How is elevated ferritin treated?

Treatment of Elevated Ferritin

Therapeutic phlebotomy is the first-line treatment for elevated ferritin associated with iron overload conditions such as hereditary hemochromatosis, while underlying causes should be addressed for secondary hyperferritinemia. 1

Diagnostic Approach to Elevated Ferritin

Before initiating treatment, it's crucial to determine whether hyperferritinemia represents true iron overload or is secondary to other conditions:

1. Initial Assessment:

   • Measure transferrin saturation (TS) alongside ferritin
   • If TS ≥45% and elevated ferritin: suggests iron overload
   • If TS <45% with elevated ferritin: likely secondary cause 1

2. Common Causes of Elevated Ferritin:

   • Iron overload disorders: Hereditary hemochromatosis (HH), transfusion-dependent anemias
   • Inflammatory conditions: Infections, autoimmune diseases, malignancies
   • Liver disease: Alcoholic liver disease, viral hepatitis, NAFLD
   • Other causes: Metabolic syndrome, renal failure, malignancy 2, 3

3. Important note: In the general population, iron overload is NOT the most common cause of elevated ferritin 1

Treatment Algorithm Based on Cause

1. Iron Overload Conditions (TS ≥45%, elevated ferritin)

• Primary treatment: Therapeutic phlebotomy

  • Remove 400-500 mL of blood (200-250 mg iron) weekly until target ferritin achieved
  • Target ferritin: <500 μg/L (to avoid toxicity, especially in children/adolescents) 1
  • Monitor ferritin and hemoglobin levels regularly
  • Adjust frequency based on patient tolerance and ferritin response 1

• For patients who cannot tolerate phlebotomy:

  • Iron chelation therapy with:
    • Deferasirox (oral) - monitor for renal function, auditory/ocular abnormalities 4
    • Deferoxamine (parenteral) - monitor for hypersensitivity, renal toxicity 5

• Special considerations:

  • If anemia develops during phlebotomy despite elevated ferritin (as in ferroportin disease):
    • Extend phlebotomy interval
    • Consider erythropoietin supplementation 1

2. Secondary Hyperferritinemia (TS <45%, elevated ferritin)

• Primary approach: Treat underlying condition 1, 6

  • Inflammatory conditions: Treat infection, autoimmune disease
  • Liver disease: Manage hepatitis, alcohol cessation, weight loss for NAFLD
  • Metabolic syndrome: Weight loss, glycemic control, lipid management
  • Malignancy: Appropriate cancer therapy

• Monitoring:

  • Repeat ferritin and TS 4-8 weeks after treating underlying condition
  • If ferritin remains elevated, consider additional evaluation 1

3. Chronic Kidney Disease with Elevated Ferritin

• For CKD patients:
  • Continue iron therapy if ferritin 100-800 ng/mL with low TSAT (<20%)
  • Consider temporary discontinuation if ferritin >800 ng/mL AND TSAT >50%
  • IV iron may be preferred over oral iron for functional iron deficiency 7

Monitoring Treatment Response

• For iron overload conditions:

  • Monitor ferritin every 2-3 months during intensive phlebotomy
  • Once target achieved, monitor every 6-12 months
  • Consider liver MRI for accurate assessment of iron stores in unclear cases 2

• For secondary causes:

  • Monitor ferritin 4-8 weeks after treating underlying condition
  • Do not check iron parameters within 4 weeks of IV iron administration (may give false results) 1

Common Pitfalls to Avoid

1. Assuming all elevated ferritin represents iron overload - most cases in general practice are due to inflammation, infection, or liver disease 3, 8

2. Initiating phlebotomy without confirming iron overload - can worsen anemia in patients with inflammatory conditions

3. Overlooking multiple causes - 41% of patients with hyperferritinemia have multiple contributing factors 8

4. Failing to recognize hereditary causes - conditions like hereditary hyperferritinemia-cataract syndrome can present with very high ferritin but normal iron stores 9

5. Overtreating with phlebotomy - excessive phlebotomy can lead to anemia; monitor hemoglobin closely

By following this algorithmic approach and addressing the underlying cause of elevated ferritin, clinicians can effectively manage this common laboratory finding while minimizing complications from inappropriate treatment.