What are the implications of a slightly elevated RDW in an elderly patient with normal H&H?

Evaluation of Elevated RDW in a 72-Year-Old Female with Normal Hemoglobin and Hematocrit

In this 72-year-old female with normal H&H but elevated RDW (15.4%), low MCH (25.3), and low MCHC (31.0), you should be primarily concerned about early iron deficiency, occult gastrointestinal blood loss requiring endoscopic evaluation, and increased cardiovascular mortality risk, as elevated RDW is a strong independent predictor of death even in the absence of anemia. 1, 2, 3

Primary Diagnostic Concerns

Iron Deficiency Without Anemia

• The combination of low MCH and low MCHC with elevated RDW indicates microcytic, hypochromic red blood cells characteristic of iron deficiency, even when hemoglobin remains normal. 1
• High RDW (>14.5%) reflects increased variation in red cell size and is an early indicator of iron deficiency, often appearing before MCV changes become apparent. 1
• The elevated RBC count (5.26) with microcytosis creates a compensatory pattern where the bone marrow produces more cells to maintain normal hemoglobin despite iron-deficient erythropoiesis. 1

Mandatory Gastrointestinal Investigation

• All adult women (especially post-menopausal) with confirmed iron deficiency require both upper and lower endoscopy to exclude malignancy, regardless of hemoglobin level or symptom severity. 4, 1
• Even mild laboratory abnormalities warrant investigation, as severity does not correlate with likelihood of serious underlying disease. 4
• Occult gastrointestinal blood loss is the most common cause requiring thorough evaluation. 1

Cardiovascular Mortality Risk

• Elevated RDW (>14.5%) is a strong and independent risk factor for all-cause mortality in elderly patients, even in the absence of anemia. 2, 5, 3
• In hemodialysis patients, RDW proved to be a stronger predictor of mortality than traditional anemia markers including hemoglobin, ferritin, and iron saturation. 2
• The combination of elevated RDW with normal hemoglobin in elderly patients still confers increased mortality risk (HR = 3.66 in non-anemic patients). 5

Essential Diagnostic Workup

First-Line Laboratory Tests

• Serum ferritin (<30 μg/L confirms iron deficiency; <100 μg/L with inflammation) is the most powerful confirmatory test. 4, 1
• Transferrin saturation (<30% supports iron deficiency) provides additional iron store assessment. 4, 1
• C-reactive protein (CRP) to identify concurrent inflammation that may falsely elevate ferritin and mask iron deficiency. 4, 1
• Reticulocyte count to assess bone marrow response. 1

Additional Considerations

• Hemoglobin electrophoresis is NOT indicated here, as elevated RDW distinguishes iron deficiency from thalassemia trait (which typically has normal or only slightly elevated RDW). 4, 1
• Combined deficiencies (iron plus folate or B12) can result in normal MCV despite iron deficiency, so consider B12 and folate levels if ferritin is low. 4

Critical Clinical Pitfalls to Avoid

Do Not Delay Investigation

• Never assume normal hemoglobin excludes clinically significant iron deficiency or underlying pathology. 4, 1
• Do not empirically treat with iron without confirming iron deficiency with ferritin, as this can cause iron overload if thalassemia is present. 4
• Serum ferritin can be falsely elevated in inflammatory conditions, chronic disease, malignancy, or liver disease, potentially masking true iron deficiency. 1

Recognize Prognostic Implications

• Elevated RDW reflects profound deregulation of erythrocyte homeostasis involving impaired erythropoiesis, oxidative stress, inflammation, poor nutritional status, and altered erythropoietin function. 3
• RDW has high negative predictive value for diagnosing various disorders and conveys important information for short- and long-term prognosis in cardiovascular disease, venous thromboembolism, cancer, diabetes, pneumonia, COPD, and liver/kidney failure. 3
• In hospitalized older patients, RDW ≥15% is associated with longer hospital stays, worse prognosis, and higher in-hospital mortality. 6

Recommended Clinical Algorithm

1. Obtain serum ferritin, transferrin saturation, and CRP immediately to confirm iron deficiency and assess for inflammation. 4, 1

2. If ferritin <30 μg/L (or <100 μg/L with elevated CRP), proceed directly to bidirectional endoscopy (upper and lower) to exclude gastrointestinal malignancy. 4, 1

3. Assess cardiovascular risk factors given the independent mortality risk associated with elevated RDW in elderly patients, including evaluation for heart failure, coronary disease, and other comorbidities. 2, 5, 3

4. Consider B12 and folate levels if ferritin is low, as combined deficiencies may be present. 4

5. Initiate iron supplementation only after confirming iron deficiency and initiating gastrointestinal investigation. 4