What is the diagnosis and appropriate treatment for a patient with serum iron 26 µg/dL, unsaturated iron‑binding capacity 305 µg/dL, total iron‑binding capacity 331 µg/dL, transferrin saturation 7.9 %, and ferritin 9.2 ng/mL?

Severe Absolute Iron Deficiency Requiring Immediate Treatment and Investigation

This patient has severe absolute iron deficiency confirmed by ferritin 9.2 ng/mL (far below the 15 ng/mL threshold with 99% specificity) and transferrin saturation 7.9% (well below the 16% diagnostic cutoff), requiring immediate oral iron supplementation and mandatory investigation for the underlying cause of iron loss. 1

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Laboratory Interpretation

• Ferritin 9.2 ng/mL definitively confirms absolute iron deficiency, as values <15 µg/L have 99% specificity for depleted iron stores. 1
• Transferrin saturation 7.9% indicates severely impaired iron delivery to the bone marrow for red blood cell production; the diagnostic threshold is <16% in adults. 1
• Elevated TIBC 331 µg/dL and UIBC 305 µg/dL reflect the body's compensatory attempt to maximize iron-binding capacity when stores are depleted. 1
• Serum iron 26 µg/dL is markedly low, though serum iron alone has poor diagnostic accuracy due to high day-to-day variability and should not be used in isolation. 1

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Immediate Treatment: Oral Iron Supplementation

• Start ferrous sulfate 65 mg elemental iron daily (or 60–65 mg every other day) immediately; alternate-day dosing improves fractional absorption by 30–50% and reduces gastrointestinal side effects (nausea, constipation, diarrhea). 1
• Expected hematologic response: hemoglobin should rise by ≥10 g/L within 2 weeks of adequate therapy; absence of this rise suggests malabsorption, non-compliance, or ongoing blood loss. 1
• Continue oral iron for 3 months after hemoglobin normalizes to achieve target ferritin >100 ng/mL and fully restore iron reserves. 1
• Take iron on an empty stomach (≥1 hour before or ≥2 hours after meals) to maximize absorption, or with meals if gastrointestinal symptoms occur. 1

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Mandatory Investigation for Underlying Cause

All Adults (Men and Postmenopausal Women)

• Bidirectional endoscopy (upper GI gastroscopy + colonoscopy) is mandatory because iron deficiency may be the sole manifestation of gastrointestinal malignancy. 1
• Screen for celiac disease with tissue transglutaminase IgA antibodies; celiac disease accounts for 3–5% of iron-deficiency cases and causes treatment failure if missed. 1
• Test for Helicobacter pylori infection (stool antigen or urea-breath test) because the organism impairs iron absorption. 1

Premenopausal Women

• Assess menstrual blood loss history (soaking through a pad or tampon every 1–2 hours, or periods lasting >7 days), as heavy menstrual bleeding is the most common cause in this population. 1
• Perform celiac disease and H. pylori screening as above. 1
• Reserve bidirectional endoscopy for:
  • Age ≥50 years (higher malignancy risk) 1
  • Gastrointestinal symptoms (abdominal pain, altered bowel habits, visible blood) 1
  • Positive celiac or H. pylori testing requiring confirmation 1
  • Lack of response to adequate oral iron after 8–10 weeks 1
  • Strong family history of colorectal cancer 1

Additional Considerations

• Obtain complete blood count to assess for anemia, microcytosis (low MCV), and hypochromia (low MCH). 1
• Measure C-reactive protein (CRP) to identify concurrent inflammation, which can falsely elevate ferritin and mask true iron deficiency. 1
• Assess dietary intake for low heme iron (vegetarian/vegan diets), as non-heme iron is less efficiently absorbed. 1
• Evaluate for chronic kidney disease by calculating estimated glomerular filtration rate (eGFR), as CKD contributes to both iron deficiency and anemia. 1

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Indications for Switching to Intravenous Iron

Switch to intravenous ferric carboxymaltose (15 mg/kg, maximum 1000 mg per dose) when any of the following apply: 1, 2

• Gastrointestinal intolerance to oral iron (marked nausea, constipation, diarrhea) 1
• Confirmed malabsorption syndromes (celiac disease, inflammatory bowel disease, post-bariatric surgery) 1
• Ongoing blood loss exceeding oral replacement capacity 1
• Lack of hematologic response after 8–10 weeks of adequate oral iron therapy 1
• Chronic kidney disease with eGFR <30 mL/min/1.73 m² 1
• Chronic inflammatory conditions (heart failure, cancer) 1
• Pregnancy in the second/third trimester 1

Intravenous iron produces reticulocytosis within 3–5 days and yields a mean hemoglobin increase of ≈8 g/L over 8 days, demonstrating superior efficacy in the indicated populations. 1

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Monitoring and Follow-Up

• Repeat complete blood count and ferritin at 8–10 weeks after initiating oral iron to assess therapeutic response. 1
• Do not measure iron parameters within 4 weeks of IV iron infusion, as circulating iron can falsely elevate results. 1
• Target ferritin ≥100 ng/mL to ensure sufficient iron stores and prevent recurrence. 1
• Target transferrin saturation ≥20% to confirm adequate iron availability for erythropoiesis. 1
• For high-risk groups (menstruating females, vegetarians, athletes), schedule ferritin screening every 6–12 months to detect early depletion before anemia develops. 1

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Critical Pitfalls to Avoid

• Do not rely on "normal" serum iron to exclude deficiency; ferritin and transferrin saturation are far more reliable diagnostic markers. 1
• Do not assume ferritin will normalize spontaneously; dietary iron alone is insufficient to replenish stores within a clinically acceptable timeframe. 1
• Do not discontinue iron therapy once hemoglobin normalizes; an additional 3 months of supplementation is required for ferritin to reach >100 ng/mL. 1
• Do not overlook celiac disease screening, given its 3–5% prevalence among iron-deficiency cases; missing this diagnosis leads to treatment failure. 1
• Do not delay endoscopic evaluation in high-risk patients (age ≥50, alarm symptoms, treatment failure), as gastrointestinal malignancy can present solely with iron deficiency. 1