Clinical Significance of Elevated Red Blood Cell Distribution Width (RDW)
An elevated Red Blood Cell Distribution Width (RDW) is a powerful indicator of underlying pathology with significant prognostic implications across multiple conditions, particularly iron deficiency anemia, cardiovascular disease, and other chronic inflammatory states.
Definition and Measurement
RDW is calculated by dividing the standard deviation of red blood cell volume by the mean corpuscular volume (MCV) and multiplying by 100 to express the result as a percentage:
RDW (%) = {SD of red blood cell volume (fL)/MCV (fL)} x 100
A high RDW is generally defined as greater than 14.0%, which corresponds to the 95th percentile in reference populations 1. The specific value may vary slightly depending on the laboratory instrument used.
Diagnostic Significance
Iron Deficiency Anemia
- RDW is particularly useful when evaluated alongside MCV:
This distinction is clinically important as it helps differentiate between conditions requiring different management approaches.
Differential Diagnosis of Microcytic Anemias
The following pattern helps distinguish between common causes of microcytic anemia:
| Parameter | Iron Deficiency | Thalassemia Trait | Anemia of Chronic Disease |
|---|---|---|---|
| MCV | Low | Very low (<70 fl) | Low/Normal |
| RDW | High (>14%) | Normal (≤14%) | Normal/Slightly elevated |
| Ferritin | Low (<30 μg/L) | Normal | Normal/High |
| Transferrin saturation | Low | Normal | Low |
| RBC count | Normal/Low | Normal/High | Normal/Low |
Beyond Anemia
Elevated RDW has significant clinical implications beyond hematological disorders:
- Cardiovascular Disease: Serves as an independent risk factor for mortality in patients with coronary artery disease, heart failure, and those undergoing percutaneous coronary intervention 3, 4
- Chronic Conditions: Associated with poorer outcomes in chronic kidney disease, liver failure, and respiratory disorders 5
- General Mortality Risk: Recognized as a strong and independent risk factor for death in the general population 5
Prognostic Significance
Cardiovascular Disease
- In patients undergoing percutaneous coronary intervention with normal hemoglobin levels (>12.7 g/dL), high RDW was associated with an 8.6-fold increased risk of mortality compared to those with low RDW 4
- In chronic heart failure, a rising RDW over time predicts enhanced all-cause mortality (HR 9.27 for 1% per week rise) independently of baseline RDW 6
Evolving Iron Deficiency
The combination of rising RDW with falling MCV over time ("evolving iron deficiency") is associated with a 2.78-fold increased risk of mortality in heart failure patients, even worse than a rising RDW alone 6
Pathophysiological Mechanisms
Elevated RDW reflects profound deregulation of erythrocyte homeostasis that may be attributed to:
- Impaired erythropoiesis
- Abnormal red blood cell survival
- Oxidative stress
- Inflammation
- Poor nutritional status
- Dyslipidemia
- Hypertension
- Erythrocyte fragmentation
- Alteration of erythropoietin function 5
Clinical Approach to Elevated RDW
Evaluate for iron deficiency:
- Check serum ferritin (most powerful test for iron deficiency)
- Assess transferrin saturation (should be <30% in iron deficiency) 1
Consider other causes based on MCV:
- If microcytic: Evaluate for thalassemia, lead poisoning, anemia of chronic disease
- If normocytic: Consider hemorrhage, hemolysis, bone marrow failure, renal insufficiency
- If macrocytic: Investigate B12/folate deficiency 1
Assess for underlying conditions:
- Cardiovascular disease
- Chronic inflammatory conditions
- Malignancy
- Renal or hepatic dysfunction
Common Pitfalls
- Overlooking RDW in normocytic anemia: Even with normal MCV, elevated RDW can indicate early iron deficiency or mixed nutritional deficiencies
- Failing to trend RDW over time: Changes in RDW can have greater prognostic significance than a single elevated value
- Ignoring RDW in non-anemic patients: Elevated RDW has prognostic significance even in patients with normal hemoglobin levels
- Attributing elevated RDW solely to anemia: Consider broader implications for cardiovascular risk and overall mortality
Conclusion
RDW is far more than just a parameter for differentiating anemias. Its elevation serves as an important marker of physiological stress with significant diagnostic and prognostic implications across multiple disease states. Clinicians should recognize elevated RDW as a red flag warranting thorough investigation, even when hemoglobin levels are normal.