What is the evaluation and management for a patient with anemia and abnormal red blood cell indices, including Hemoglobin (Hb) and Hematocrit (Hct) levels, Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), and Red Cell Distribution Width (RDW)?

Evaluation and Management of Normocytic Anemia with Elevated RDW

This 23-year-old patient has normocytic anemia (Hb 14.1 g/dL is borderline low for males, normal for females; MCV 88.3 fL is normal) with low MCHC (29.6 g/dL) and elevated RDW (15.4%), which strongly suggests early iron deficiency or combined deficiency states that require immediate iron studies and inflammatory markers to guide specific treatment. 1

Understanding the Laboratory Pattern

The combination of normal MCV with elevated RDW is a critical red flag that can mask early iron deficiency or combined deficiency states where microcytosis and macrocytosis cancel each other out, resulting in a falsely normal MCV. 1 The low MCHC (29.6 g/dL, normal range typically 32-36 g/dL) further supports iron-restricted erythropoiesis even before frank microcytosis develops. 1

• The elevated RDW reflects abnormal erythropoiesis and may be the first indicator of iron deficiency before microcytosis becomes apparent. 1
• This pattern can also indicate early vitamin B12 or folate deficiency, hemolysis, or anemia of chronic disease with concomitant iron deficiency. 1

Essential Diagnostic Workup

Order the following tests immediately to establish the diagnosis:

First-Line Studies

• Serum ferritin and transferrin saturation to evaluate for iron deficiency—ferritin <30 μg/L confirms iron deficiency in the absence of inflammation. 1
• C-reactive protein (CRP) to detect inflammation, as this critically affects interpretation of iron studies. 2, 1
• Reticulocyte count to assess bone marrow response and distinguish between production versus destruction/loss. 1, 3
• Complete blood count with differential to evaluate other cell lines for additional abnormalities. 1

Interpretation Based on Inflammation Status

Without inflammation (normal CRP):

• Ferritin <30 μg/L confirms iron deficiency. 1
• Transferrin saturation <20% supports iron deficiency. 2

With inflammation present (elevated CRP):

• Ferritin up to 100 μg/L can still be consistent with iron deficiency due to ferritin's acute phase reactant properties. 2, 1
• Consider checking reticulocyte hemoglobin content (CHr) or soluble transferrin receptor if available, as these are less affected by inflammation. 2

Additional Testing if Initial Studies Are Inconclusive

• Vitamin B12 and folate levels if combined deficiency is suspected. 1
• Thyroid function tests as thyroid dysfunction can cause anemia. 2, 1
• Peripheral blood smear to evaluate for hemolysis or other morphologic abnormalities. 3

Management Strategy

If Iron Deficiency Is Confirmed

Initiate oral iron supplementation immediately while investigating the source of iron loss. 2

• Ferrous sulfate 200 mg three times daily is the first-line treatment, though ferrous gluconate and ferrous fumarate are equally effective. 2
• Recent evidence supports alternate-day dosing to avoid hepcidin-mediated absorption blockade, which may improve tolerance and efficacy. 2
• Continue iron therapy for 3 months after correction of anemia to replenish body stores. 2

For a 23-year-old patient, investigate for gastrointestinal blood loss:

• In premenopausal women, menstrual loss is common (5-10% prevalence), but GI pathology must still be excluded if dietary deficiency is not obvious. 2
• Upper GI endoscopy with small bowel biopsies (to screen for celiac disease, which occurs in 2-3% of iron deficiency anemia patients). 2
• Colonoscopy should follow unless upper endoscopy reveals cancer or celiac disease, as dual pathology occurs in ~10% of cases. 2
• Stop NSAIDs if being used, as they are a common cause of occult GI blood loss. 2

If Oral Iron Fails or Is Not Tolerated

Consider intravenous iron if:

• The patient cannot tolerate at least two oral iron preparations. 2
• There is malabsorption (e.g., celiac disease, inflammatory bowel disease). 2
• No response after 3-4 weeks of adequate oral iron therapy. 2

If Anemia of Chronic Disease Is Suspected

Address the underlying inflammatory condition as this is crucial for anemia resolution. 1

• Avoid empirical iron supplementation without confirmed deficiency, as it may be ineffective and potentially harmful. 1
• If ferritin is >100 μg/L with normal CRP, iron deficiency is unlikely. 2, 1

Follow-Up and Monitoring

Monitor hemoglobin and red cell indices closely:

• Recheck complete blood count after 4-6 weeks of iron therapy to assess response. 1
• Once normalized, monitor every 3 months for 1 year, then annually. 2
• Repeat iron studies if hemoglobin or MCV falls below normal during follow-up. 2

If anemia persists despite appropriate treatment or transfusion dependence develops:

• Consider further GI investigation including enteroscopy for small bowel evaluation. 2
• Refer to hematology for evaluation of less common causes including hemoglobinopathies, thalassemia, or bone marrow disorders. 1, 3

Critical Pitfalls to Avoid

• Do not assume dietary deficiency alone in a young adult without confirming and treating it, as GI pathology may coexist. 2
• Do not rely on fecal occult blood testing—it is insensitive and non-specific for iron deficiency evaluation. 2
• Do not miss celiac disease—always obtain small bowel biopsies during upper endoscopy. 2
• Do not interpret ferritin in isolation—always consider inflammatory status when ferritin is 15-100 μg/L. 2, 1