Management of Elevated Ferritin Levels
The management of elevated ferritin requires a systematic diagnostic approach to differentiate between true iron overload and inflammatory hyperferritinemia, with treatment directed at the underlying cause. 1
Diagnostic Evaluation
Initial Assessment
- Complete iron studies panel including:
- Serum ferritin
- Serum iron
- Total iron binding capacity
- Transferrin saturation (crucial for differentiating true iron overload from inflammatory hyperferritinemia)
- Complete liver biochemistry panel
- Assessment for other causes of liver disease
- Inflammatory markers (C-reactive protein)
Interpretation of Ferritin Levels
| Ferritin Level | Interpretation |
|---|---|
| <30 μg/L | Iron deficiency in the absence of inflammation |
| 30-100 μg/L | Possible iron deficiency or anemia of chronic disease with inflammation |
| >100 μg/L | Anemia of chronic disease or iron overload |
Management Algorithm
1. If Transferrin Saturation is Normal (<45%)
- Focus on managing underlying inflammatory condition
- Most common cause: Non-alcoholic fatty liver disease (NAFLD)
- Management includes:
- Weight loss
- Blood pressure control
- Regular monitoring of liver function tests
- Addressing metabolic risk factors
2. If Transferrin Saturation is Elevated (>45% in females, >50% in males)
- Perform HFE gene testing for p.C282Y mutations (especially in patients with European ancestry)
- Consider liver biopsy to assess:
- Hepatic iron concentration
- Pattern of iron deposition
- Degree of fibrosis and inflammation
- MRI can be used to detect and quantify hepatic iron excess
3. Treatment of Confirmed Iron Overload
Therapeutic phlebotomy is the primary treatment:
- 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
- Annual monitoring once stabilized 1
Iron chelation therapy (e.g., deferasirox) when phlebotomy is contraindicated:
Special Considerations
Dosage Adjustments for Deferasirox
- For patients with hepatic impairment:
- Mild (Child-Pugh A): No dose adjustment necessary
- Moderate (Child-Pugh B): Reduce starting dose by 50%
- Severe (Child-Pugh C): Avoid deferasirox 2
Risk of Overchelation
- If serum ferritin falls below 1000 μg/L at 2 consecutive visits, consider dose reduction
- If serum ferritin falls below 500 μg/L, interrupt therapy and monitor monthly
- Use minimum effective dose to maintain iron burden in target range 2
Lifestyle Modifications
- Weight loss for overweight patients
- 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 1
Common Causes of Hyperferritinemia
Inflammatory conditions (most common):
Iron overload disorders:
- Hereditary hemochromatosis (HFE gene mutations)
- Secondary iron overload (thalassemia, myelodysplastic syndrome, multiple transfusions) 4
Other causes:
Clinical Pearls and Pitfalls
- Elevated ALT levels and metacarpophalangeal joint arthropathy are independently associated with elevated ferritin levels in patients with hemochromatosis 6
- Serum ferritin can be a marker of cellular damage, not just iron overload, as it is often a leakage product from damaged cells 7
- Early identification and treatment before development of cirrhosis and/or diabetes significantly reduces morbidity and mortality 1
- Dysmetabolic iron overload syndrome is common in alcohol excess, NAFLD, and other chronic liver diseases, and does not reflect hereditary hemochromatosis 1, 5
- Avoid simply rechecking ferritin in three weeks without further evaluation, as elevated ferritin warrants immediate assessment 1