What is the approach to managing iron overload?

Management of Iron Overload

The primary approach to managing iron overload should be regular phlebotomies until iron stores are depleted, followed by lifelong maintenance therapy with the frequency determined by serum ferritin levels. 1

Diagnosis of Iron Overload

Laboratory Assessment

• Comprehensive iron studies should include:
  • Serum iron
  • Transferrin
  • Transferrin saturation (>45% suggests hereditary hemochromatosis)
  • Serum ferritin
  • C-reactive protein (to assess inflammation)
  • Hepcidin levels
  • Red blood cell morphology 1

Diagnostic Thresholds

• Definitive iron overload: Ferritin >300 μg/L in the absence of inflammation 2
• In inflammatory conditions: Higher ferritin levels may be present due to ferritin acting as an acute-phase reactant 2

Treatment Approach Based on Etiology

Primary Hemochromatosis (Hereditary)

1. Initial Phlebotomy Phase:

   • Remove 450-500 mL of blood weekly
   • Monitor hematocrit before each phlebotomy (allow no more than 20% drop from prior level)
   • Check serum ferritin every 10-12 phlebotomies
   • Continue until serum ferritin falls below 50 μg/L 2

2. Maintenance Phase:

   • Continue phlebotomy at intervals to maintain serum ferritin between 25-50 μg/L
   • Typically requires phlebotomy every 1-4 months 2

Secondary Iron Overload

For Patients Who Can Tolerate Phlebotomy

• Use similar regimen as for hereditary hemochromatosis 1
• Particularly effective in:
  • African iron overload
  • Porphyria cutanea tarda 1

For Patients With Anemia or Who Cannot Tolerate Phlebotomy

• Iron Chelation Therapy:

  1. Deferasirox (Oral):

     • Starting dose: 14 mg/kg/day
     • Maximum dose: 28 mg/kg/day
     • Take on an empty stomach or with a light meal
     • Avoid aluminum-containing antacids 3
     • Dose adjustments:
       • Reduce starting dose by 50% in moderate hepatic impairment
       • Avoid in severe hepatic impairment or eGFR <40 mL/min/1.73 m² 3

  2. Deferoxamine (Parenteral):

     • Subcutaneous infusion: 40 mg/kg/day over 8-12 hours, 5-7 days/week
     • Intravenous administration: 40-50 mg/kg/day over 8-12 hours at a rate up to 15 mg/kg/hour
     • Maximum dose: 60 mg/kg/day 4
     • Contraindicated in severe renal disease or anuria 4

Monitoring During Treatment

During Phlebotomy

• Hemoglobin/hematocrit: Before each phlebotomy session
• Serum ferritin: Every 3-4 months during maintenance phase
• Target for maintenance therapy: Serum ferritin ≤50 μg/L 2

During Chelation Therapy

• Serum ferritin: Every 3 months
• Renal function: Monthly (weekly for first month in high-risk patients)
• Liver function tests: Every 2 weeks during first month, then monthly
• Auditory and visual testing: Periodic assessments for patients on long-term deferoxamine 4
• Goal: Decrease serum ferritin to <1000 ng/mL and maintain negative iron balance 2

Special Considerations

Organ-Specific Monitoring

• Cardiac Assessment: Regular cardiac evaluation for patients with significant iron overload to detect early cardiomyopathy 1, 5
• Hepatic Surveillance: Patients with cirrhosis due to iron overload should undergo regular screening for hepatocellular carcinoma 1
• Endocrine Evaluation: Screen for diabetes and other endocrine disorders 2

Adjunctive Measures

• Dietary Modifications:
  • Avoid iron supplements and iron-fortified foods
  • Limit red meat consumption
  • Restrict alcohol intake 2
• Vitamin C Management:
  • Avoid vitamin C supplements during initial treatment phase
  • After one month of regular chelation/phlebotomy, may add vitamin C in doses up to 200 mg/day for adults (divided doses)
  • For children: 50 mg daily for those under 10 years, 100 mg daily for older children 4

Complications and Pitfalls

1. Delayed Treatment: Early diagnosis and treatment are critical as cardiac dysfunction is reversible if therapy is introduced before overt heart failure 5

2. Vitamin C Caution: Excessive vitamin C can increase iron absorption and mobilization, potentially worsening iron toxicity 4

3. Monitoring Gaps: Failure to regularly monitor organ function can lead to missed detection of toxicity from either iron overload or treatment 4

4. Chelator Side Effects: Watch for:

   • Deferasirox: Renal impairment, hepatotoxicity
   • Deferoxamine: Auditory and ocular toxicity, especially with prolonged treatment, higher doses, or low ferritin levels 4

5. Post-Transplantation: In patients who undergo liver transplantation, iron overload may persist and require continued management 1