What is the best management approach for a patient with iron deficiency but normal hemoglobin levels?

Management of Iron Deficiency with Normal Hemoglobin

All patients with confirmed iron deficiency should receive iron supplementation to replenish body stores, even when hemoglobin is normal. 1

Diagnostic Confirmation

Before initiating treatment, confirm iron deficiency with:

• **Serum ferritin <30 µg/L** for healthy males and females aged >15 years 2
• MCV <76 fL (if available) 1
• Exclude acute phase reaction by checking C-reactive protein, as inflammation falsely elevates ferritin despite true iron deficiency 2

For younger patients, use lower ferritin cut-offs: 15 µg/L for children 6-12 years and 20 µg/L for adolescents 12-15 years 2

Investigation for Underlying Cause

The extent of investigation depends on patient demographics and risk factors:

Patients >45 Years

• Upper GI endoscopy with small bowel biopsy AND colonoscopy or barium enema should be performed in 90% of cases unless an obvious cause is identified 1
• This aggressive approach is warranted due to increasing incidence of significant pathology with age 1

Patients <45 Years

• With upper GI symptoms: Perform endoscopy and small bowel biopsy 1
• Without upper GI symptoms: Check antiendomysial antibody (and IgA levels to exclude IgA deficiency) to screen for celiac disease 1
• Colonic investigation only if specific indications present 1

Premenopausal Women

• Iron deficiency occurs in 5-10% of menstruating women 1
• Menstrual loss, menorrhagia, pregnancy, and breastfeeding are usually responsible 1
• Consider pictorial blood loss assessment charts (80% sensitivity/specificity for menorrhagia) 1

Treatment Protocol

First-Line: Oral Iron Supplementation

Ferrous sulfate 200 mg three times daily is the simplest and most cost-effective option 1

Alternative oral preparations with equivalent efficacy:

• Ferrous gluconate 1
• Ferrous fumarate 1
• Liquid preparations when tablets are not tolerated 1

Add ascorbic acid if response is poor, as it enhances iron absorption 1

Duration of Treatment

Continue iron supplementation for three months after correction of laboratory values to replenish iron stores 1

Even with normal hemoglobin at baseline, the goal is to normalize ferritin and prevent progression to anemia 1

Monitoring Response

• Recheck hemoglobin, MCV, and ferritin at 8-10 weeks 2
• Hemoglobin should rise by 2 g/dL after 3-4 weeks if anemia develops during follow-up 1
• Failure to respond suggests poor compliance, misdiagnosis, continued blood loss, or malabsorption 1

Long-Term Follow-Up

• Monitor hemoglobin and red cell indices every 3 months for one year, then annually 1
• Repeat oral iron if hemoglobin or MCV falls below normal (check ferritin in doubtful cases) 1
• Patients with repeatedly low ferritin benefit from intermittent oral substitution and monitoring every 6-12 months 2

Parenteral Iron Therapy

Reserve intravenous iron for specific circumstances only:

• Intolerance to at least two oral preparations 1
• Non-compliance with oral therapy 1
• Concomitant disease requiring urgent treatment 2
• Repeated failure of oral therapy 2

Ferric carboxymaltose (Injectafer) allows delivery of up to 1,000 mg iron in a single 15-minute infusion 3, 4

For patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days (total 1,500 mg per course) 3

Critical Caveats

• Do NOT administer preventative iron when stores are normal - this is inefficient, causes side effects, and may be harmful 2
• Faecal occult blood testing has no benefit - it is insensitive and non-specific 1
• Gastrointestinal side effects are the primary cause of poor compliance with oral iron; using preparations with 28-50 mg elemental iron may improve tolerance 2
• Long-term daily supplementation with normal or high ferritin is potentially harmful and not recommended 2