How to treat iron deficiency anemia with normal hematocrit (Hct) and hemoglobin (Hb) levels?

Iron Deficiency Without Anemia: Treatment Approach

Even when hemoglobin and hematocrit are normal, iron deficiency should be treated with oral iron supplementation to replenish depleted iron stores and prevent progression to anemia. 1

Confirming True Iron Deficiency

Before initiating treatment, confirm iron deficiency with:

• Serum ferritin <15 µg/L (or <30 µg/L in adults >15 years per some recommendations) 1, 2
• Low MCV (<76 fL) even with normal hemoglobin 1
• Exclude inflammatory conditions that falsely elevate ferritin by checking C-reactive protein 2

This scenario represents pre-anemic iron deficiency or early iron deficiency where stores are depleted but hemoglobin production has not yet been compromised 2.

Treatment Protocol

First-Line: Oral Iron Supplementation

All patients with confirmed iron deficiency should receive oral iron supplementation to replenish body stores, regardless of hemoglobin level. 1

Recommended regimen:

• Ferrous sulfate 200 mg once or twice daily (provides 65 mg elemental iron per dose) 1
• Alternative ferrous salts (ferrous gluconate, ferrous fumarate) are equally effective 1
• Lower doses (28-50 mg elemental iron) may improve tolerability with comparable efficacy 1, 2

Duration of therapy:

• Continue for 3 months after correction of iron indices to adequately replenish iron stores 1
• This extended duration is critical even when hemoglobin normalizes quickly 1

Enhancing Absorption and Tolerability

• Ascorbic acid 250-500 mg twice daily with iron may enhance absorption, though data on clinical effectiveness are limited 1
• Consider alternate-day dosing if gastrointestinal side effects occur, as this maintains efficacy while reducing adverse effects 1
• Ferric maltol 30 mg twice daily is a newer lipophilic formulation with better GI tolerability, though more expensive 1, 3

Monitoring Response

Check hemoglobin, hematocrit, MCV, and ferritin at 8-10 weeks after initiating therapy 2:

• Expect hemoglobin rise of at least 10 g/L after 2 weeks if anemia develops 1
• Failure to respond suggests non-compliance, malabsorption, continued blood loss, or misdiagnosis 1

Long-term follow-up:

• Monitor every 3 months for 1 year, then annually 1
• Resume oral iron if ferritin or MCV falls below normal 1

When to Consider Parenteral Iron

Reserve intravenous iron for specific circumstances 1:

• Intolerance to at least two oral preparations 1
• Documented malabsorption 1, 4
• Urgent need for rapid repletion 2

Available IV formulations include iron sucrose, ferric carboxymaltose, and iron dextran, with varying safety profiles and infusion requirements 1.

Investigating the Underlying Cause

The presence of iron deficiency—even without anemia—warrants investigation for the source of iron loss 1:

• Men and postmenopausal women: Require upper and lower GI endoscopy to exclude malignancy 1, 5
• Premenopausal women <50 years: Screen for celiac disease; reserve endoscopy for those with GI symptoms, family history of colorectal cancer, or persistent deficiency despite treatment 1
• Check for dietary deficiency, NSAID use, and menstrual losses 1

Critical Pitfalls to Avoid

• Do not ignore iron deficiency just because hemoglobin is normal—depleted stores cause fatigue, impaired cognition, and reduced physical performance even before anemia develops 2
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 1
• Do not use prophylactic iron in patients with normal ferritin—this is ineffective and potentially harmful 2
• Do not rely on fecal occult blood testing—it is insensitive and non-specific for investigating iron deficiency 1