Anisopoikilocytosis · What Is It, Causes, Diagnosis, and More

The most common causes of anisopoikilocytosis are blood disorders, like thalassemia and certain types of anemia, as well as other chronic disorders and nutritional deficiencies. Thalassemia is an inherited condition where the 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 greater concentration of hemoglobin in their center surrounded by a clear ring, which is further surrounded by a peripheral rim of hemoglobin. This gives them a target-like appearance, hence the name target cells, also known as codocytes.  

Types of anemia that can cause anisopoikilocytosis include iron deficiency, hemolytic, megaloblastic, and sickle cell. 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 cells with irregular shapes and sizes (i.e., schistocytes) due to the destruction of RBCs. 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 like severe aortic stenosis can cause irregular flows of circulating blood that can fragment RBCs as they pass through the narrowed valve opening. Similarly, prosthetic heart valves can create high shear forces, leading to damage of RBCs and the production of schistocytes. 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 as they can cause megaloblastic anemia. Chronic alcohol use disorder can also affect the formation of blood cells and result in anisopoikilocytosis.  

Anisopoikilocytosis can be diagnosed by a peripheral blood smear. A peripheral blood smear involves viewing a blood sample under a microscope to examine the size, shape, and other characteristics of blood cells. 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. It 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 to determine the cause of anisopoikilocytosis. 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. Treatment for iron deficiency anemia includes addressing the underlying cause (e.g., heavy menstruation, gastrointestinal bleeding, etc.) and giving oral iron supplements, like ferrous sulfate. These can be taken with orange juice, which is slightly acidic and can help absorption. If oral iron isn’t effective, intravenous iron can be used instead. For vitamin B12 or folate deficiency, vitamin B12 injections or oral supplements, and folate supplementation, are often prescribed.  

In individuals with hemoglobinopathies like sickle cell anemia or thalassemia, management focuses on supportive care, such as blood transfusions, folic acid supplements, and sometimes bone marrow transplantation for severe cases.  

For individuals with chronic disorders such as liver or kidney failure, management involves addressing the underlying condition and giving erythropoiesis-stimulating agents (e.g., epoetin, darbopoetin) for anemia of chronic kidney disease.