Given low serum iron, low ferritin, low transferrin saturation, high‑normal total iron‑binding capacity, and a normal reticulocyte percentage, what are the next steps in evaluation and management?

Management of Confirmed Absolute Iron Deficiency

Begin oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily (or alternate-day dosing), and concurrently screen for celiac disease and Helicobacter pylori while investigating the source of iron loss. 1

Laboratory Interpretation

Your results definitively confirm absolute iron deficiency:

• Ferritin 16 ng/mL falls below the diagnostic threshold of <30 µg/L and approaches the <15 µg/L cutoff that has 99% specificity for depleted iron stores 2, 1
• Iron saturation 8% is markedly below the 16% threshold, indicating severely impaired iron delivery to bone marrow for red blood cell production 2
• Serum iron 29 µg/dL is profoundly low, reflecting inadequate circulating iron 2
• TIBC 344 µg/dL (high-normal) represents the body's compensatory attempt to capture more circulating iron when stores are depleted 2
• Normal reticulocyte count 1.9% indicates the bone marrow is not yet mounting a regenerative response, consistent with iron-restricted erythropoiesis rather than active bleeding 2

The combination of low iron, low ferritin, low transferrin saturation, and high-normal TIBC is the classic laboratory signature of absolute iron deficiency before anemia develops. 2, 1

Immediate Treatment Protocol

Start Oral Iron Without Delay

• Initiate ferrous sulfate 65 mg elemental iron daily or consider 60–65 mg every other day; alternate-day dosing improves fractional absorption by 30–50% and reduces gastrointestinal side effects (nausea, constipation, diarrhea) 1
• Take on an empty stomach for optimal absorption, or with meals if gastrointestinal symptoms develop 1
• Expected response: hemoglobin should rise ≥10 g/L within 2 weeks of starting therapy; absence of this rise suggests malabsorption, non-compliance, or ongoing occult blood loss 1
• Continue supplementation for 3 months after hemoglobin normalizes to achieve target ferritin >100 ng/mL and prevent rapid recurrence 1

Mandatory Diagnostic Work-Up (Perform Concurrently with Treatment)

Screen for Malabsorption

• Order tissue transglutaminase IgA antibodies (tTG-IgA) to screen for celiac disease, which accounts for 3–5% of iron-deficiency cases and is a frequent cause of treatment failure when missed 1
• Perform non-invasive Helicobacter pylori testing (stool antigen or urea-breath test), as the organism impairs intestinal iron absorption 1

Identify the Source of Iron Loss

The diagnostic algorithm depends on patient demographics and symptoms:

For Adult Men or Post-Menopausal Women

• Urgent bidirectional endoscopy (upper gastroscopy + colonoscopy) is mandatory, because iron deficiency may be the sole presenting sign of gastrointestinal malignancy 1

For Premenopausal Women

• Assess menstrual blood loss history first, as heavy menses are the most common cause in this population 1
• Reserve bidirectional endoscopy for specific red flags:
  • Age ≥50 years (higher malignancy risk)
  • Gastrointestinal symptoms (abdominal pain, altered bowel habits, visible blood in stool)
  • Positive celiac or H. pylori testing requiring confirmation
  • Lack of hemoglobin response after 8–10 weeks of adequate oral iron
  • Strong family history of colorectal cancer 1
• For young women <50 years with heavy menses and no gastrointestinal symptoms, empiric oral iron supplementation without immediate endoscopy is appropriate 1

When to Switch to Intravenous Iron

Transition to intravenous ferric carboxymaltose (15 mg/kg, maximum 1000 mg per dose) if any of the following apply:

• Severe oral iron intolerance (marked nausea, constipation, or diarrhea preventing adherence)
• Confirmed malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery anatomy)
• Ongoing blood loss exceeding oral replacement capacity
• Lack of hemoglobin response after 8–10 weeks of adequate oral iron
• Chronic inflammatory conditions (chronic kidney disease, heart failure, cancer) 1

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

Follow-Up and Monitoring

• Repeat complete blood count and ferritin at 8–10 weeks to assess therapeutic response 1
• Target ferritin >100 ng/mL to fully replenish iron stores and prevent recurrence 1
• Persistent failure of ferritin to rise despite adequate supplementation signals ongoing occult blood loss or malabsorption and warrants urgent gastrointestinal evaluation 1
• For high-risk groups (menstruating females, vegetarians, endurance athletes), schedule ferritin screening every 6–12 months to detect early depletion before anemia develops 1

Critical Pitfalls to Avoid

• Do not wait for anemia to develop before treating; iron deficiency without anemia still causes significant symptoms including fatigue, reduced exercise tolerance, and impaired cognitive function 1
• Do not assume dietary modification alone will correct this degree of deficiency; supplementation is mandatory because dietary iron cannot replenish stores within a clinically acceptable timeframe 1
• Do not overlook celiac disease screening; its 3–5% prevalence among iron-deficiency cases means missing this diagnosis leads to treatment failure 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
• In adult men and post-menopausal women, do not delay endoscopic evaluation, as gastrointestinal malignancy can present solely with iron deficiency 1