What is anisocytosis?

Anisocytosis: Definition and Clinical Significance

Anisocytosis is the medical term for increased variation in red blood cell size, which can be detected through laboratory testing and is an important indicator of various hematological disorders. 1

Definition and Measurement

• Anisocytosis represents the degree of heterogeneity in erythrocyte volume and is conventionally measured by the Red Cell Distribution Width (RDW) on automated blood analyzers 2
• RDW is a quantitative measure that provides a more precise assessment of red cell size variability compared to visual inspection of blood films 3
• In laboratory practice, RDW has become the "gold standard" for measuring red blood cell size variability due to its precision and objectivity 3
• Anisocytosis can be observed on peripheral blood smears as variable-sized red blood cells, but automated analysis provides more consistent results 1

Clinical Significance

• Anisocytosis is a common finding in various types of anemia and can help in differential diagnosis 1
• It is one of the earliest detectable hematological abnormalities in iron deficiency, often appearing before changes in hemoglobin concentration 4
• The degree of anisocytosis typically increases with progressive anemia, particularly in nutritional deficiencies like B12 and folate deficiency 5
• In cases with multiple deficiencies (such as combined B12 and folate deficiency), anisocytosis may be markedly increased out of proportion to the degree of anemia 5

Diagnostic Value in Different Anemias

• In iron deficiency anemia, anisocytosis and microcytosis are often the first hematological abnormalities to appear, even when hemoglobin concentration is still normal 4
• In macrocytic anemias (B12/folate deficiency), increased anisocytosis correlates with the severity of anemia 5
• In anemia of chronic disease, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) may be normal or low, with variable anisocytosis 1
• A high RDW with normal MCV may indicate early iron deficiency or combined nutritional deficiencies 1, 4

Diagnostic Workup

• Anemia workup should include red blood cell indices such as RDW and MCV, reticulocyte count, differential blood cell count, serum ferritin, transferrin saturation, and CRP concentration 1
• A wide size range of red cells (high RDW) is particularly helpful when microcytosis and macrocytosis co-exist, neutralizing each other and resulting in a normal MCV 1
• In iron deficiency, transferrin saturation less than 16% and/or serum ferritin less than 30 μg/L (or up to 100 μg/L in the presence of inflammation) are diagnostic criteria 1
• The minimum workup for anemia should include complete blood count with MCV, reticulocytes, serum ferritin, transferrin saturation, and CRP 1

Beyond Anemia: Broader Clinical Applications

• Beyond hematology, increased RDW has been associated with cardiovascular diseases, venous thromboembolism, cancer, diabetes, and chronic inflammatory conditions 2, 6
• An increased RDW has emerged as a strong and independent risk factor for mortality in the general population 2
• Abnormal RDW values should prompt physicians to consider a comprehensive assessment of both traditional and non-traditional cardiovascular risk factors 6
• The underlying mechanisms for increased RDW in various conditions may include oxidative stress, inflammation, poor nutritional status, and alterations in erythropoiesis 2

Common Pitfalls and Considerations

• RDW lacks diagnostic specificity when used alone and should be interpreted alongside other hematological parameters 6
• Laboratory standardization of RDW measurement remains an issue, with potential variations between different analyzers 6
• Age, sex, and ethnicity can influence normal RDW values, which should be considered when interpreting results 2
• In patients with multiple nutritional deficiencies, the pattern of anisocytosis may be complex and require comprehensive evaluation 5