What is the appropriate management for elevated ferritin levels?

Management of Elevated Ferritin Levels

The management of elevated ferritin levels should focus on identifying and treating the underlying cause while considering both transferrin saturation and ferritin levels together for proper evaluation of iron status. 1

Initial Diagnostic Approach

• Always measure both serum ferritin and transferrin saturation (TS) together to properly evaluate iron status 1
• If TS ≥ 45% and/or elevated ferritin, proceed to HFE genotype testing to evaluate for hereditary hemochromatosis 1
• If TS < 45% with elevated ferritin, evaluate for non-iron overload causes including:
  • Inflammatory conditions (check CRP, ESR) 1
  • Liver disease (check ALT, AST) 1
  • Malignancy 2
  • Chronic kidney disease 3
  • Rheumatologic diseases 1

Management Based on Underlying Cause

Iron Overload Disorders

• For hereditary hemochromatosis with ferritin < 1000 μg/L, initiate therapeutic phlebotomy to achieve ferritin < 50 μg/L 1
• For hereditary hemochromatosis with ferritin > 1000 μg/L, evaluate for liver disease and consider liver biopsy if liver enzymes are elevated and platelets < 200,000/μL 1
• For transfusional iron overload with serum ferritin consistently > 1000 μg/L, consider iron chelation therapy 4
  • Monitor serum ferritin monthly and adjust chelation dose every 3-6 months 4
  • If ferritin falls below 500 μg/L, interrupt chelation therapy and continue monthly monitoring 4

Inflammatory and Secondary Causes

• For inflammatory conditions, treat the underlying condition rather than focusing solely on the elevated ferritin 1
• For chronic kidney disease patients with elevated ferritin (500-1200 ng/mL) but low transferrin saturation (<25%), intravenous iron may still be beneficial for anemia management 3
• For patients with very high ferritin levels (>10,000 ng/mL), consider adult-onset Still's disease, hemophagocytic lymphohistiocytosis, or macrophage activation syndrome 1, 2

Monitoring and Follow-up

• Monitor serum ferritin monthly in patients receiving treatment for iron overload 4
• For patients with secondary causes, monitor based on the underlying condition 1
• For patients with chronic kidney disease receiving iron therapy:
  • Monitor hemoglobin levels, ESA dose, and patient status 3
  • Consider withholding iron when serum ferritin exceeds 1000 ng/mL or transferrin saturation exceeds 50% 3

Special Considerations

Chronic Kidney Disease

• In CKD patients with elevated ferritin (500-1200 ng/mL) and low transferrin saturation (<25%), intravenous iron can still increase hemoglobin levels 3
• Balance the probability of achieving an increase in hemoglobin against the patient's perceived risk when considering iron administration in patients with ferritin levels above 800 ng/mL 3

Liver Assessment

• Consider liver MRI for non-invasive assessment of hepatic iron overload in patients with persistently elevated ferritin 5
• T2 and T2* relaxometry are considered the standard of care for measuring liver iron content 5
• Consider referral to a specialist if serum ferritin is >1000 μg/L and the cause remains unclear 6

Common Pitfalls to Avoid

• Using ferritin alone without transferrin saturation to diagnose iron overload 1
• Overlooking the need for liver biopsy in patients with ferritin > 1000 μg/L and abnormal liver tests 1
• Failing to recognize that patients with hyperferritinemia frequently have multiple underlying conditions 7
• Administering iron supplementation to patients with elevated ferritin without considering transferrin saturation 1