What is the treatment for abnormal iron saturation levels?

Treatment of Abnormal Iron Saturation Levels

The treatment approach depends critically on whether you have iron deficiency (low saturation) or iron overload (high saturation), with oral iron as first-line for deficiency and phlebotomy for overload.

Low Iron Saturation (Iron Deficiency)

Initial Treatment Strategy

Start with oral iron supplementation using ferrous sulfate 200 mg once daily (containing 65 mg elemental iron), or consider alternate-day dosing if not tolerated. 1

• Ferrous sulfate, fumarate, or gluconate are all acceptable first-line options 1
• If standard daily dosing is not tolerated, reduce to one tablet every other day rather than discontinuing 1
• Alternate-day dosing increases fractional iron absorption by 35-45% compared to twice-daily dosing due to hepcidin regulation 1
• Take on an empty stomach for optimal absorption, or with a light meal if gastrointestinal side effects occur 1

Monitoring Response

Check hemoglobin response within the first 4 weeks of treatment, and continue therapy for approximately 3 months after hemoglobin normalizes to replenish iron stores. 1

• An adequate response is defined as hemoglobin increase ≥1 g/dL 1
• After iron stores are replenished, monitor blood counts every 6 months initially to detect recurrent deficiency 1
• Repeat iron studies 8-10 weeks after treatment initiation, not earlier, as ferritin levels may be falsely elevated immediately after IV iron 1

When to Use Intravenous Iron

Consider parenteral iron when oral iron is contraindicated, ineffective, not tolerated, or in specific clinical situations requiring rapid repletion. 1

Specific indications for IV iron include:

• Oral iron intolerance or gastrointestinal side effects 1, 2
• Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease) 1, 2
• Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer) 1, 2
• Ongoing blood loss that cannot be controlled 2
• Second and third trimesters of pregnancy 2
• Functional iron deficiency with transferrin saturation <20% despite adequate ferritin 1

Intravenous iron produces superior hemoglobin responses compared to oral iron in patients with chronic inflammatory conditions. 1

• In cancer-related anemia, IV iron achieved 73% hemoglobin response rate versus 45% with oral iron 1
• Ferric carboxymaltose can be administered as 1000 mg over 15 minutes as a single dose 1
• Iron sucrose and ferric gluconate are alternatives but may require multiple administrations 1
• Risk of serious reactions is very low (<1:250,000 administrations with recent formulations) but resuscitation facilities must be available 1

Specific Populations

For chronic kidney disease patients not on dialysis with hemoglobin <110 g/L, treat if serum ferritin <100 ng/mL or transferrin saturation <20%. 1

For hemodialysis patients, maintain serum ferritin >200 ng/mL and transferrin saturation >20% to optimize erythropoietin response and minimize ESA requirements. 1

For cancer and chemotherapy-induced anemia, perform iron studies before treatment to rule out absolute iron deficiency (transferrin saturation <15%, ferritin <30 ng/mL). 1

Common Pitfalls to Avoid

• Do not defer iron replacement while awaiting diagnostic investigations unless colonoscopy is imminent 1
• Avoid iron supplementation when ferritin is normal or elevated, as this is potentially harmful 1
• Do not use high-dose oral iron (>60 mg elemental iron) multiple times daily, as this stimulates hepcidin and reduces subsequent absorption 1
• Monitor renal function closely in pediatric patients, especially those receiving doses >25 mg/kg/day (deferasirox equivalent 17.5 mg/kg/day) when ferritin <1000 mcg/L 3

High Iron Saturation (Iron Overload)

Treatment Approach for Hemochromatosis

First-line treatment for iron overload is therapeutic phlebotomy, with an induction phase targeting serum ferritin of 50 μg/L, followed by maintenance to keep ferritin 50-100 μg/L. 1

• Perform phlebotomy weekly or fortnightly during induction until iron stores are depleted 1
• Erythrocytapheresis is a cost-effective alternative requiring fewer interventions 1
• Target ferritin of 50 μg/L during induction, but not lower to avoid iron deficiency 1

Iron Chelation Therapy

If phlebotomy is not possible, consider iron chelation therapy with deferasirox after careful risk-benefit assessment, but avoid in advanced liver disease. 1, 3

• Deferasirox is the most studied oral chelator but is not approved by European Medicines Agency for hemochromatosis 1
• Associated with gastrointestinal side effects and impaired kidney function 1
• Contraindicated in patients with eGFR <40 mL/min/1.73 m² 3
• For transfusion-related iron overload, deferasirox doses range from 5-30 mg/kg/day based on baseline liver iron concentration 3

Dietary Modifications

Dietary modifications should not substitute for iron removal therapy but can be adjunctive. 1

• Avoid iron supplementation and iron-fortified foods 1
• Avoid supplemental vitamin C, especially before iron depletion 1
• Limit red meat consumption 1
• Restrict or abstain from alcohol, particularly with liver abnormalities or cirrhosis 1
• Consume citrus fruits and juices in moderation, not with other foods 1
• Avoid handling raw shellfish and seawater exposure due to infection risk 1