How to treat elevated ferritin levels?

Management of Elevated Ferritin Levels

The first step in treating elevated ferritin levels is to determine the underlying cause through evaluation of both ferritin and transferrin saturation, with values >1000 ng/mL and >45% respectively suggesting true iron overload requiring therapeutic intervention. 1

Diagnostic Approach

• Evaluate both ferritin and transferrin saturation together to identify the underlying cause, as elevated ferritin can occur in various conditions including iron overload, inflammation, malignancy, and liver disease 1, 2
• Consider HFE gene testing for C282Y and H63D mutations in patients with elevated ferritin and transferrin saturation to diagnose hereditary hemochromatosis 1
• Investigate common non-iron overload causes (90% of cases) including:
  • Alcohol consumption
  • Metabolic syndrome and obesity
  • Diabetes
  • Liver disease
  • Malignancy (most common cause of markedly elevated ferritin)
  • Infection or inflammation 2, 3
• Referral to a specialist (gastroenterologist, hematologist) is appropriate if serum ferritin is >1000 μg/L or if the cause remains unclear 3

Treatment Algorithm Based on Cause

For Primary Iron Overload (Hemochromatosis)

• Therapeutic phlebotomy is the cornerstone of treatment for confirmed hemochromatosis 1
  • Initial schedule: weekly removal of one unit of blood (450-500 mL, containing 200-250 mg iron)
  • Target ferritin level: 50-100 μg/L
  • Maintenance phlebotomy (3-4 times per year) once target is reached 1

For Secondary Iron Overload

• Consider iron chelation therapy when serum ferritin levels reach 1,000 ng/mL or with high transfusion requirements 1
• Options include:
  • Deferasirox (oral): Monitor for potential adverse effects including renal dysfunction, hepatic impairment, and gastrointestinal symptoms 4
  • Deferoxamine (subcutaneous/intravenous): Watch for auditory and ocular toxicity, especially with prolonged use 5
• Interrupt chelation therapy if serum ferritin falls below 500 mcg/L to avoid overchelation 4

For Elevated Ferritin in Chronic Kidney Disease

• For patients with elevated ferritin but low transferrin saturation (<25%), intravenous iron may still be beneficial, especially if they are on erythropoietin therapy 6
• In dialysis patients with ferritin 500-1200 ng/mL and transferrin saturation <25%, intravenous iron can improve hemoglobin levels 6
• Consider withholding iron therapy when ferritin exceeds 1000 ng/mL or transferrin saturation exceeds 50% 6

For Inflammatory Conditions

• Treat the underlying inflammatory condition rather than the elevated ferritin directly 2, 7
• Recognize that extremely high ferritin levels (>10,000 μg/L) may be associated with conditions like adult-onset Still's disease, systemic juvenile idiopathic arthritis, or hemophagocytic lymphohistiocytosis 2

Monitoring Recommendations

• Regular monitoring of ferritin levels during treatment is essential 1
• For patients on iron chelation therapy, monitor:
  • Renal function and hepatic function
  • Auditory and ophthalmic testing (including slit lamp examinations and dilated fundoscopy) before starting treatment and at regular intervals (every 12 months) 4
• For patients with chronic kidney disease receiving iron therapy, monitor hemoglobin levels, ESA dose, and iron parameters 6

Important Caveats

• Multiple conditions often contribute to hyperferritinemia in the same patient, with higher levels typically seen in those with multiple underlying causes 7
• Extremely elevated ferritin levels can occur in seemingly indolent disease or with chronic inflammation 2
• Some research suggests that optimal ferritin levels for cardiovascular mortality reduction may range from 20 to 100 ng/mL with transferrin saturation from 20 to 50% 8
• Non-invasive MRI is now considered the standard method to diagnose and monitor hepatic iron overload, avoiding the need for liver biopsy in most cases 9