What is the appropriate treatment for low ferritin in an adult with iron‑deficiency anemia?

Treatment of Low Ferritin in Adults with Iron Deficiency Anemia

Start with oral iron supplementation at one tablet daily (ferrous sulfate, fumarate, or gluconate containing 28-50 mg elemental iron), and if not tolerated, switch to alternate-day dosing or consider intravenous iron for specific clinical scenarios. 1, 2

Initial Treatment Approach

First-Line: Oral Iron Therapy

• Begin with ferrous sulfate 325 mg daily (or equivalent ferrous fumarate/gluconate) containing approximately 30-60 mg elemental iron 1, 2
• Alternate-day dosing (60 mg every other day) improves absorption and reduces gastrointestinal side effects compared to daily dosing, making it a preferred strategy when daily dosing causes intolerance 1, 2
• Monitor hemoglobin response within 2-4 weeks—expect a rise of ≥10 g/L within 2 weeks, which confirms iron deficiency even if initial iron studies were equivocal 1, 2
• Continue treatment until ferritin normalizes and for 3-6 months thereafter to replenish iron stores 1

Common Pitfall: Oral Iron Intolerance

Approximately 50% of patients experience decreased adherence due to gastrointestinal adverse effects (nausea, abdominal pain, constipation) 1, 2. When this occurs:

• Reduce to alternate-day dosing first before abandoning oral therapy 1, 2
• Consider lower-dose preparations (28-50 mg elemental iron) to minimize side effects while maintaining efficacy 3
• If intolerance persists, proceed directly to intravenous iron 1

Intravenous Iron: When to Use First-Line

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

Mandatory IV Iron Indications:

• Clinically active inflammatory bowel disease where oral iron may worsen inflammation 1
• Hemoglobin <100 g/L (10 g/dL) requiring rapid correction 1
• Previous intolerance to oral iron with documented gastrointestinal side effects 1
• Malabsorption conditions: celiac disease (present in 3-5% of IDA cases), post-bariatric surgery, atrophic gastritis 1, 4
• Heart failure with iron deficiency to improve exercise capacity, regardless of anemia status 5, 4
• Chronic kidney disease (non-dialysis dependent) with iron deficiency 5, 4
• Ongoing blood loss that cannot be immediately controlled 4
• Second and third trimesters of pregnancy when rapid repletion is needed 4

IV Iron Formulations and Safety:

• Ferric carboxymaltose (Injectafer) allows high-dose administration: typically 750-1000 mg per dose, given in 2 doses at least 7 days apart 5
• Hypersensitivity reactions with newer formulations are rare (<1%), but patients require monitoring during and for at least 30 minutes after infusion 5, 2
• Monitor for hypophosphatemia, especially with repeat treatments within 3 months—can cause bone pain, fractures, and muscle weakness 5

Investigation While Treating

Do not defer iron replacement therapy while awaiting investigations unless colonoscopy is imminent 1. However, concurrent investigation is essential:

Mandatory Workup in All Cases:

• Urinalysis or urine microscopy to exclude renal blood loss 1
• Celiac disease screening (tissue transglutaminase antibodies) found in 3-5% of IDA cases 1
• Helicobacter pylori testing as a common cause of iron malabsorption 1, 4

Endoscopic Investigation:

• In men and postmenopausal women: bidirectional endoscopy (gastroscopy and colonoscopy) is first-line to exclude gastrointestinal malignancy, as recurrent blood loss accounts for 94% of cases 1, 2
• In premenopausal women with heavy menstrual bleeding: treat the bleeding source and provide iron supplementation; endoscopy is not immediately required unless response is inadequate 2
• CT colonography is reasonable when colonoscopy is not feasible 1

Monitoring Treatment Response

Short-Term Monitoring (2-4 Weeks):

• Check hemoglobin at 2-4 weeks—expect ≥10 g/L rise with oral iron or ≥20 g/L with IV iron 1, 2
• If no response after 4 weeks of oral iron: switch to intravenous iron 1

Long-Term Monitoring:

• Repeat ferritin after 8-10 weeks to assess iron store repletion 3
• For recurrent or refractory IDA after negative bidirectional endoscopy: proceed to capsule endoscopy for small bowel evaluation 1
• Long-term intermittent oral iron may be necessary when the cause is irreversible (e.g., chronic menorrhagia, hereditary hemorrhagic telangiectasia) 1

Special Considerations by Ferritin Level

Ferritin <30 μg/L (without inflammation):

• Confirms absolute iron deficiency—treat with oral or IV iron based on clinical scenario 1, 6, 3

Ferritin 30-100 μg/L:

• Check transferrin saturation: if <20%, this indicates functional iron deficiency requiring treatment 1, 6

Ferritin <100 μg/L (with inflammation/CRP elevation):

• Diagnostic of iron deficiency in inflammatory conditions (IBD, CKD, heart failure)—use IV iron as first-line 1, 6

Critical Pitfall: Inflammation Masking Iron Deficiency

Ferritin is an acute-phase reactant that rises during inflammation, infection, or malignancy, potentially masking true iron deficiency 6. When CRP or ESR is elevated:

• Use ferritin <100 μg/L as the diagnostic threshold instead of <30 μg/L 1, 6
• Add transferrin saturation <20% as confirmatory evidence of inadequate iron delivery 1, 6

When to Consider Transfusion

Packed red cell transfusion is rarely needed but may be required for symptomatic severe anemia (e.g., angina, severe dyspnea, hemodynamic instability) 1. Iron replacement therapy is still mandatory post-transfusion to prevent recurrence 1.