What is the best course of treatment for a patient with low ferritin levels and normal iron binding capacity to replenish iron stores and prevent iron deficiency anemia?

Treatment of Low Ferritin with Normal Iron Binding Capacity

All patients with low ferritin should receive oral iron supplementation to replenish depleted iron stores, regardless of normal iron saturation or hemoglobin levels, as low ferritin represents true iron deficiency requiring treatment. 1

Understanding the Clinical Picture

Low ferritin with normal iron saturation represents early-stage iron deficiency where body iron stores are depleted but functional iron remains adequate—ferritin is the earliest and most specific indicator of depleted iron stores. 1 Normal transferrin saturation does not exclude the need for treatment when ferritin is low, as this pattern indicates iron stores are exhausted before functional iron becomes compromised. 1

A critical pitfall to avoid: Do not withhold iron supplementation based on normal iron saturation alone when ferritin is low—this represents true iron deficiency requiring treatment. 1

First-Line Treatment Protocol

Oral Iron Supplementation

Start ferrous sulfate 200 mg three times daily (approximately 65 mg elemental iron per dose), which is the most cost-effective and evidence-based first-line therapy. 2 Alternative ferrous salts including ferrous gluconate and ferrous fumarate are equally effective. 2

If the standard regimen is not tolerated, use preparations with 28-50 mg elemental iron content to prevent reduced compliance from gastrointestinal side effects. 3 Recent evidence supports alternate-day dosing (every other day) for better absorption and fewer gastrointestinal side effects. 1, 4

Enhancing Absorption

Add vitamin C 500 mg with each iron dose to enhance absorption, particularly if initial response is suboptimal. 2, 1 Ascorbic acid enhances iron absorption and should be considered when response is poor. 2

Take iron on an empty stomach when possible to enhance absorption, though this may increase gastrointestinal side effects. 1 Avoid taking iron with calcium supplements, antacids, or tea/coffee as these inhibit absorption. 1

Duration and Monitoring

Continue oral iron supplementation for 3 months after ferritin normalizes to adequately replenish body iron stores. 2, 1 Total treatment duration typically ranges from 3-6 months depending on baseline ferritin levels and response. 1

Recheck ferritin and complete blood count after 8-10 weeks of treatment, not earlier, as ferritin levels may be falsely elevated immediately after iron supplementation. 1, 3 The hemoglobin concentration should rise by 2 g/dL after 3-4 weeks if anemia is present. 2

After normalization, monitor ferritin every 3 months for one year, then after a further year. 2, 1 Additional oral iron should be given if ferritin falls below normal. 2

When to Use Intravenous Iron

Intravenous iron should be used if the patient does not tolerate oral iron, ferritin levels do not improve with a trial of oral iron, or the patient has a condition in which oral iron is not likely to be absorbed. 2

Specific indications include:

• Intolerance to at least two different oral iron preparations 2, 1
• Malabsorption conditions (celiac disease, post-bariatric surgery) 2, 5
• Chronic inflammatory conditions (inflammatory bowel disease, chronic kidney disease, heart failure) 2, 5
• Ongoing blood loss 5
• Second and third trimesters of pregnancy 5

Intravenous iron formulations that can replace iron deficits with 1 or 2 infusions are preferred over those that require more than 2 infusions. 2 All intravenous iron formulations have similar risks; true anaphylaxis is very rare (less than 1:250,000). 2, 4

Investigating Underlying Causes

Identify and address the source of iron depletion, including:

• Menstrual blood loss, especially menorrhagia (responsible for iron deficiency in 5-10% of menstruating women) 2, 1
• Gastrointestinal blood loss (accounts for 94% of cases in men and postmenopausal women) 4
• NSAID use causing occult gastrointestinal bleeding 2, 1
• Dietary insufficiency 1
• Malabsorption disorders (celiac disease, atrophic gastritis) 5

In men and postmenopausal women with iron deficiency, bidirectional endoscopy should be performed to evaluate for gastrointestinal blood loss. 4 Noninvasive testing for Helicobacter pylori infection and celiac disease is recommended as both are common causes. 4

Common Pitfalls to Avoid

• Do not recheck ferritin too early after starting treatment (wait 8-10 weeks minimum), as levels may be misleadingly elevated. 1, 3
• Do not supplement iron if ferritin is normal or elevated, as this provides no benefit and may be harmful. 1, 3
• Do not confuse this scenario with anemia of chronic disease, where ferritin may be normal or elevated due to inflammation despite functional iron deficiency. 1
• Failure to respond to oral iron is usually due to poor compliance, misdiagnosis, continued blood loss, or malabsorption. 2