What Is It, Causes, Diagnosis, and More

Author: Nikol Natalia Armata

Editors: Ahaana Singh, Ian Mannarino, MD, MBA

Illustrator: Jillian Dunbar

Copyeditor: Joy Mapes

What is anisopoikilocytosis?

Anisopoikilocytosis refers to a condition characterized by blood with varying shapes and sizes of red blood cells (RBCs). Usually, RBCs, also called erythrocytes, are nearly identical in shape and size. RBCs are typically a circular shape with a diameter of approximately 7.5 micrometers and lighter coloring in the center, referred to as central pallor. 

The term anisopoikilocytosis comes from the Greek words “aniso-”, which means uneven, and “poikilo-”, which means of a great variety. Accordingly, anisopoikilocytosis encompasses two different conditions: anisocytosis, or RBCs with uneven sizes; and poikilocytosis, or RBCs of variant shapes. By definition, anisopoikilocytosis is characterized by the presence of both anisocytosis and poikilocytosis. 

What causes anisopoikilocytosis?

The most common causes of anisopoikilocytosis are blood disorders, like thalassemia and types of anemia, as well as other chronic disorders and nutritional deficiencies. Thalassemia is an inherited condition, in which production of hemoglobin, the protein in RBCs responsible for carrying oxygen to tissues, is impaired or reduced. Thalassemia generally results in severe anisopoikilocytosis, with RBCs that resemble teardrops (i.e., dacrocytes) and have a concentration of hemoglobin in their center and periphery (i.e., target cells, also known as codocytes).

Types of anemia that can cause anisopoikilocytosis include iron deficiency, hemolytic, megaloblastic, and sickle cell anemias. Iron deficiency anemia, caused by a lack of iron, is characterized by the presence of RBCs that may be elongated and oval shaped (i.e., elliptocytes), as well as dacrocytes and target cells. Meanwhile, hemolytic anemia features small RBCs that lack the central pallor (i.e., spherocytes) and fragments of RBCs with irregular shapes and sizes (i.e., schistocytes). Megaloblastic anemia can morphologically change the RBCs into elliptocytes and dacrocytes. Lastly, sickle cell anemia is an inherited condition affecting the formation of hemoglobin. This causes most of the RBCs to lose their flexibility and take the shape of a first-quarter, sickle moon.

Aside from anemias, several chronic disorders can result in anisopoikilocytosis. For example,  cardiac valvular diseases damage heart valves, which may then produce irregular flows of circulating blood. These irregular flows can consequently affect the shape and size of RBCs. Anisopoikilocytosis can also be a complication of chronic liver or kidney disease.

Additionally, nutritional deficiencies that are associated with malnutrition, like folate and B12 deficiencies, may lead to anisopoikilocytosis. Chronic alcoholism can also affect the formation of blood cells and result in anisopoikilocytosis. 

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What are the signs and symptoms of anisopoikilocytosis?

The signs and symptoms of anisopoikilocytosis vary depending on the underlying cause. In cases of anemia, the most common symptoms are weakness, shortness of breath, dizziness, and headaches. Additional signs that may present with anemia include an increased heart rate (i.e., tachycardia), low blood pressure (i.e., hypotension), as well as cold and pale-colored skin. Individuals with thalassemia may experience similar signs and symptoms as those with anemia while also having facial bone deformities, delayed development, and dark urine.  Lastly, nutrient deficiency usually causes angular cheilitis, or the presence of red, swollen patches in one or both corners of the mouth. 

How is anisopoikilocytosis diagnosed and treated?

Most often, anisopoikilocytosis is diagnosed by a peripheral blood smear. A peripheral blood smear involves viewing a blood sample under a microscope to examine the morphology (e.g., size, shape, other characteristics) of the blood cells. A blood test called a complete blood count (CBC) can be an additional source of information, particularly when anemia is suspected. A CBC measures the number of red blood cells, white blood cells, and platelets in an individual’s blood. A CBC can also provide more detailed information, like the amount of hemoglobin in the blood or the Mean Corpuscular Volume (MCV), a measurement of the average size of the RBCs. Other blood tests (e.g., serum iron tests, vitamin B12 and folate tests, hemoglobin electrophoresis) may also be useful. Detailed medical history and genetic testing may be taken into consideration when inherited conditions, like thalassemia, are suspected.

Treatment for anisopoikilocytosis varies depending on the underlying cause. 

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Related links

Alpha thalassemia
Beta thalassemia
Iron deficiency anemia
Microcytic anemia: Pathology review
Blood histology

Resources for research and reference

Forshaw J, Harwood L. Red blood cell abnormalities in cardiac valvular disease. J Clin Pathol. 1967;20(6):848-853. doi:10.1136/jcp.20.6.848

Gonzalez-Casas R, Jones EA, Moreno-Otero R. Spectrum of anemia associated with chronic liver disease. World J Gastroenterol. 2009;15(37):4653-4658. doi:10.3748/wjg.15.4653

Kaushansky K, Lichtman M, Prchal J, Levi M, Press O, Burns L, Caligiuri M. Williams Hematology. 9th ed. McGraw Hill; 2015.

National Center for Advancing Translational Sciences. Thalassemia. In GARD: Genetic and Rare Diseases Information Center. Published 2015. Accessed April 6, 2021.

National Heart, Lung, and Blood Institute. Hemolytic anemia. Published n.d. Accessed April 6, 2021.

Shastry I, Belurkar S. The spectrum of red blood cell parameters in chronic kidney disease: A study of 300 cases. J Appl Hematol. 2019;10(2):61-66. doi:10.4103/joah.joah_13_19

To M, Villatoro V. A laboratory guide to clinical hematology [eBook edition]. University of Alberta. Published 2019. Accessed April 6, 2021.