How to manage elevated ferritin levels?

Management of Elevated Ferritin Levels

The management of elevated ferritin levels requires a systematic diagnostic approach to differentiate between true iron overload and inflammatory hyperferritinemia, with treatment tailored to the underlying cause. 1

Diagnostic Evaluation

Initial Assessment

• Complete iron studies panel including:
  • Serum ferritin
  • Serum iron
  • Total iron binding capacity
  • Transferrin saturation (crucial differentiating test)
• Complete liver biochemistry panel
• Inflammatory markers (C-reactive protein)
• Assessment for other causes of liver disease

Interpretation of Results

• Transferrin saturation is the key differentiating factor:
  • Normal transferrin saturation (<45%): Likely inflammatory hyperferritinemia
  • Elevated transferrin saturation (>45% in females, >50% in males): Possible true iron overload

Additional Testing Based on Initial Results

• If transferrin saturation elevated:
  • HFE gene testing for p.C282Y mutations (especially in European ancestry)
  • Consider liver biopsy or MRI to assess hepatic iron concentration
• If normal transferrin saturation:
  • Focus on identifying inflammatory causes (NAFLD, alcohol excess, infections, malignancy)

Management Algorithm

1. For Normal Transferrin Saturation (<45%)

• Focus on treating the underlying cause:
  • NAFLD management: weight loss, blood pressure control
  • Alcohol cessation if applicable
  • Treatment of underlying inflammatory condition
• Monitor ferritin and liver function tests regularly
• No phlebotomy needed unless specific indications

2. For Elevated Transferrin Saturation (>45-50%)

• Therapeutic phlebotomy is the primary treatment for confirmed iron overload 1

  • Initial frequency: weekly phlebotomy (400-500 mL, containing 200-250 mg iron)
  • Target ferritin level: 50-100 μg/L
  • Monitor ferritin and transferrin saturation every 3 months during initial treatment
  • Once stabilized, monitor at least annually

• Iron chelation therapy (e.g., deferasirox) when phlebotomy is contraindicated 1, 2

  • Starting dose: 14 mg/kg/day for patients with eGFR >60 mL/min/1.73m²
  • Monitor serum ferritin monthly to adjust dose
  • Target ferritin level: 500-1000 μg/L
  • Monitor blood counts, liver function, and renal function monthly
  • Dose adjustments based on serum ferritin trends

3. Lifestyle Modifications for All Patients

• Weight loss if overweight
• Regular physical activity
• Dietary modifications:
  • Reduce red meat consumption
  • Limit alcohol intake
  • Avoid iron supplements and iron-fortified foods
  • Limit vitamin C supplements to 500 mg/day

Common Causes of Elevated Ferritin

1. Inflammatory conditions (most common cause) 3, 4

   • Non-alcoholic fatty liver disease (NAFLD)
   • Infections
   • Malignancy
   • Rheumatic conditions (e.g., adult-onset Still's disease)
   • Kidney failure

2. Iron overload disorders 4

   • Hereditary hemochromatosis (HFE gene mutations)
   • Secondary iron overload (thalassemia, myelodysplastic syndrome, multiple transfusions)
   • Dysmetabolic iron overload syndrome

Important Considerations and Pitfalls

• Don't assume all elevated ferritin represents iron overload - ferritin is an acute phase reactant and often reflects inflammation rather than iron excess 5, 6

• Don't initiate phlebotomy without confirming true iron overload - unnecessary phlebotomy in patients with inflammatory hyperferritinemia can lead to anemia

• Watch for signs of organ damage - elevated liver enzymes and metacarpophalangeal joint arthropathy are important predictors of significant iron overload 7

• Monitor for overchelation in patients receiving treatment - if serum ferritin falls below 1000 μg/L at 2 consecutive visits, consider dose reduction; if below 500 μg/L, interrupt therapy 1, 2

• Early identification and treatment before development of cirrhosis and/or diabetes significantly reduces morbidity and mortality 1