What is the treatment for elevated ferritin levels?

Treatment of Elevated Ferritin Levels

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

Diagnostic Approach Before Treatment

Before initiating treatment for elevated ferritin, it's crucial to determine whether the elevation represents true iron overload or is secondary to other causes:

1. Initial evaluation:

   • Measure transferrin saturation (TS) alongside ferritin
   • If TS ≥ 45% and/or ferritin is elevated, proceed with HFE gene testing 1
   • Check inflammatory markers (CRP, ESR) to identify inflammatory causes 2

2. Interpretation of results:

   • TS < 20% with elevated ferritin: Suggests functional iron deficiency or anemia of inflammation
   • TS ≥ 20% and < 50% with elevated ferritin: Likely non-iron overload causes
   • TS > 50% with elevated ferritin: Suggests iron overload 2

Treatment Algorithm Based on Cause

1. Iron Overload (Hemochromatosis)

• Primary treatment: Weekly therapeutic phlebotomy (removal of 500 mL blood) 1
• Monitoring during treatment:
  • Check hemoglobin/hematocrit before each phlebotomy
  • Allow hematocrit to fall by no more than 20% of prior level
  • Check serum ferritin every 10-12 phlebotomies
  • Stop frequent phlebotomy when ferritin reaches 50-100 μg/L 1
• Maintenance phase:
  • Continue phlebotomy at intervals to keep ferritin between 50-100 μg/L
  • Monitor serum ferritin every 6 months to adjust treatment schedule 1

2. Secondary Iron Overload

• For transfusional iron overload:
  • Consider iron chelation therapy with deferasirox if:
    • Patient has received at least 100 mL/kg of packed RBCs
    • Serum ferritin consistently >1000 μg/L 3
  • Dosing: 14 mg/kg/day orally (adjust based on response) 3
  • Interrupt therapy if ferritin falls below 500 μg/L 3

3. Inflammatory or Non-Iron Overload Causes

• Primary approach: Treat the underlying condition
• Common causes to investigate:
  • Infections
  • Malignancies
  • Liver dysfunction
  • Renal failure
  • Inflammatory conditions 4, 5

Dietary and Lifestyle Modifications

For patients with confirmed iron overload:

• Avoid iron supplementation and iron-fortified foods 1
• Limit red meat consumption 1
• Avoid vitamin C supplements, especially before iron depletion 1
• Restrict alcohol intake during iron depletion phase 1
• Patients with cirrhosis should abstain from alcohol completely 1
• Avoid raw shellfish due to risk of Vibrio vulnificus infection 1

Monitoring Response to Treatment

• During induction phase:

  • Monitor hemoglobin at each phlebotomy session
  • Measure ferritin monthly or after every 4th phlebotomy
  • When ferritin decreases below 200 μg/L, check after every 1-2 sessions 1

• During maintenance phase:

  • Monitor ferritin every 6 months
  • Adjust phlebotomy frequency to maintain target ferritin (50-100 μg/L) 1
  • Monitor folate and cobalamin levels periodically 1

Special Considerations

• Avoid phlebotomy if:

  • Hemoglobin <11 g/dL (discontinue and reassess) 1
  • Patient has anemia from other causes
  • Elevated ferritin is due to inflammation without iron overload 2

• Risk of overtreatment:

  • Depletion of iron stores (ferritin <50 μg/L) can increase dietary iron absorption 1
  • Symptomatic iron deficiency can develop in patients with hemochromatosis 1

Common Pitfalls

• Initiating phlebotomy based solely on ferritin without checking transferrin saturation 2
• Starting phlebotomy for mildly elevated ferritin without evidence of iron overload 2
• Ignoring underlying causes of hyperferritinemia (only 10% of cases relate to iron overload) 6
• Failing to recognize that patients with hyperferritinemia frequently have multiple underlying conditions 5

By following this structured approach, the appropriate treatment for elevated ferritin can be determined based on the underlying cause, with therapeutic phlebotomy being the mainstay for confirmed iron overload conditions.