What are the treatment options for a patient with hyperferritinemia (elevated ferritin level)?

Treatment Options for Hyperferritinemia

The primary treatment for hyperferritinemia depends on the underlying cause, with therapeutic phlebotomy being the first-line treatment for iron overload when ferritin levels exceed 1,000 ng/mL, while chelation therapy is reserved for specific conditions where phlebotomy is contraindicated. 1

Diagnostic Approach to Elevated Ferritin

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

1. Complete Iron Studies:

   • Serum iron, TIBC, transferrin saturation, and ferritin
   • Transferrin saturation >50% suggests iron overload

2. Additional Testing:

   • Complete blood count with reticulocyte count
   • Liver function tests (AST, ALT, bilirubin)
   • Inflammatory markers (CRP)
   • Specialized tests: reticulocyte hemoglobin content (CHr), soluble transferrin receptor (sTfR)

3. Common Causes of Hyperferritinemia 2, 3:

   • Iron overload syndromes
   • Inflammatory conditions
   • Malignancies
   • Liver disease
   • Infections
   • Renal failure
   • Metabolic syndrome

Treatment Algorithm Based on Cause and Ferritin Level

1. Iron Overload Conditions (Ferritin >1,000 ng/mL)

Primary Treatment: Therapeutic Phlebotomy 1

• Protocol: Weekly phlebotomy (400-500 mL, containing 200-250 mg of iron)
• Target: Ferritin level of 50-100 μg/L
• Monitoring: Monthly during induction phase, every 6 months during maintenance

Chelation Therapy (when phlebotomy is contraindicated) 4, 5

• Indications:

  • Transfusion-dependent patients requiring ≥2 units/month for >1 year
  • Patients with ferritin levels >1,000 ng/mL
  • Patients with myelodysplastic syndromes (MDS) with low-risk disease
  • Candidates for allogeneic stem cell transplant
  • Need to preserve organ function

• Medication Options:

  1. Deferoxamine 5

     • Dosing:
       • Subcutaneous: 20-60 mg/kg/day (average)
       • IV: 40-50 mg/kg/day over 8-12 hours (adults)
       • IM: 500-1,000 mg/day
     • Ferritin-based dosing:
       • Ferritin <2,000 ng/mL: 25 mg/kg/day
       • Ferritin 2,000-3,000 ng/mL: 35 mg/kg/day
       • Higher ferritin: up to 55 mg/kg/day
     • Monitoring: Monthly ferritin levels, auditory and visual function, renal function

  2. Other chelators (mentioned in guidelines) 4:

     • Deferiprone
     • Deferasirox

• Duration: Continue as long as transfusion therapy is needed or iron overload remains clinically relevant 4

2. Non-Iron Overload Conditions

Treatment should target the underlying cause 6:

• Inflammatory conditions: Treat the primary inflammatory disease
• Metabolic syndrome/obesity: Weight loss, dietary modifications
• Alcoholic liver disease: Alcohol cessation
• Infections: Appropriate antimicrobial therapy

3. Special Populations

Myelodysplastic Syndromes (MDS) 4, 7:

• Chelation therapy should be initiated when:
  • Ferritin >1,000 ng/mL
  • Transfusion requirement ≥2 units/month for >1 year
  • Low-risk MDS (IPSS low or intermediate-1)
  • Life expectancy ≥1 year
  • Allogeneic stem cell transplant candidates

Allogeneic Stem Cell Transplant Candidates 4, 7:

• Iron chelation prior to transplant decreases risk of procedure-related hepatic complications
• Higher mortality seen with ferritin levels >1,000 ng/mL at transplant
• Post-transplant: Phlebotomy preferred when hemoglobin is stable (>1 year after transplant)

Monitoring During Treatment

• Iron studies: Every 3 months during initial treatment, then annually after stabilization 1
• Organ function: Regular assessment of cardiac, hepatic, and endocrine function
• Adverse effects: Monitor for medication-specific side effects:
  • Deferoxamine: Auditory/ocular toxicity, renal toxicity, respiratory distress, infections 5

Important Caveats

1. Phlebotomy vs. Chelation: Phlebotomy is preferred for most iron overload conditions except in anemic or transfusion-dependent patients 1

2. Vitamin C Supplementation: May increase iron availability for chelation but should be used cautiously:

   • Avoid in patients with cardiac failure
   • Delay for one month after starting chelation
   • Limit to 200 mg daily in adults
   • Monitor cardiac function 5

3. Referral Indications:

   • Ferritin >1,000 μg/L without clear cause
   • Evidence of organ damage
   • Suspected hereditary hemochromatosis 1, 6

4. Novel Approaches: Recent research suggests lactoferrin (200-400 mg/day) may help reduce ferritin levels in non-hereditary hemochromatosis hyperferritinemia, though more research is needed 8