What is the management approach for a patient with hyperferritinemia and a normal complete blood count (CBC)?

Management of Hyperferritinemia with Normal CBC

Patients with elevated ferritin and normal CBC require a systematic diagnostic approach to identify the underlying cause, as hyperferritinemia can indicate iron overload conditions requiring specific treatment or reflect inflammatory states not requiring iron removal.

Diagnostic Approach

Initial Evaluation

• Complete iron studies are essential, including:
  • Serum iron
  • Total iron binding capacity (TIBC)
  • Transferrin saturation (TSAT)
  • Ferritin 1

Interpretation of Results

1. If TSAT is elevated (>45%):

   • Consider hereditary hemochromatosis
   • Genetic testing for HFE gene mutations is indicated 2
   • Evaluate for organ damage (liver function tests, glucose)

2. If TSAT is normal or low (<20%) with elevated ferritin:

   • Consider non-iron overload causes:
     • Inflammatory conditions
     • Liver disease (hepatitis, alcoholic liver disease, NAFLD)
     • Malignancy
     • Infection
     • Metabolic syndrome/obesity 3

Additional Testing Based on Clinical Suspicion

• Liver function tests
• Inflammatory markers (CRP, ESR)
• Glucose, lipid profile (for metabolic syndrome)
• Hepatitis serology
• Alcohol use assessment

Management Strategy

For Iron Overload Conditions (elevated TSAT and ferritin)

1. Therapeutic phlebotomy:

   • Initial frequency: weekly phlebotomy (400-500 mL)
   • Target ferritin level: 50-100 μg/L 1
   • Monitor ferritin and TSAT every 3 months during initial treatment

2. When phlebotomy is contraindicated:

   • Consider iron chelation therapy (e.g., deferasirox)
   • Starting dose: 14 mg/kg/day for patients with eGFR >60 mL/min/1.73m²
   • Monitor ferritin monthly to adjust dose 1, 4

For Non-Iron Overload Conditions (normal TSAT with elevated ferritin)

• Address underlying cause:

  • Treat inflammatory conditions
  • Manage metabolic syndrome with lifestyle modifications
  • Treat liver disease
  • Address infections

• Lifestyle modifications:

  • Weight loss if overweight/obese
  • Regular physical activity
  • Dietary modifications (reduce red meat consumption)
  • Limit alcohol intake
  • Avoid iron supplements 1

When to Refer

• Ferritin >1000 μg/L
• Unclear etiology after initial workup
• Evidence of organ damage
• Suspected hemochromatosis requiring specialized management 3

Important Considerations

• 90% of elevated ferritin cases are due to non-iron overload conditions where phlebotomy is not appropriate 3
• Extremely high ferritin levels (>10,000 μg/L) may suggest rare conditions like hemophagocytic lymphohistiocytosis or adult-onset Still's disease 5, 6
• Avoid iron supplementation without confirmed iron deficiency, as it may be harmful 1
• Regular monitoring is essential for patients with persistent hyperferritinemia

Common Pitfalls to Avoid

1. Initiating phlebotomy without confirming iron overload
2. Failing to investigate non-iron overload causes of hyperferritinemia
3. Missing hereditary causes of hyperferritinemia with normal transferrin saturation 7
4. Overlooking metabolic syndrome as a common cause of elevated ferritin
5. Not recognizing that ferritin is an acute-phase reactant that increases with inflammation

Regular monitoring of iron studies is recommended for all patients with hyperferritinemia, with frequency determined by the underlying cause and treatment approach.