What are the treatment options for abnormal ferritin levels indicating iron deficiency or overload?

Treatment of Abnormal Ferritin Levels

For iron deficiency with low ferritin, oral iron supplementation at 100-200 mg/day (or alternate-day dosing) is first-line therapy, while intravenous iron is reserved for specific indications including malabsorption, intolerance, ongoing blood loss, chronic inflammatory conditions, or pregnancy. 1

Iron Deficiency Treatment Algorithm

When to Treat Iron Deficiency

Iron deficiency should be treated when associated with anemia and/or low ferritin levels. 1 Iron supplementation when ferritin is normal or high is not recommended and potentially harmful. 1

Diagnostic Thresholds Guiding Treatment

• Ferritin <15 μg/L: Absolute iron deficiency confirmed (99% specificity); initiate treatment immediately 2, 3
• Ferritin 15-30 μg/L: Low iron stores; treatment warranted 2
• Ferritin 30-100 μg/L with inflammation: Mixed picture requiring inflammatory marker assessment (CRP/ESR) 2
• In inflammatory conditions (CKD, IBD, heart failure): Use ferritin <100 ng/mL as threshold 2, 4

Oral Iron Therapy (First-Line)

Typical dosing is 100-200 mg/day of elemental iron in divided doses. 1 Recent evidence supports alternate-day dosing for better absorption and fewer adverse effects. 1

• Ferrous sulfate 325 mg daily or on alternate days is the most cost-effective first-line option 4, 5
• Pediatric dosing: 3-6 mg/kg of elemental iron per day 6
• Common side effects: Constipation, diarrhea, nausea (approximately 50% of patients experience reduced adherence due to adverse effects) 1, 3

Dietary counseling is important: Integrate heme and free iron regularly; avoid inhibitors of iron uptake 1

Intravenous Iron Therapy (Specific Indications)

IV iron is indicated when: 1, 4, 3

• Oral iron fails to reach therapeutic goals
• Rapid supplementation needed (e.g., before elective surgery)
• Repeated failure of oral therapy
• Malabsorption conditions (celiac disease, post-bariatric surgery)
• Oral iron intolerance
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
• Ongoing blood loss
• Second and third trimesters of pregnancy 4, 3

Available IV formulations: 1

• Iron sucrose and ferric gluconate: Widely used but may require multiple administrations
• Ferric carboxymaltose: Best studied; infused over 15 minutes, allows rapid administration of large single doses 1
• Other options: Ferumoxytol, isomaltoside, low molecular weight iron dextran 1

Critical safety consideration: Reactions during IV iron infusions are very infrequent (<1:250,000 administrations with recent formulations) but may be life-threatening. 1 Risk is highest with high molecular weight iron dextran. 1 For iron dextran, a one-time test dose of 25 mg IV (adults) or 10-15 mg (pediatrics) should be given before routine dosing. 1

In critically ill patients with inflammation: After hepcidin-confirmed deficiency, 1 g elemental iron as ferric carboxymaltose was associated with reduced hospital length of stay and 90-day mortality. 1

Monitoring Treatment Response

Repeat blood tests after 8-10 weeks, not earlier after iron infusion, as ferritin levels are falsely high immediately post-infusion. 1 For oral iron therapy, evaluate response in 2-4 weeks. 3

Patients who cannot tolerate oral iron or lack adequate response should receive intravenous iron. 3

Iron Overload Treatment

Diagnostic Thresholds for Overload

• TSAT >50%: No physiologic rationale for maintaining levels above this 1
• Ferritin 300-800 ng/mL: Common in dialysis patients without evidence of adverse iron-mediated effects 1
• Ferritin >500 ng/mL: Upper limit for hemodialysis patients per KDIGO 2012 1
• TSAT ≥80%: Seen in transfusional hemosiderosis 1

Treatment of Iron Overload

Deferoxamine (FDA-approved chelation therapy) is indicated for: 7

• Acute iron intoxication (as adjunct to standard measures)
• Chronic iron overload due to transfusion-dependent anemias
• Long-term therapy slows hepatic iron accumulation and retards/eliminates hepatic fibrosis progression 7

Important caveat: Deferoxamine is not indicated for primary hemochromatosis—phlebotomy is the method of choice. 7 Iron mobilization is relatively poor in patients under age 3 years with little iron overload; should not be given unless significant iron mobilization (≥1 mg iron/day) can be demonstrated. 7

In hemodialysis patients: Iron overload can be avoided by temporarily withholding IV iron when TSAT or ferritin levels become too high. 1 Monitor TSAT and ferritin at least every 3 months to optimize erythropoiesis by adjusting IV iron dosing. 1

Critical Pitfall: Avoiding Iatrogenic Overload

Recent guidelines advocating higher ferritin targets (>250-500 μg/L) in dialysis patients have contributed to excessive IV iron use. 1 In the US, median ferritin rose from 556 to 650 μg/L between 2010-2011, with 34% of patients exceeding 800 μg/L. 1 This trend raises concerns about long-term safety despite short-term tolerability in trials. 1

Special Populations

Chronic Kidney Disease

• Absolute iron deficiency: Ferritin <100 ng/mL and TSAT <20% 2
• Functional iron deficiency: Normal/elevated ferritin but TSAT <20% 2
• Hepcidin is a more reliable indicator than transferrin saturation in critically ill patients with variable inflammation 1

Pregnancy

• Iron deficiency affects up to 84% of pregnant women in third trimester 4
• IV iron is specifically indicated during second and third trimesters 4, 3

Inflammatory Conditions

Ferritin is an acute-phase reactant; inflammation falsely elevates levels, potentially masking iron deficiency. 1, 2, 8 In these patients, ferritin thresholds shift upward to <100 μg/L for diagnosing deficiency. 2