What is the recommended management for iron‑deficiency anemia confirmed by low hemoglobin with microcytosis, low ferritin and high total iron‑binding capacity, including first‑line oral iron regimen, indications for intravenous iron, transfusion thresholds, and treatment of the underlying cause?

Management of Iron‑Deficiency Anemia

Diagnostic Confirmation

Begin with serum ferritin as the single most powerful diagnostic test; a level <30 µg/L confirms depleted iron stores, while a cut‑off of 45 µg/L provides optimal sensitivity and specificity in routine practice. 1, 2

• Ferritin <15 µg/L yields 99% specificity for absolute iron deficiency and eliminates the need for further iron studies 1, 2
• When ferritin is 30–100 µg/L, measure C‑reactive protein and calculate transferrin saturation (TSAT = serum iron × 100 ÷ TIBC) because ferritin is an acute‑phase reactant that can be falsely elevated by inflammation, infection, malignancy, or liver disease 1, 2, 3
• TSAT <20% confirms iron deficiency even when ferritin appears normal due to inflammation 1, 2
• Microcytosis (MCV <80 fL) combined with elevated red‑cell distribution width (RDW >14%) strongly indicates iron deficiency rather than thalassemia trait, which typically shows RDW ≤14% 2

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First‑Line Oral Iron Therapy

Initiate oral ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least three months after hemoglobin normalization to fully replenish iron stores. 2

• Alternative formulations include ferrous gluconate or ferrous fumarate if ferrous sulfate is not tolerated 2
• Adding ascorbic acid (vitamin C) enhances iron absorption 2
• A hemoglobin rise ≥10 g/L within 2 weeks confirms iron deficiency even when initial iron studies are equivocal 1, 2
• Continue therapy until ferritin exceeds 50 µg/L to prevent rapid recurrence 2
• Monitor hemoglobin and red‑cell indices at three‑monthly intervals for one year, then after a further year 2

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Indications for Intravenous Iron

Switch to intravenous iron (iron sucrose, ferric carboxymaltose, or iron gluconate) when oral iron fails to raise hemoglobin by ≥2 g/dL within 4 weeks, malabsorption is documented, or gastrointestinal side effects prevent adherence. 2, 4

• Calculate the total cumulative dose using formulas for iron deficit (correcting hemoglobin deficit plus rebuilding stores), and administer in divided doses every 3–7 days until the total is given 1
• Maximum single dose should not exceed the product‑specific limit 1
• Monitor serum ferritin and keep it below 500 µg/L to avoid iron overload, especially in children and adolescents 1
• In iron‑refractory iron deficiency anemia (IRIDA) due to TMPRSS6 mutations, oral iron is typically ineffective; intravenous iron is required 1, 2, 4

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Transfusion Thresholds

Reserve red blood cell transfusion for hemodynamically unstable patients or those with symptomatic severe anemia (e.g., hemoglobin <7 g/dL with cardiac symptoms); transfusion is not a substitute for identifying and treating the underlying cause. 2

• In elderly patients with cardiac disease, target hemoglobin 7–9 g/dL to avoid volume overload 2
• Transfusion should be followed immediately by investigation for the bleeding source 2

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Investigation and Treatment of Underlying Cause

All adult men with hemoglobin <110 g/L and non‑menstruating women with hemoglobin <100 g/L warrant fast‑track gastrointestinal referral for bidirectional endoscopy (upper endoscopy with duodenal biopsies plus colonoscopy) because gastrointestinal malignancy is a critical concern. 1, 2

• Investigation should be considered at any anemia severity when iron deficiency is confirmed, as more severe anemia correlates with higher likelihood of serious GI pathology 1, 2
• Upper endoscopy with duodenal biopsies screens for celiac disease (present in 2–3% of iron‑deficiency cases), gastric cancer, peptic ulcer disease, and NSAID‑induced gastropathy 1, 2
• Colonoscopy detects colonic carcinoma, adenomatous polyps, angiodysplasia, and inflammatory bowel disease 1, 2
• In premenopausal women, heavy menstrual bleeding is the most common cause, but gastrointestinal evaluation is still required if menstrual loss does not fully account for the severity of anemia 2
• Screen for Helicobacter pylori infection and autoimmune atrophic gastritis, which impair iron absorption 2, 4

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Special Considerations and Pitfalls

• Do not attribute iron deficiency in adults solely to dietary inadequacy; occult gastrointestinal blood loss must be excluded 1, 2
• Do not rely on ferritin alone when inflammation is present; always calculate TSAT because functional iron deficiency can exist with high ferritin but low TSAT 1, 2, 3
• Do not discontinue iron supplementation once hemoglobin normalizes; stores must be replenished (target ferritin >50 µg/L) to prevent recurrence 2
• Do not overlook combined deficiencies; iron deficiency can coexist with vitamin B12 or folate deficiency, recognizable by elevated RDW 1, 2
• Order hemoglobin electrophoresis only after iron studies are normal or borderline, or when MCV is disproportionately low relative to anemia severity, to exclude thalassemia trait 2
• In patients with chronic kidney disease, chronic heart failure, or inflammatory bowel disease, use a ferritin threshold <100 µg/L (instead of <30 µg/L) to screen for iron deficiency 2, 3