What is the treatment for elevated ferritin levels?

Treatment for Elevated Ferritin Levels

The treatment for elevated ferritin levels should be based on determining the underlying cause, with therapeutic phlebotomy (removal of 500 mL blood weekly) being the primary treatment for confirmed iron overload, while avoiding intervention for inflammatory-mediated hyperferritinemia without true iron overload. 1

Diagnostic Approach Before Treatment

Before initiating any treatment, proper diagnosis is essential:

1. Initial evaluation:

   • Measure transferrin saturation (TSAT) alongside ferritin
   • Check inflammatory markers (CRP, ESR)
   • Complete blood count to assess for anemia
   • Liver function tests and renal function tests

2. Interpretation of results:

   • TSAT > 50% suggests iron overload → Consider genetic testing for hereditary hemochromatosis
   • Normal TSAT with elevated ferritin → Likely inflammatory-mediated hyperferritinemia
   • Evaluate for secondary causes of iron overload

Treatment Algorithm Based on Diagnosis

For Confirmed Iron Overload (TSAT > 50%)

1. First-line treatment: Weekly therapeutic phlebotomy (removal of 500 mL blood) 1

   • Monitor hemoglobin/hematocrit before each phlebotomy
   • Allow hematocrit to fall by no more than 20% of prior level
   • Check serum ferritin every 10-12 phlebotomies

2. Contraindications to phlebotomy: 1

   • Hemoglobin <11 g/dL
   • Patient has anemia from other causes

3. Iron chelation therapy (for patients who cannot undergo phlebotomy):

   • Deferasirox: Monitor for:

     • Bone marrow suppression (neutropenia, agranulocytosis, worsening anemia) 2
     • Renal toxicity and hepatic dysfunction
     • Risk of overchelation if serum ferritin falls below 1000 mcg/L

   • Deferoxamine: Monitor for:

     • Auditory and ocular toxicity, especially with prolonged use 3
     • Renal toxicity and respiratory distress
     • Growth suppression in pediatric patients

For Inflammatory-Mediated Hyperferritinemia (Normal TSAT)

1. Treat the underlying condition:

   • Infections
   • Malignancies
   • Chronic inflammatory diseases
   • Liver disease

2. Avoid unnecessary phlebotomy or chelation 1

Monitoring and Maintenance

1. During iron depletion phase:

   • Monitor hemoglobin at each phlebotomy session
   • Measure ferritin monthly or after every 4th phlebotomy
   • When ferritin decreases below 200 μg/L, check after every 1-2 sessions 1

2. Maintenance phase:

   • Monitor ferritin every 6 months
   • Adjust phlebotomy frequency to maintain target ferritin (50-100 μg/L)
   • Monitor folate and cobalamin levels periodically 1

Lifestyle Modifications for Iron Overload

For patients with confirmed iron overload: 1

• Avoid iron supplementation and iron-fortified foods
• Limit red meat consumption
• Avoid vitamin C supplements
• Restrict alcohol intake during iron depletion phase
• Patients with cirrhosis should abstain from alcohol completely

Important Considerations and Pitfalls

1. Avoid treating based on ferritin alone:

   • Ferritin is an acute phase reactant and can be elevated in many conditions without iron overload 4, 5
   • Common causes of elevated ferritin include infections, malignancies, liver disease, and renal failure 5, 6

2. Risk of overchelation:

   • Monitor serum ferritin monthly to assess for possible overchelation 2
   • Consider dose reduction if ferritin falls below 1000 mcg/L
   • Interrupt therapy if ferritin falls below 500 mcg/L 2

3. Recognize non-iron overload causes of markedly elevated ferritin:

   • Malignancy is the most common cause of markedly elevated ferritin (>1000 μg/L) 4
   • Patients with hyperferritinemia frequently have multiple underlying conditions 5

4. Target parameters: 1

   • TSAT: ≥ 20%
   • Ferritin: ≥ 100 ng/mL
   • Hemoglobin: 11.0-12.0 g/dL

By following this approach, clinicians can appropriately manage elevated ferritin levels while avoiding unnecessary interventions for patients without true iron overload.