What are the treatment options for a patient with elevated iron ferritin levels?

Treatment of Elevated Ferritin Levels

The treatment approach for elevated ferritin depends critically on whether true iron overload exists (confirmed by transferrin saturation >45% and ferritin >1000 ng/mL), with therapeutic phlebotomy being first-line for hereditary hemochromatosis and iron chelation therapy reserved for transfusion-dependent patients or those unable to undergo phlebotomy. 1

Initial Diagnostic Assessment

Before initiating any treatment, you must distinguish true iron overload from inflammatory hyperferritinemia:

• Measure both ferritin AND transferrin saturation together - elevated ferritin alone is insufficient to diagnose iron overload 1
• Transferrin saturation >45% with ferritin >1000 ng/mL strongly suggests true iron overload, particularly hemochromatosis 1
• Exclude inflammatory causes by checking C-reactive protein, as inflammation falsely elevates ferritin despite actual iron deficiency 2
• Order HFE gene testing (C282Y and H63D mutations) when both ferritin and transferrin saturation are elevated 1

Treatment Algorithm by Clinical Scenario

Primary Iron Overload (Hereditary Hemochromatosis)

Therapeutic phlebotomy is the cornerstone of treatment for confirmed hemochromatosis 1, 3:

• Initial regimen: Remove one unit of blood (450-500 mL containing 200-250 mg iron) weekly 1
• Target ferritin level: 50-100 μg/L 1
• Maintenance therapy: Once target achieved, continue phlebotomy 3-4 times per year 1
• Monitor ferritin monthly during active treatment 1

Critical caveat: When ferritin exceeds 1000 μg/L with elevated transferrin saturation, significant risk of organ damage exists, particularly liver fibrosis 1. This makes prompt treatment essential for mortality and morbidity reduction.

Secondary Iron Overload (Transfusion-Dependent)

Iron chelation therapy should be initiated when specific criteria are met 4:

Initiation criteria (all must be considered):

• Ferritin levels ≥1,000 ng/mL 4
• Transfusion requirement ≥2 units/month for >1 year 4
• Life expectancy >1 year (iron complications take >1 year to manifest) 4
• Need to preserve organ function 4

Available chelation agents include deferoxamine, deferiprone, and deferasirox, with choice at physician discretion 4:

For deferasirox tablets specifically 5:

• Starting dose: 14 mg/kg/day orally once daily for patients ≥2 years with eGFR >60 mL/min/1.73 m² 5
• Dose adjustments: Make in steps of 3.5 or 7 mg/kg every 3-6 months based on ferritin trends 5
• Maximum dose: 28 mg/kg/day 5
• Target: Reduce ferritin to <1000 μg/L, then consider dose reduction 5
• Discontinue when ferritin falls below 500 μg/L 5

Duration of chelation: Continue as long as patient requires transfusion therapy and iron overload remains clinically relevant 4

Special Populations

Myelodysplastic Syndrome (MDS) patients most likely to benefit from chelation 4:

• Low-risk MDS (IPSS low or intermediate-1) 4
• WHO classification RA, RARS, or 5q- 4
• Transfusion-dependent requiring ≥2 units/month for >1 year 4
• No comorbidities limiting prognosis 4

Pre-transplant patients: Iron chelation prior to allogeneic stem cell transplant decreases hepatic complications and mortality, as ferritin >1000 ng/mL at transplant increases mortality risk 4, 6. Post-transplant, avoid chelation during immunosuppressive therapy due to overlapping renal toxicity; use phlebotomy instead when hemoglobin is stable 4

Chronic kidney disease patients: Intravenous iron may benefit patients with ferritin 500-1200 ng/mL and transferrin saturation <25% on erythropoietin therapy 1. However, withhold iron when ferritin exceeds 1000 ng/mL or transferrin saturation exceeds 50% 1

Monitoring During Treatment

• Ferritin levels: Monthly during active treatment 4, 5
• Renal function: Baseline and regular monitoring, especially with chelation therapy 5
• Liver function tests: Monitor transaminases and bilirubin 5
• Complete blood counts: Regular monitoring 5

Common Pitfalls to Avoid

Do not treat elevated ferritin without confirming iron overload - ferritin elevation occurs in malignancy (most common cause in one study), infection, inflammation, and liver disease 7. In these cases, treating the underlying condition is appropriate, not iron removal.

**Do not initiate chelation in patients with life expectancy <1 year** unless organ preservation is immediately warranted, as iron complications take >1 year to manifest 4

Do not continue iron supplementation when ferritin is normal or elevated - this is potentially harmful 2

Do not overlook family screening - first-degree relatives of hemochromatosis patients should undergo ferritin, transferrin saturation, and HFE genetic testing, as siblings have 25% chance of being affected 1, 3