What is the treatment for elevated ferritin levels?

Treatment for Elevated Ferritin

Therapeutic phlebotomy is the primary treatment for elevated ferritin levels associated with iron overload, with a target ferritin level of 50-100 μg/L. 1

Diagnostic Approach Before Treatment

Before initiating treatment, it's essential to determine the cause of elevated ferritin:

1. Initial evaluation: Measure both transferrin saturation (TS) and ferritin

   • If TS ≥45% and/or elevated ferritin: Consider hereditary hemochromatosis (HH)
   • If either is abnormal: Perform HFE mutation analysis 1

2. Common causes of elevated ferritin:

   • Iron overload conditions (10% of cases):

     • Hereditary hemochromatosis (HH)
     • Transfusional iron overload
     • Ferroportin disease

   • Non-iron overload conditions (90% of cases) 2:

     • Inflammatory conditions (infections, rheumatologic disorders)
     • Malignancy
     • Liver disease
     • Metabolic syndrome/obesity/diabetes
     • Alcohol consumption

Treatment Algorithm Based on Cause

1. Hereditary Hemochromatosis (HH)

Treatment protocol:

• Weekly phlebotomy (removal of 500 mL blood) 1
• Check hematocrit/hemoglobin prior to each phlebotomy
• Allow hematocrit/hemoglobin to fall by no more than 20% of prior level
• Check serum ferritin level every 10-12 phlebotomies
• Initial phase: Continue frequent phlebotomy until serum ferritin reaches 50-100 μg/L
• Maintenance phase: Continue phlebotomy at intervals to keep ferritin between 50-100 μg/L 1

2. Transfusional Iron Overload

Treatment options:

• Phlebotomy: If tolerated (patients without anemia)
• Iron chelation therapy: For patients with anemia or who cannot tolerate phlebotomy
  • Deferasirox: Initial dose 14 mg/kg/day orally
    • Monitor serum ferritin monthly
    • Adjust dose every 3-6 months based on ferritin trends
    • If ferritin falls below 1000 μg/L at 2 consecutive visits, consider dose reduction
    • If ferritin falls below 500 μg/L, interrupt therapy 3

3. Non-Iron Overload Conditions

• Treat the underlying cause:
  • Inflammatory conditions: Treat underlying inflammation
  • Metabolic syndrome: Weight loss, glycemic control
  • Alcohol-related: Alcohol cessation
  • Liver disease: Manage underlying liver condition

Special Considerations

Ferritin >1000 μg/L

• Referral to specialist (gastroenterologist, hematologist, or physician with interest in iron overload) is recommended 2
• Consider liver biopsy if:
  • Ferritin >1000 μg/L with elevated liver enzymes and platelet count <200 (80% predictive of cirrhosis in C282Y homozygotes) 1

Monitoring During Treatment

• Monthly monitoring of:
  • Serum ferritin
  • Complete blood count
  • Liver function
  • Renal function 1, 3

Precautions During Treatment

• Avoid vitamin C supplements in iron-loaded patients, particularly during phlebotomy 1
• Avoid raw shellfish in patients with HH (risk of Vibrio vulnificus infection) 1
• No dietary adjustments necessary during treatment 1

Treatment Considerations for Specific Populations

Patients with Elevated Ferritin and Normal Transferrin Saturation

• May indicate non-iron overload condition
• Investigate for inflammatory conditions, malignancy, liver disease, etc.
• Treatment should target underlying cause rather than iron removal 1, 4

Patients with Elevated Ferritin in Chronic Kidney Disease

• Intravenous iron may be considered even with ferritin levels up to 1200 ng/ml if transferrin saturation is <25% 1
• Monitor closely for adverse events

When to Refer to Specialist

• Ferritin >1000 μg/L
• Unclear cause of hyperferritinemia
• Suspected hereditary hemochromatosis
• Evidence of end-organ damage
• Need for iron chelation therapy

Remember that markedly elevated ferritin (>2000 μg/L) is most commonly associated with malignancy and infectious diseases, rather than primary iron overload conditions 5, 6. MRI assessment of liver iron concentration may be helpful in distinguishing true iron overload from other causes of hyperferritinemia 7.