What is the treatment for a patient with a ferritin level indicating severe iron deficiency?

Treatment of Severe Iron Deficiency (Ferritin 3 ng/mL)

A ferritin of 3 ng/mL represents severe absolute iron deficiency requiring immediate iron replacement therapy, with intravenous iron as first-line treatment in most clinical scenarios due to superior efficacy, faster response, and better tolerability compared to oral iron. 1

Diagnostic Confirmation and Workup

• Ferritin <30 ng/mL confirms absolute iron deficiency in patients without inflammatory conditions 1
• With a ferritin of 3 ng/mL, additional testing (transferrin saturation, complete blood count) should be obtained to assess severity and presence of anemia 1
• Investigate the underlying cause: evaluate for gastrointestinal blood loss (including H. pylori), menstrual losses in premenopausal women, malabsorption disorders (celiac disease), dietary inadequacy, or chronic inflammatory conditions 1
• In men and postmenopausal women, gastrointestinal evaluation is mandatory to exclude malignancy 1

Treatment Approach

Intravenous Iron (Preferred First-Line)

Intravenous iron should be strongly considered as first-line therapy for the following reasons and indications 1:

• Clinically active inflammatory bowel disease 1
• Hemoglobin <100 g/L (10 g/dL) 1
• Previous intolerance to oral iron 1
• Conditions with impaired absorption: celiac disease, post-bariatric surgery, atrophic gastritis 1
• Chronic inflammatory conditions: chronic kidney disease, heart failure, cancer 1, 2
• Pregnancy (second and third trimesters) 1, 2
• Ongoing blood loss 1, 2

Dosing: Calculate total iron deficit based on baseline hemoglobin and body weight using standard formulas 1

Common formulations: Ferric carboxymaltose has demonstrated efficacy in preventing anemia recurrence and is well-tolerated 1

Oral Iron (Alternative)

Oral iron may be used as first-line therapy only in patients with:

• Mild iron deficiency without anemia 1
• Clinically inactive disease (no inflammation) 1
• No previous intolerance to oral iron 1
• Hemoglobin ≥100 g/L 1

However, with a ferritin of 3 ng/mL, most patients will benefit more from IV iron given the severity of deficiency.

Oral iron dosing: Ferrous sulfate 325 mg daily (65 mg elemental iron) or alternate-day dosing to improve tolerability 1, 3, 4

Administration tips: Take on empty stomach for optimal absorption, or with meals if not tolerated; vitamin C 500 mg enhances absorption 1

Expected gastrointestinal side effects (nausea, constipation, abdominal pain) occur frequently and reduce compliance 1, 4

Monitoring and Maintenance

• Recheck complete blood count, ferritin, and inflammatory markers in 8-10 weeks to assess response 4
• Target ferritin levels: Maintain ferritin within normal range (>30-50 ng/mL in non-inflammatory conditions, >100 ng/mL in inflammatory conditions) 1
• Target hemoglobin: 120-130 g/L for women, 130-140 g/L for men 1

Maintenance Therapy

• Iron deficiency recurs frequently (>50% at 1 year), particularly in inflammatory bowel disease 1
• Proactive maintenance approach: Re-initiate IV iron when ferritin drops below 100 μg/L or hemoglobin falls below 120-130 g/L (gender-dependent) 1
• This proactive strategy reduces anemia recurrence rates and is cost-effective compared to "watch and wait" 1

Special Considerations

Inflammatory Conditions

• Ferritin is an acute-phase reactant and may be falsely elevated in inflammation 1, 5
• In inflammatory conditions, ferritin <100 μg/L or transferrin saturation <20% indicates iron deficiency even with "normal" ferritin 1, 5
• Check C-reactive protein to assess for inflammation 1

Chronic Kidney Disease

• Absolute iron deficiency defined as ferritin <100 ng/mL and TSAT <20% in CKD patients 1
• Functional iron deficiency can occur with adequate stores but insufficient availability for erythropoiesis 1
• Maintain TSAT ≥20% and ferritin ≥100 ng/mL in dialysis patients receiving erythropoietin 1

Common Pitfalls

• Do not delay treatment waiting for complete workup in symptomatic patients; iron replacement can begin while investigating etiology 1
• Do not use oral iron in active inflammatory conditions where absorption is compromised 1
• Do not assume ferritin >30 ng/mL excludes iron deficiency in inflammatory states 5
• Do not give IV iron test doses with newer formulations (ferric carboxymaltose, ferric gluconate) unless using iron dextran 1
• Avoid iron overload: Do not maintain TSAT >50% or ferritin >800 ng/mL chronically 1