How are elevated iron levels treated?

Treatment of Elevated Iron Levels

The primary treatment for elevated iron levels is therapeutic phlebotomy, which should be initiated when serum ferritin levels reach 1,000 ng/mL or when patients require regular blood transfusions (≥2 units/month for >1 year). 1, 2

Diagnostic Evaluation Before Treatment

Before initiating treatment, confirm iron overload with:

• Complete iron studies (serum ferritin, transferrin saturation, serum iron, TIBC)
• Genetic testing for HFE mutations (C282Y, H63D) if hereditary hemochromatosis is suspected
• Assessment of organ function (liver enzymes, cardiac function, glucose levels)
• Consider MRI for quantitative iron assessment in liver/heart if available

Treatment Algorithm Based on Etiology

1. Primary Hemochromatosis

• First-line: Therapeutic phlebotomy
  • Initial phase: Remove one unit of blood (450-500 mL) weekly as tolerated
  • Target ferritin level: 50-100 μg/L 1
  • Monitor hemoglobin before each phlebotomy
  • Check ferritin after every 10-12 phlebotomies initially, then more frequently as target approaches

2. Secondary Iron Overload (Transfusion-Dependent)

• First-line: Iron chelation therapy
  • Options include:
    • Deferasirox (oral): Starting dose 14 mg/kg/day, adjust based on response 3
    • Deferoxamine (subcutaneous/intravenous): 40 mg/kg/day for 8-12 hours, 5-7 nights weekly 1
  • Monitor ferritin levels every 3 months (monthly if possible) 1
  • Continue chelation as long as transfusion therapy is needed 1

3. Secondary Iron Overload (Non-Transfusion Dependent)

• Phlebotomy for patients who can tolerate it (adequate hemoglobin)
• Iron chelation for patients who cannot tolerate phlebotomy

Special Populations

Myelodysplastic Syndrome (MDS) Patients

Iron chelation therapy should be considered for:

• Patients with ferritin levels >1,000 ng/mL
• Low-risk MDS (IPSS low or intermediate-1)
• Life expectancy of at least one year
• Transfusion-dependent patients requiring ≥2 units/month for >1 year 1

Patients Undergoing Stem Cell Transplantation

• Iron chelation prior to transplant for patients with ferritin >1,000 ng/mL
• Post-transplant: Phlebotomy is preferred for iron removal once stable engraftment is achieved (>1 year post-SCT) 1

Cardiac Iron Overload

• More aggressive chelation may be needed
• Cardiac T2* MRI is the best predictor of cardiac risk (high risk if T2* <10 ms) 1
• Consider combination chelation therapy in severe cases

Monitoring During Treatment

• Serum ferritin: Every 3 months (monthly if possible)
• Liver function tests: Regular monitoring
• Cardiac function: Regular assessment in transfusion-dependent patients
• For patients on chelation therapy:
  • Renal function (especially with deferasirox)
  • Auditory and visual testing (with deferoxamine)
  • Monitor for side effects specific to each chelator

Common Pitfalls to Avoid

1. Misinterpreting elevated ferritin: Ferritin can be elevated in inflammatory conditions without true iron overload; confirm with transferrin saturation and other tests 2

2. Overtreatment: Never reduce ferritin below 50 μg/L to avoid iron deficiency 1, 2

3. Vitamin C supplementation: Patients should avoid vitamin C supplements >500 mg/day during treatment as it can accelerate iron mobilization and increase toxicity 1, 2

4. Neglecting organ monitoring: Regular assessment of liver, heart, and endocrine function is essential

5. Discontinuing treatment prematurely: Iron overload requires long-term management; maintenance therapy is often needed even after target ferritin is achieved 1

6. Ignoring dietary factors: While diet alone cannot treat iron overload, patients should limit iron-rich foods, alcohol, and raw shellfish 2

The treatment of elevated iron levels requires a systematic approach based on the etiology and severity of iron overload, with careful monitoring to prevent complications and improve long-term outcomes.