Anisocytosis is a finding from a routine blood test that describes a variation in the size of a patient’s red blood cells. Normally, these oxygen-carrying cells maintain a uniform size to function optimally as they navigate the body’s smallest capillaries. The term itself is not a diagnosis but a sign that red blood cell production (erythropoiesis) is disrupted. Recognizing anisocytosis prompts a medical provider to investigate underlying conditions interfering with healthy blood cell maturation.
What Anisocytosis Means and How It Is Measured
Anisocytosis is quantified primarily through the Red Cell Distribution Width (RDW), a value reported on a complete blood count (CBC) test. The RDW measures the heterogeneity of red blood cell volume, showing how much the sizes of circulating cells deviate from the average size. A high RDW value confirms anisocytosis, indicating a greater mix of large and small cells than is typical.
The average size of red blood cells is measured separately by the Mean Corpuscular Volume (MCV), which helps interpret the RDW result. Red blood cells typically have an average volume between 80 and 100 femtoliters (fL). A high RDW coupled with a high or low MCV is a powerful diagnostic clue, suggesting a mixed population of cells, such as normally sized cells circulating alongside newly produced, abnormally sized cells.
When the MCV is low (below 80 fL), the average cell size is small, a condition known as microcytosis, which often accompanies a high RDW. Conversely, when the MCV is high (above 100 fL), the average cell size is large, termed macrocytosis, which also frequently presents with an elevated RDW. The RDW-CV (Coefficient of Variation) is the most common measurement, typically falling in a reference range between 11.5% and 15.4%.
Underlying Conditions That Cause Red Blood Cell Size Variation
The fundamental cause of anisocytosis is a defect in the bone marrow’s ability to produce a consistently sized red blood cell population. This size variation is commonly observed in various forms of anemia and other disorders affecting the building blocks or machinery of blood production.
Iron deficiency anemia is a primary cause of anisocytosis with microcytosis (small cells). The body lacks sufficient iron to synthesize adequate hemoglobin, the molecule responsible for oxygen transport. Red blood cell precursors compensate for the low hemoglobin concentration by undergoing extra cell divisions, resulting in the release of smaller-than-normal cells.
Deficiencies in Vitamin B12 and folate cause megaloblastic anemia, leading to anisocytosis with macrocytosis (large cells). These vitamins are necessary cofactors for DNA synthesis; their absence impairs the cell nucleus’s ability to divide while the cytoplasm continues to grow. This asynchronous maturation produces oversized red blood cell precursors that mature into large, often oval-shaped red blood cells.
Myelodysplastic syndromes (MDS) are bone marrow disorders that cause profound anisocytosis. This results from ineffective hematopoiesis, where genetic mutations in stem cells lead to the production of dysfunctional and morphologically abnormal red blood cells. MDS can present with both macrocytic and normocytic red cell populations, resulting in a significantly elevated RDW that reflects a wide spectrum of abnormally sized cells.
Chronic liver disease also frequently causes anisocytosis, often presenting with macrocytosis. This may be due to concurrent folate deficiency, which is common, or a direct effect of liver dysfunction. The accumulation of excess lipids and cholesterol on the red blood cell membrane can physically enlarge the cells, leading to a population of large, abnormally shaped cells.
Follow-Up Testing and Treatment
Once anisocytosis is identified via a high RDW, the next step involves a comprehensive review of the full CBC panel, especially the MCV and Mean Corpuscular Hemoglobin (MCH). This is followed by a peripheral blood smear, where a laboratory technician visually inspects the blood under a microscope. This microscopic examination confirms the size variation and identifies specific cell shapes—such as macro-ovalocytes or fragmented cells—that point toward a definitive diagnosis.
Targeted blood tests are then ordered to pinpoint the underlying cause, commonly measuring levels of ferritin (stored iron), serum iron, Vitamin B12, and folate. Identifying the cause dictates the management plan necessary to resolve the anisocytosis.
Treatment focuses on correcting the underlying disorder. Anisocytosis caused by nutritional deficiencies is typically managed with oral supplementation of iron or folate, or intramuscular injections of Vitamin B12, especially in cases of malabsorption. For macrocytosis related to chronic liver disease, treatment involves managing the liver condition and often includes alcohol abstinence. Patients with myelodysplastic syndromes may require supportive care, such as red blood cell transfusions or medications like erythropoiesis-stimulating agents (ESAs).