What are the treatment options for high ferritin levels?

Treatment Options for High Ferritin Levels

The treatment of high ferritin levels should be determined by the underlying cause, with phlebotomy being the first-line treatment for hereditary hemochromatosis and iron chelation therapy for transfusional iron overload. 1

Diagnostic Approach to High Ferritin

Before initiating treatment, it's crucial to determine whether high ferritin represents true iron overload or is secondary to inflammation:

1. Assess transferrin saturation (TSAT):

   • TSAT >45-50% suggests true iron overload 1, 2
   • TSAT <20% with high ferritin suggests inflammation 2

2. Consider additional testing:

   • HFE gene testing for hereditary hemochromatosis
   • MRI or liver biopsy to confirm hepatic iron overload in non-HFE genotypes 1
   • Inflammatory markers (CRP, ESR) to identify inflammatory conditions

Treatment Options Based on Etiology

1. Hereditary Hemochromatosis

• Therapeutic phlebotomy (first-line treatment):

  • Initial frequency: Weekly removal of 500 mL blood 1
  • Check hemoglobin/hematocrit before each phlebotomy
  • Monitor serum ferritin every 10-12 phlebotomies
  • Induction phase target: Ferritin 50-100 μg/L 1
  • Maintenance phase: Continue phlebotomy at intervals to maintain ferritin 50-100 μg/L 1

• Dietary modifications:

  • Avoid vitamin C supplements (increases iron absorption) 1
  • Avoid iron supplements and iron-fortified foods 2
  • No need for strict dietary iron restrictions (minimal impact compared to phlebotomy) 1

2. Transfusional Iron Overload

• Iron chelation therapy (indicated when):

  • Serum ferritin >1000 ng/mL 1, 3
  • Transfusion need ≥2 units/month for >1 year 1
  • Evidence of organ dysfunction 1

• Chelation options:

  • Deferasirox (oral): Starting dose 14 mg/kg/day, adjust based on ferritin levels 3
  • Deferoxamine: 20-40 mg/kg/day 1
  • Monitor ferritin levels monthly and adjust dose every 3-6 months 3
  • Target ferritin: <1000 ng/mL, interrupt therapy if <500 ng/mL 3

3. Inflammatory Conditions with High Ferritin

• Treat the underlying inflammatory condition 2
• Consider IV iron if TSAT <20% despite elevated ferritin (functional iron deficiency) 2
• Do not initiate phlebotomy or chelation if high ferritin is due to inflammation without iron overload 2

4. Secondary Iron Overload in Liver Disease

• Address underlying liver disease (alcohol cessation, weight loss for NAFLD) 2
• Consider phlebotomy in select cases:
  • Beneficial in porphyria cutanea tarda 1
  • May improve insulin resistance parameters in NAFLD 1
  • Limited evidence for benefit in chronic hepatitis C 1

Monitoring Recommendations

• Frequency:

  • Monitor serum ferritin every 3 months initially 1, 2
  • More frequent monitoring as ferritin approaches target range 2
  • Check hemoglobin/hematocrit before each phlebotomy 1

• Additional monitoring:

  • Liver function tests every 3 months 2
  • Regular assessment of end-organ damage (liver, heart, joints) 1
  • Patients with advanced fibrosis should be screened for hepatocellular carcinoma 1

Clinical Pitfalls to Avoid

• Don't assume all high ferritin represents iron overload - 90% of elevated ferritin cases are due to non-iron overload conditions 4
• Don't initiate phlebotomy based solely on high ferritin without confirming iron overload (elevated TSAT, MRI or biopsy confirmation) 2
• Don't overlook malignancy as a potential cause of markedly elevated ferritin 5
• Don't set arbitrary ferritin cutoffs without considering clinical context 2
• Don't use phlebotomy in patients with anemia (Hb <11 g/dL) 2

By following this approach, clinicians can appropriately manage patients with high ferritin levels, ensuring treatment is directed at the underlying cause rather than the laboratory value alone.