What is the optimal treatment for iron deficiency without anemia in a patient with ferritin 8 µg/L, normal hemoglobin, and low mean corpuscular volume and mean corpuscular hemoglobin?

Treatment of Iron Deficiency Without Anemia

Start oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (or alternate-day dosing to improve absorption and reduce side effects), and simultaneously screen for celiac disease with tissue transglutaminase antibodies. 1, 2, 3

Understanding Your Laboratory Pattern

Your presentation is classic for absolute iron deficiency without anemia:

• Ferritin 8 µg/L is far below the diagnostic threshold of <15 µg/L, which has 99% specificity for absolute iron deficiency—this definitively confirms depleted iron stores 1, 2
• Low MCV and MCH indicate microcytic hypochromic red cell indices, reflecting iron-restricted erythropoiesis even before anemia develops 1
• Normal hemoglobin means you are in Stage 1 iron deficiency, where stores are exhausted but anemia has not yet manifested 2, 3

This pattern requires treatment now to prevent progression to iron-deficiency anemia and to address symptoms like fatigue, exercise intolerance, and difficulty concentrating that occur even without anemia 3.

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Immediate Treatment Protocol

Oral Iron Supplementation (First-Line)

• Start ferrous sulfate 65 mg elemental iron daily (equivalent to one 325 mg ferrous sulfate tablet) 1, 2, 3
• Alternate-day dosing (60-65 mg every other day) may improve absorption by 30-50% and reduce gastrointestinal side effects compared to daily dosing 1, 2
• Take on an empty stomach for optimal absorption, or with meals if nausea, constipation, or diarrhea occur 2
• Expected response: hemoglobin should rise ≥10 g/L within 2 weeks if iron deficiency is the sole cause 1, 2

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Essential Concurrent Investigation

You must identify and address the source of iron loss while treating:

Mandatory Screening Tests

• Screen for celiac disease with tissue transglutaminase antibodies (tTG-IgA), as celiac disease is present in 3-5% of iron deficiency cases and will cause treatment failure if missed 1, 2
• Test for Helicobacter pylori non-invasively (stool antigen or urea breath test), as it impairs iron absorption 1, 2
• Assess menstrual blood loss history if you are a premenopausal woman, as heavy menses are the most common cause in this population 2, 3

When to Pursue Gastrointestinal Investigation

Reserve bidirectional endoscopy (upper and lower GI) for: 1, 2

• Age ≥50 years (higher risk of GI malignancy)
• Any gastrointestinal symptoms (abdominal pain, change in bowel habits, blood in stool)
• Positive celiac or H. pylori testing requiring confirmation
• Failure to respond to adequate oral iron therapy after 8-10 weeks
• Strong family history of colorectal cancer

For premenopausal women <50 years with heavy menses and no GI symptoms, empiric iron supplementation alone is reasonable without immediate endoscopy 1, 2.

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Follow-Up and Monitoring

• Repeat complete blood count and ferritin at 8-10 weeks to assess response 2, 3
• Target ferritin >100 ng/mL to fully restore iron stores and prevent recurrence 2
• If no improvement after 8-10 weeks, consider malabsorption (celiac disease, post-bariatric surgery), non-compliance, ongoing blood loss, or need for intravenous iron 2, 3

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When to Use Intravenous Iron Instead

Intravenous iron (ferric carboxymaltose 15 mg/kg, max 1000 mg per dose) is indicated if: 1, 4, 3

• Oral iron intolerance (severe nausea, constipation, diarrhea)
• Impaired iron absorption (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Ongoing blood loss that exceeds oral iron replacement capacity
• Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer)
• Pregnancy (second and third trimesters)

Intravenous iron produces a reticulocytosis at 3-5 days and mean hemoglobin increase of 8 g/L over 8 days, making it more effective than oral iron in these specific populations 1, 4.

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Critical Pitfalls to Avoid

• Do not assume normal hemoglobin means no treatment is needed—iron deficiency without anemia causes significant symptoms (fatigue, exercise intolerance, restless legs syndrome) and requires treatment 2, 3
• Do not continue daily iron supplementation indefinitely once ferritin normalizes, as chronic iron excess is potentially harmful 2
• Do not overlook celiac disease screening—it is present in 3-5% of iron deficiency cases and will cause treatment failure if not identified 1, 2
• Do not delay treatment while awaiting investigation results—start oral iron immediately and investigate concurrently 2, 3

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Long-Term Management

• For high-risk groups (menstruating females, vegetarians, athletes, regular blood donors), screen ferritin every 6-12 months to detect recurrence early 2, 3
• Address dietary iron intake: encourage heme iron sources (red meat, poultry, fish) and non-heme iron sources (legumes, fortified cereals) with vitamin C to enhance absorption 3