From the Guidelines
An elevated Red Cell Distribution Width (RDW) without microcytosis is a significant finding that warrants further investigation, as it can indicate early iron deficiency, vitamin B12 or folate deficiency, or serve as a marker of underlying inflammation or chronic disease. When RDW is increased but mean corpuscular volume (MCV) remains normal, it represents heterogeneity in red blood cell size without the presence of predominantly small red cells. This pattern often appears before anemia develops and may be the earliest laboratory sign of nutritional deficiencies.
Key Considerations
- In early iron deficiency, RDW typically rises before MCV decreases, making it a sensitive early indicator 1.
- Similarly, in B12 or folate deficiency, RDW elevation may precede the development of macrocytosis.
- Beyond nutritional causes, elevated RDW is increasingly recognized as an independent predictor of mortality in various conditions including cardiovascular disease, sepsis, cancer, and chronic inflammatory states.
- The underlying mechanism involves inflammatory cytokines disrupting normal erythropoiesis, leading to greater variation in red cell size.
Recommended Approach
- When encountering this laboratory finding, clinicians should consider further evaluation with:
- Iron studies
- Vitamin B12 and folate levels
- Inflammatory markers
- Assessment for underlying chronic conditions based on the patient's clinical presentation
- A comprehensive workup may include a complete blood count with MCV, reticulocytes, serum ferritin, transferrin saturation, and CRP, as well as vitamin B12, folic acid, haptoglobin, and a differential white blood cell count 1.
From the Research
Significance of Elevated RDW without Microcytosis
- An elevated Red Cell Distribution Width (RDW) without microcytosis can be an indicator of various underlying conditions, including cardiovascular disease, venous thromboembolism, cancer, diabetes, and chronic obstructive pulmonary disease 2.
- The increased RDW value mirrors a profound deregulation of erythrocyte homeostasis, involving both impaired erythropoiesis and abnormal red blood cell survival, which may be attributed to metabolic abnormalities such as oxidative stress, inflammation, and poor nutritional status 2.
- Although RDW is traditionally used in laboratory hematology for differential diagnosis of anemias, its value is now being regarded as a strong and independent risk factor for death in the general population 2.
- Elevated RDW without microcytosis may also be associated with enhanced patient fragility and higher vulnerability to adverse outcomes, particularly in cardiovascular diseases 3.
- The diagnostic specificity of RDW is low, and its measurement is still plagued by important lack of standardization, but abnormal RDW values can persuade physicians to broaden the diagnostic reasoning over anemias and encompass a comprehensive assessment of traditional and non-traditional risk factors 3.
Clinical Applications and Limitations
- RDW can be a useful parameter in the differential diagnosis of mixed anemia, particularly when used in conjunction with other laboratory parameters such as reticulocyte count, mean corpuscular volume, and corpuscular mean hemoglobin concentration 4.
- However, the role of RDW in classifying microcytic hypochromic anemia is limited, with a sensitivity of 71.42% and specificity of 40% 5.
- RDW can be used to exclude iron deficiency in cases where serum ferritin concentration does not accurately reflect iron stores, but its value within the reference interval does not necessarily rule out other underlying conditions 6.