What is the treatment for low ferritin (iron deficiency)?

Treatment of Low Ferritin (Iron Deficiency)

Iron deficiency should be treated when associated with low ferritin levels and/or anemia, using oral iron as first-line therapy (100-200 mg elemental iron daily or alternate-day dosing) for most patients, with intravenous iron reserved for specific clinical scenarios including oral intolerance, malabsorption, active inflammation, severe anemia (hemoglobin <100 g/L), or need for rapid repletion. 1

Diagnostic Thresholds and When to Treat

• Ferritin cutoff values vary by clinical context: The most recent AGA guideline recommends a ferritin threshold of 45 μg/L for diagnosing iron deficiency in anemic patients, though this may miss cases in inflammatory conditions where ferritin can be falsely elevated 1

• In inflammatory conditions (IBD, CKD, heart failure), iron deficiency may exist with ferritin levels between 45-100 μg/L; confirmatory testing with transferrin saturation (<20%), soluble transferrin receptor, or reticulocyte hemoglobin may be needed 1

• For healthy adults >15 years: A ferritin cutoff of 30 μg/L is appropriate for diagnosis 2

• Emerging evidence suggests the physiologic ferritin "cutoff" may actually be 50 ng/mL, as 30-50% of healthy women have no marrow iron stores despite ferritin levels within current laboratory reference ranges 3

First-Line Treatment: Oral Iron Supplementation

Dosing and Formulations

• Standard dosing: 100-200 mg elemental iron daily in divided doses 1

• Alternate-day dosing shows better iron absorption and possibly fewer adverse effects compared to daily dosing 1

• Ferrous salts (ferrous sulfate, ferrous fumarate, ferrous gluconate) are reasonable first-choice options as they are least expensive, with no substantial evidence that any one oral formulation is superior 1

• Typical ferrous sulfate dose: 325 mg daily or on alternate days 4

• Preparations with 28-50 mg elemental iron may improve compliance by reducing gastrointestinal side effects 2

Optimizing Absorption

• Take on empty stomach when possible for better absorption; some patients tolerate taking with meals better 1

• Co-administer with vitamin C (500 mg) to enhance absorption, especially with non-heme iron sources 1

• Avoid tea and coffee around meal times as they impair iron absorption 1

Common Side Effects

• Gastrointestinal side effects are common: constipation, diarrhea, nausea 1

• These side effects reduce compliance and may necessitate switching to intravenous therapy 1

Intravenous Iron Therapy: Indications and Administration

When to Use IV Iron

IV iron should be considered as first-line treatment in the following scenarios: 1

• Active inflammatory bowel disease with compromised absorption 1
• Previous intolerance to oral iron 1
• Hemoglobin below 100 g/L 1
• Patients requiring erythropoiesis-stimulating agents 1
• Failure to reach therapeutic goals with oral supplementation 1
• Need for rapid supplementation (e.g., before elective surgery in patient blood management) 1
• Chronic kidney disease (especially hemodialysis patients) 1
• Heart failure with iron deficiency 4, 5
• Second and third trimesters of pregnancy 4
• Ongoing blood loss 4
• Malabsorption conditions (celiac disease, post-bariatric surgery) 1, 4

IV Iron Formulations and Dosing

• Modern carbohydrate-bound formulations (ferric carboxymaltose, ferumoxytol, iron isomaltoside, low molecular weight iron dextran) allow rapid administration of large single doses 1

• Avoid high molecular weight iron dextran due to highest risk of reactions 1

• Ferric carboxymaltose: 1 g elemental iron as a single dose over 15 minutes is well-studied and recommended 1

• In critically ill anemic patients with iron deficiency confirmed by low hepcidin, 1 g iron as carbohydrate product was associated with reduced hospital length of stay and 90-day mortality 1

• For hemodialysis patients: 100 mg undiluted as slow IV injection over 2-5 minutes per dialysis session, usual total course 1000 mg 6

• For non-dialysis CKD: 200 mg on 5 occasions over 14 days, or two 500 mg infusions on Day 1 and Day 14 6

Safety Considerations

• Infusion reactions are very infrequent (<1:250,000 administrations with recent formulations) but may be life-threatening 1

• Monitor serum ferritin and preferably keep below 500 μg/L to avoid iron overload toxicity, especially in children and adolescents 1

• Do not supplement iron when ferritin is normal or high, as this is potentially harmful 1, 2

• Potential risks of high-dose IV iron include allergic reactions, hypophosphatemia/osteomalacia, iron overload, and vascular leakage 5

Population-Specific Recommendations

Inflammatory Bowel Disease

• Oral iron for mild anemia with clinically inactive disease and no previous intolerance 1

• IV iron for clinically active IBD, previous oral intolerance, hemoglobin <100 g/L 1

• Re-treatment with IV iron when ferritin drops below 100 μg/L or hemoglobin below 12-13 g/dL (gender-dependent) 1

Chronic Kidney Disease

• Hemodialysis patients receiving ESAs: Target ferritin >200 ng/mL and transferrin saturation >20% for optimal anemia correction at lower ESA doses 1

• Consider IV iron even with elevated ferritin (500-1200 ng/mL) if transferrin saturation <25% and high ESA requirements 1

Pediatric Patients (≥2 years)

• Iron maintenance in hemodialysis: 0.5 mg/kg (max 100 mg) every 2 weeks for 12 weeks 6

• Non-dialysis or peritoneal dialysis on erythropoietin: 0.5 mg/kg (max 100 mg) every 4 weeks for 12 weeks 6

Monitoring Treatment Response

• Repeat blood tests after 8-10 weeks of oral iron therapy 1, 2

• Do not test earlier after IV iron infusion as ferritin levels are falsely elevated 1

• Basic tests include: hemoglobin, hematocrit, mean cellular volume, mean cellular hemoglobin, ferritin 2

• For patients with repeatedly low ferritin: Intermittent oral supplementation to preserve stores with follow-up testing every 6-12 months 2

Critical Pitfalls to Avoid

• Do not rely solely on ferritin in inflammatory conditions as it is an acute phase reactant and can be falsely normal or elevated despite true iron deficiency 1

• Exclude acute phase reaction by checking C-reactive protein when interpreting ferritin 2

• Do not provide long-term daily oral or IV iron when ferritin is normal or high—this is potentially harmful 1, 2

• Address underlying causes: Evaluate for gastrointestinal bleeding, menstrual losses, malabsorption (celiac disease, H. pylori, atrophic gastritis), dietary inadequacy 1, 4

• Dietary counseling is essential: Integrate heme iron (meat) regularly, use absorption enhancers (vitamin C), avoid inhibitors (tea, coffee) 1