Treatment of Elevated Ferritin Levels
The treatment of elevated ferritin depends entirely on whether true iron overload exists (confirmed by transferrin saturation >45-50%), with phlebotomy for hereditary hemochromatosis, chelation for transfusional overload, and no iron-directed therapy for inflammatory/reactive hyperferritinemia. 1
Initial Diagnostic Workup
The critical first step is measuring transferrin saturation (TSAT) alongside ferritin to distinguish true iron overload from inflammatory states 1:
- TSAT >45-50% with elevated ferritin = true iron overload requiring treatment 1
- TSAT <20% with elevated ferritin = functional iron deficiency or inflammation (no iron removal needed) 1
- Genetic testing for HFE mutations should be performed when TSAT is elevated and clinical suspicion for hereditary hemochromatosis exists 1
Common pitfall: 90% of elevated ferritin cases are NOT due to iron overload 2, 3. The most frequent causes are infection, malignancy, liver dysfunction, renal failure, and metabolic syndrome 4, 5. Inappropriately treating these patients with phlebotomy or chelation causes harm.
Treatment Algorithms by Etiology
For Hereditary Hemochromatosis (HFE-Related)
Phlebotomy is the primary treatment 1:
- Depletion phase: Remove blood regularly until ferritin drops to <50 μg/L to achieve iron deficiency and normalize tissue iron 1
- Maintenance phase: Phlebotomy every 3-6 months to maintain ferritin at 50-100 μg/L 1
For Transfusional Iron Overload
Initiate iron chelation therapy with deferasirox when 1, 6:
- Serum ferritin reaches ≥1000 μg/L in patients requiring ≥2 units/month for >1 year 1
- Starting dose: 14 mg/kg/day orally once daily for patients with eGFR >60 mL/min/1.73 m² 6
- Dose adjustments: Increase in steps of 3.5-7 mg/kg every 3-6 months based on ferritin trends 6
- Maximum dose: 28 mg/kg/day (doses above this are not recommended) 6
- Target: Use minimum effective dose to achieve decreasing ferritin trends 1, 6
Monitoring requirements during chelation 6:
- Monthly ferritin levels 6
- Monthly blood counts, liver function, and renal function 6
- Baseline and annual auditory/ophthalmic examinations 6
For Chronic Kidney Disease with Elevated Ferritin
Do NOT withhold IV iron based solely on elevated ferritin if 1:
- TSAT is low (<25%) AND
- Patient is on erythropoiesis-stimulating agents (ESAs) with inadequate hemoglobin response 1
Target parameters for hemodialysis patients on ESAs 1:
Temporarily withhold IV iron if 1:
- TSAT chronically >50%, OR
- Ferritin >800-1000 ng/mL 1
For Ferroportin Disease
Repeated phlebotomies with extended intervals if anemia develops despite elevated ferritin 1
Critical Safety Considerations
Overchelation Risks (Life-Threatening)
Interrupt chelation therapy when 1, 6:
- Ferritin falls below 500 μg/L (stop and monitor monthly) 6
- Consider dose reduction when ferritin falls below 1000 μg/L at 2 consecutive visits, especially if dose >17.5 mg/kg/day 6
- Volume depletion occurs (vomiting, diarrhea, decreased oral intake) - resume only when renal function and hydration normalize 1, 6
Warning: Continued chelation when ferritin approaches normal range can result in life-threatening adverse events, particularly in pediatric patients 1, 6. Higher rates of renal adverse events occur with doses >17.5 mg/kg/day when ferritin <1000 μg/L 6.
High-Risk Populations Requiring Closer Monitoring
Elderly patients: Higher risk of serious and fatal adverse reactions; monitor more frequently 6
Pediatric patients: Fatal events reported in postmarketing surveillance, often associated with volume depletion or continued high-dose chelation when iron burden approaching normal 6
When NOT to Treat with Iron Removal
No phlebotomy or chelation is indicated when 2, 3:
- Elevated ferritin is due to inflammation, infection, malignancy, liver disease, metabolic syndrome, or alcohol use 4, 5, 2
- TSAT is normal or low, indicating no true iron overload 1
Referral to specialist (gastroenterologist, hematologist, or iron overload specialist) is appropriate when 2: