What is the treatment for hyperferritinemia (elevated iron levels)?

Treatment of Hyperferritinemia (Elevated Iron Levels)

Therapeutic phlebotomy is the cornerstone of treatment for confirmed hemochromatosis with elevated iron levels, with a target ferritin level below 500 μg/L to prevent organ damage. 1

Diagnostic Approach Before Treatment

• Initial assessment must include both transferrin saturation and serum ferritin measurements to distinguish true iron overload from other causes of isolated hyperferritinemia 2
• Genetic testing for HFE mutations (particularly C282Y and H63D) should be performed in individuals with biochemical evidence of iron overload (transferrin saturation >45% in females or >50% in males with elevated ferritin) 2, 1
• MRI should be used to quantify hepatic iron concentrations in patients with unclear cause of hyperferritinemia or biochemical iron overload 2, 3
• Liver biopsy should be considered if serum ferritin exceeds 1,000 μg/L or if liver enzymes are elevated to assess for fibrosis/cirrhosis 2, 1

Treatment Algorithm

For Confirmed Hemochromatosis:

1. First-line treatment: Therapeutic phlebotomy 2, 1

   • Initial phase: Remove 400-500 mL of blood (containing approximately 200-250 mg iron) weekly until ferritin <500 μg/L 1
   • Monitor hemoglobin before each phlebotomy; if anemia develops despite elevated ferritin, extend the phlebotomy interval 1
   • Once target ferritin is reached, maintenance phlebotomies typically needed 3-4 times per year 1

2. For patients unable to tolerate phlebotomy:

   • Consider iron chelation therapy with deferasirox 4
   • Starting dose based on transfusion history and current iron burden 4
   • Monitor for potential adverse effects including renal dysfunction, hepatotoxicity, and gastrointestinal disturbances 4
   • Discontinue if severe skin reactions or hypersensitivity occurs 4

For Secondary Iron Overload (e.g., transfusion-dependent disorders):

1. Iron chelation therapy 2, 4
   • Deferasirox is FDA-approved for transfusional iron overload 4
   • Monitor serum ferritin monthly to assess for possible overchelation 4
   • If ferritin falls below 1,000 μg/L, consider dose reduction 4
   • If ferritin falls below 500 μg/L, interrupt therapy 4

Monitoring During Treatment

• Regular monitoring of ferritin levels and transferrin saturation every 3 months during treatment 2, 1
• Monitor liver and renal function more frequently during volume depletion and in patients receiving higher doses of chelation therapy 4
• Perform auditory and ophthalmic testing before starting deferasirox treatment and thereafter at regular intervals (every 12 months) 4
• Monitor blood counts in all patients receiving chelation therapy due to risk of bone marrow suppression 4

Special Considerations

• For patients with ferritin >1,000 μg/L, there is increased risk of hepatic fibrosis/cirrhosis requiring more aggressive treatment 2, 1
• First-degree relatives of patients with confirmed hemochromatosis should be screened with serum ferritin, transferrin saturation, and HFE genetic testing 2, 1
• Distinguish between true iron overload and conditions causing isolated hyperferritinemia without iron overload (inflammation, malignancy, liver disease) 5, 6
• In patients with dysmetabolic hyperferritinemia (normal transferrin saturation with high ferritin), focus on treating underlying metabolic disorders rather than iron removal 5, 7

Potential Complications to Monitor

• Liver fibrosis/cirrhosis in patients with ferritin >1,000 μg/L 2
• Cardiac complications requiring cardiac MRI assessment in advanced cases 2, 3
• Endocrine abnormalities including diabetes mellitus 1, 6
• Arthropathy and joint pain 1
• Potential adverse effects from chelation therapy including renal dysfunction, hepatotoxicity, and auditory/ocular abnormalities 4