery.

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