How to manage hyperferritinemia?

Management of High Ferritin Levels (Hyperferritinemia)

Therapeutic phlebotomy is the mainstay of treatment for hyperferritinemia, with a target ferritin level of 50-100 μg/L to prevent complications related to iron overload. 1

Diagnostic Approach to Hyperferritinemia

• Evaluate for underlying causes of hyperferritinemia, as only about 10% of cases are related to true iron overload disorders like hemochromatosis 2
• Key diagnostic tests include:
  • Serum ferritin and transferrin saturation (initial screening) 1
  • Consider genetic testing for HFE mutations in suspected hereditary hemochromatosis 1
  • Liver function tests to assess for liver damage 1
  • Consider cardiac evaluation in cases of suspected cardiac involvement 3

Treatment Algorithm Based on Etiology

For Hereditary Hemochromatosis and Primary Iron Overload:

• Initial Treatment (Induction Phase):

  • Weekly therapeutic phlebotomy (removal of 450-500 mL of blood) as tolerated 1, 3
  • Monitor hemoglobin at each phlebotomy session 1
  • Reduce frequency if hemoglobin <12 g/dL; discontinue if <11 g/dL 1
  • Monitor serum ferritin monthly or after every 4th phlebotomy 1
  • When ferritin decreases below 200 μg/L, check levels every 1-2 sessions 1

• Target for Induction Phase:

  • Reduce serum ferritin to <50 μg/L 1

• Maintenance Phase:

  • Continue phlebotomy every 3-6 months to maintain ferritin between 50-100 μg/L 1
  • Monitor ferritin every 6 months 1
  • Investigate unexpected fluctuations in ferritin or transferrin saturation 1

For Secondary Iron Overload:

• In Anemic Patients (e.g., thalassemia, myelodysplastic syndromes):

  • Iron chelation therapy with deferasirox or deferoxamine when phlebotomy is not feasible 1, 4
  • Caution: Deferasirox is contraindicated in patients with poor renal function (eGFR <40 mL/min/1.73m²) 4
  • Monitor for renal and hepatic toxicity with chelation therapy 4

• In Non-Anemic Secondary Iron Overload:

  • Consider phlebotomy for conditions like NAFLD with hyperferritinemia 1, 5
  • Phlebotomy has shown benefit in improving insulin resistance in NAFLD patients 5
  • Phlebotomy is effective in reducing iron overload in long-term survivors of acute leukemia 6

Special Considerations for NAFLD/NASH

• Consider therapeutic phlebotomy when ferritin exceeds 1000 μg/L, especially with elevated liver enzymes 7
• A ferritin level >1000 μg/L with elevated liver enzymes and platelet count <200 predicts cirrhosis in 80% of C282Y homozygous patients 7

Dietary and Lifestyle Modifications

• Important dietary considerations:

  • Dietary modifications should not substitute for iron removal therapy 1
  • Avoid iron supplements and iron-fortified foods 1
  • Avoid supplemental vitamin C, especially before iron depletion 1
  • Limit red meat consumption 1
  • Consume fruit juices and citrus fruits in moderation, not with other foods 1

• Alcohol consumption:

  • Restrict alcohol intake during iron depletion phase 1
  • Patients with iron overload and liver abnormalities should avoid or minimize alcohol 1
  • Complete abstinence from alcohol is recommended for patients with cirrhosis 1

• Other precautions:

  • Avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection in iron overload states 1
  • Monitor folate and vitamin B12 levels in patients requiring numerous phlebotomies 1

Monitoring and Follow-up

• Monitor hemoglobin and hematocrit at each phlebotomy session 1
• Periodically check plasma folate and cobalamin levels, especially in patients requiring numerous venesections 1
• For patients on iron chelation therapy, regular monitoring of renal function, liver function, and auditory and visual function is essential 4

Pitfalls and Caveats

• Extremely high ferritin levels (>10,000 μg/L) are rarely due to isolated iron overload syndromes and more commonly associated with conditions like infections, hemophagocytic lymphohistiocytosis, or acute hepatitis 8
• Avoid overtreatment with phlebotomy, which can lead to iron deficiency anemia 1
• Recognize that arthralgia may not improve with iron depletion in hemochromatosis 1
• In elderly patients, investigate for conditions that may lead to iron loss (peptic ulcers, colonic disease, hematuria) if iron reaccumulation is slower than expected 1