What is the recommended management for a 53-year-old female with microcytic anemia, elevated TIBC, normal to slightly elevated ferritin, and a low reticulocyte count, who denies any bleeding?

Management of Microcytic Anemia with Elevated Ferritin

This patient requires investigation for anemia of chronic disease or functional iron deficiency, followed by bidirectional endoscopy (upper and lower GI) to exclude occult gastrointestinal pathology, as the combination of microcytic anemia (MCV 63), elevated TIBC (342), and ferritin of 155 μg/L suggests either concurrent inflammation masking iron deficiency or a mixed picture that warrants complete evaluation. 1

Diagnostic Interpretation

The laboratory pattern presents a diagnostic challenge:

• Microcytosis (MCV 63) with elevated RDW (17.1) strongly suggests iron deficiency, as the elevated RDW indicates a heterogeneous red cell population typical of evolving iron deficiency 1, 2
• Ferritin 155 μg/L appears to exclude absolute iron deficiency, since ferritin >100 μg/L makes iron deficiency "almost certainly not present" in the absence of inflammation 1
• However, elevated TIBC (342) paradoxically suggests iron deficiency, as TIBC rises when the body attempts to maximize iron transport capacity 3, 2
• The low reticulocyte count (1.5%) indicates inadequate bone marrow response, which can occur in both iron deficiency and anemia of chronic disease 4, 5

Critical Diagnostic Consideration

The key issue is whether inflammation is present and falsely elevating ferritin:

• In the presence of chronic inflammation, malignancy, or hepatic disease, ferritin can be elevated despite true iron deficiency, though ferritin >100 μg/L typically excludes iron deficiency 1
• A ferritin cut-off of 45 μg/L provides optimal sensitivity/specificity for iron deficiency in practice, but up to 100 μg/L may still indicate iron deficiency when inflammation coexists 1, 6
• Transferrin saturation <16-20% would confirm functional or absolute iron deficiency despite the elevated ferritin 1, 6

Immediate Next Steps

Order the following tests immediately:

• Transferrin saturation (calculated from serum iron and TIBC) - if <20%, this confirms iron deficiency despite the ferritin level 1, 6
• C-reactive protein (CRP) to assess for occult inflammation that could be elevating ferritin 1, 4
• Hemoglobin electrophoresis to exclude thalassemia trait, particularly if the patient has appropriate ethnic background (Mediterranean, Asian, African descent) 1, 2

Investigation for Underlying Cause

In a 53-year-old postmenopausal female with microcytic anemia who denies bleeding, gastrointestinal investigation is mandatory:

• Both upper endoscopy with duodenal biopsies and colonoscopy are required, as occult GI blood loss from malignancy is the primary concern in this demographic 1
• Asymptomatic gastric and colonic carcinoma commonly present with iron deficiency anemia in postmenopausal women 1
• Duodenal biopsies during upper endoscopy are essential to exclude celiac disease, a common cause of iron malabsorption 1
• The British Society of Gastroenterology guidelines state that investigation should be considered at any level of anemia with confirmed iron deficiency, with stronger indication for more severe degrees 1

Treatment Algorithm

While awaiting endoscopy results:

• Initiate oral iron therapy with ferrous sulfate 200 mg three times daily as a therapeutic trial 6, 3
• A hemoglobin rise of ≥10 g/L (≥1 g/dL) within 2 weeks confirms iron-responsive anemia 6
• If no response occurs within 2-4 weeks, consider malabsorption, ongoing blood loss, non-compliance, or anemia of chronic disease 6, 4

If transferrin saturation confirms iron deficiency but oral iron fails:

• Switch to intravenous iron (iron sucrose or ferric gluconate) if malabsorption is documented 6, 5
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of IV iron 6

Common Pitfalls to Avoid

• Do not assume ferritin >100 μg/L excludes iron deficiency in all cases - inflammation, malignancy, or liver disease can falsely elevate ferritin while true iron deficiency persists 1
• Do not skip GI investigation in postmenopausal women - even without overt bleeding, occult GI malignancy must be excluded 1
• Do not overlook celiac disease - it is a common and treatable cause of iron deficiency that requires duodenal biopsy for diagnosis 1
• Do not diagnose thalassemia trait without hemoglobin electrophoresis - microcytosis with normal iron studies requires confirmation 1, 2

Special Considerations

• Anemia of chronic disease presents with low iron, low TIBC, and normal-to-elevated ferritin, which partially fits this patient's profile except for the elevated TIBC 4, 2
• Mixed iron deficiency and anemia of chronic disease can occur, where the elevated RDW and TIBC suggest superimposed iron deficiency on an inflammatory process 1, 4
• NSAID use, even if not reported, should be specifically queried as it is a common cause of occult GI blood loss 1