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

Management of Low Ferritin (Iron Deficiency)

Oral iron supplementation at 100-200 mg elemental iron daily (or alternate-day dosing) is the first-line treatment for iron deficiency with low ferritin, provided the patient has no anemia or only mild anemia, clinically inactive disease, and no prior intolerance to oral iron. 1

When to Treat

• Iron deficiency should be treated when associated with anemia and/or low ferritin levels 1
• Iron supplementation in the presence of normal or high ferritin values is not recommended and is potentially harmful 1
• Treatment goals include normalizing both hemoglobin levels and iron stores, not just correcting anemia 1, 2

Diagnostic Thresholds for Iron Deficiency

Without Inflammation

• Ferritin <30 μg/L indicates iron deficiency in adults without inflammatory conditions 1
• In the presence of inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 1

With Inflammation

• Ferritin >100 μg/L with transferrin saturation <20% suggests anemia of chronic disease 1
• Ferritin between 30-100 μg/L suggests a combination of true iron deficiency and anemia of chronic disease 1

First-Line Treatment: Oral Iron

Dosing

• Typical dose: 100-200 mg elemental iron daily in divided doses 1
• Ferrous sulfate 324 mg tablets contain 65 mg elemental iron 3
• Recent evidence supports alternate-day dosing for better absorption and fewer adverse effects 1

Who Should Receive Oral Iron First-Line

• Patients with mild anemia (hemoglobin >100 g/L or >10 g/dL) 1, 2
• Clinically inactive disease 1
• No previous intolerance to oral iron 1

Common Pitfalls with Oral Iron

• Gastrointestinal side effects (constipation, diarrhea, nausea) are common and reduce compliance 1
• Avoid oral iron in patients with active inflammation, as absorption is compromised 2
• Approximately 50% of patients have decreased adherence due to adverse effects 4

When to Use Intravenous Iron as First-Line

IV iron should be considered first-line in the following situations: 1, 2

• Clinically active inflammatory disease (especially IBD) 1
• Hemoglobin <100 g/L (<10 g/dL) 1, 2
• Previous intolerance to oral iron 1
• Patients requiring rapid iron replacement (e.g., before elective surgery) 1
• Patients not reaching therapeutic goals with oral supplementation 1
• Patients requiring erythropoiesis-stimulating agents 1

IV Iron Dosing

For single-dose IV iron replacement: 1

Hemoglobin Level	Body Weight <70 kg	Body Weight ≥70 kg
100-120 g/L (women) or 100-130 g/L (men)	1000 mg	1500 mg
70-100 g/L	1500 mg	2000 mg

1, 2

IV Iron Formulations

• Ferric carboxymaltose is the best-studied formulation, infused over 15 minutes 1
• Iron sucrose and ferric gluconate are widely used but may require multiple administrations 1
• Avoid high molecular weight iron dextran due to highest risk of reactions 1
• Hypersensitivity reactions are very infrequent (<1:250,000 administrations with recent formulations) but may be life-threatening 1
• Do not use iron dextran preparations without test dosing due to risk of serious anaphylactic reactions 2

Evidence for IV Iron in Critical Illness

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

Monitoring Treatment Response

Timing of Follow-Up

• Repeat blood tests after 8-10 weeks, not earlier after IV iron infusion as ferritin levels are falsely elevated 1
• An acceptable response is ≥2 g/dL hemoglobin increase within 4 weeks 2
• Patients taking oral iron should be evaluated for response in 2-4 weeks 4

Re-Treatment Criteria

• Re-treatment with IV iron should be initiated when serum ferritin drops below 100 μg/L or hemoglobin falls below 120 g/L (women) or 130 g/L (men) 1, 2

Adjunctive Dietary Measures

• Dietary advice is important after excluding medical causes of deficiency 1
• Integrate heme and free iron regularly into the diet and avoid inhibitors of iron uptake 1
• Dietary modifications should not substitute for iron removal therapy 1

Special Populations

Inflammatory Bowel Disease

• IV iron is more effective, shows faster response, and is better tolerated than oral iron in IBD patients 1
• All IBD patients should be assessed for low ferritin levels, reduced transferrin saturation, and anemia 1
• Monitoring should occur every 6-12 months in remission or mild disease, and every 3 months in active disease 1

Patients Who Fail Oral Iron

• Patients who cannot tolerate oral iron or do not have adequate response should receive IV iron 4
• IV iron is indicated for poor absorption (celiac disease, post-bariatric surgery), chronic inflammatory conditions (CKD, heart failure, IBD, cancer), and ongoing blood loss 5