What is the treatment for hyperferritinemia?

Treatment of Hyperferritinemia

The treatment of hyperferritinemia must be directed at the underlying cause, with therapeutic phlebotomy being the primary treatment for iron overload conditions targeting a ferritin level of 50-100 μg/L. 1

Diagnostic Approach to Hyperferritinemia

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

1. Common causes of hyperferritinemia 2, 3:

   • Iron overload disorders (hemochromatosis)
   • Inflammation/infection
   • Chronic alcohol consumption
   • Cell necrosis (check AST, ALT, CK)
   • Malignancies (particularly lymphomas)
   • Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome
   • Adult-onset Still's disease (AOSD)
   • Hemophagocytic lymphohistiocytosis (HLH)

2. Initial evaluation:

   • Complete iron studies (ferritin, transferrin saturation)
   • Inflammatory markers (CRP, ESR)
   • Liver function tests
   • Blood count and differential
   • Metabolic panel (glucose, lipids, blood pressure)
   • Consider glycosylated ferritin fraction if available 2

Treatment Algorithm Based on Etiology

1. Iron Overload Conditions (e.g., Hemochromatosis)

Primary treatment: Therapeutic phlebotomy 1

• Initial phase: Remove one unit of blood (450-500 mL) weekly as tolerated
• Target: Ferritin level of 50-100 μg/L
• Maintenance phase: Phlebotomy every 1-4 months to maintain target ferritin
• Monitoring: Check hemoglobin before each phlebotomy; ferritin after every 10-12 phlebotomies initially, then more frequently as target approaches

Alternative: Erythrocytapheresis 1

• More efficient removal of red blood cells (up to 1000 mL vs. 250 mL per session)
• Cost-effective in induction phase due to fewer required interventions

2. Iron Chelation Therapy

Indications 1:

• Serum ferritin levels >1,000 ng/mL
• Transfusion dependency (≥2 units/month for >1 year)
• Low-risk myelodysplastic syndromes
• Life expectancy of at least one year

Options:

• Deferasirox (oral) 4

  • Contraindicated in patients with eGFR <40 mL/min/1.73m²
  • Monitor for renal toxicity, hepatic injury, and GI ulceration
  • Dose reduction needed for moderate hepatic impairment

• Deferoxamine (subcutaneous/intravenous) 1

  • Consider for patients who cannot tolerate oral therapy

Monitoring during chelation therapy 1:

• Serum ferritin every 3 months (monthly if possible)
• Liver function tests regularly
• Renal function (especially with deferasirox)
• Consider auditory and visual testing for patients on deferoxamine

3. Inflammatory/Reactive Hyperferritinemia

Treatment focuses on underlying condition 3, 5:

• NAFLD/Metabolic syndrome: Lifestyle modifications (weight loss, exercise)
• Adult-onset Still's disease: Anti-inflammatory agents, corticosteroids 2
• Hemophagocytic lymphohistiocytosis: HLH-directed therapy based on trigger 2
• Infection/inflammation: Treat underlying infection or inflammatory condition

Important: Phlebotomy is not effective and should not be used when hyperferritinemia is related to inflammation without iron overload 5

4. Malignancy-Associated Hyperferritinemia

• Treatment of the underlying malignancy is the priority 2
• Consider iron chelation therapy for patients with transfusion-dependent malignancies 1

Dietary and Lifestyle Recommendations

For patients with confirmed iron overload 1:

• Avoid iron-fortified foods
• Limit consumption of red meat
• Avoid raw shellfish (increased risk of Vibrio vulnificus infection)
• Moderate consumption of fruit juices and citrus fruits (enhance iron absorption)
• Limit vitamin C supplementation to <500 mg/day during treatment

Common Pitfalls to Avoid

1. Misinterpreting elevated ferritin as iron overload when it could be due to inflammation 1
2. Initiating phlebotomy for all cases of hyperferritinemia without determining if true iron overload exists 5
3. Overlooking occult malignancies, particularly lymphomas, as a cause of hyperferritinemia 2
4. Overtreatment leading to iron deficiency (ferritin <50 μg/L) 1
5. Neglecting to evaluate for other causes of elevated ferritin (inflammation, NAFLD, alcohol) 2

Long-term Follow-up

• Regular monitoring of serum ferritin levels
• Screening for hepatocellular carcinoma in patients with cirrhosis
• Monitoring for complications of iron overload
• Life-long follow-up for patients with genetic hemochromatosis 1

Remember that hyperferritinemia is a common finding in clinical practice, and in only about 10% of cases is it related to true iron overload 6. Determining the underlying cause is essential for appropriate management and avoiding unnecessary treatments.