What are the treatment options for elevated ferritin levels?

Treatment of Elevated Ferritin Levels

The treatment of elevated ferritin depends entirely on whether true iron overload is present or if ferritin elevation is reactive—in the vast majority of cases (90%), elevated ferritin reflects inflammation, malignancy, or metabolic conditions rather than iron overload, and these patients should NOT receive iron removal therapy. 1, 2

Initial Assessment: Distinguish Iron Overload from Reactive Hyperferritinemia

Step 1: Determine the Underlying Cause

• Only 10% of elevated ferritin cases represent true iron overload requiring therapeutic intervention; the remaining 90% are due to acute phase reactions, inflammation, malignancy, infection, liver disease, metabolic syndrome, or alcohol use 1, 2

• Malignancy is the most common cause of markedly elevated ferritin (>1000 μg/L), followed by iron overload syndromes 3

• Measure transferrin saturation (TSAT) alongside ferritin to differentiate iron overload from inflammatory states:

  • TSAT >45-50% suggests true iron overload 4
  • TSAT <20% with elevated ferritin indicates functional iron deficiency or inflammation 4

Step 2: Identify Specific Conditions

• Screen for hereditary hemochromatosis (HFE) with genetic testing if TSAT is elevated and clinical suspicion exists 4, 1

• Evaluate for secondary causes: alcohol consumption, metabolic syndrome, obesity, diabetes, liver disease, chronic kidney disease, malignancy, infection, or inflammatory conditions 1, 2

• Consider referral to gastroenterology, hematology, or iron overload specialist if ferritin >1000 μg/L or cause remains unclear 1

Treatment Based on Etiology

For TRUE Iron Overload (HFE Hemochromatosis, Transfusional Iron Overload)

Therapeutic Phlebotomy

• Phlebotomy is the primary treatment for HFE hemochromatosis and should be initiated when ferritin is above the normal range 4

• Target serum ferritin <50 μg/L during the depletion phase to achieve iron deficiency and normalize tissue iron 4

• Maintenance therapy: After depletion, maintain ferritin at 50-100 μg/L with phlebotomy every 3-6 months 4

• Monitor hemoglobin and hematocrit at each phlebotomy session; postpone if anemia develops 4

• For ferroportin disease (both loss-of-function and gain-of-function mutations), treat with repeated phlebotomies; extend intervals if anemia develops despite elevated ferritin 4

Iron Chelation Therapy

For transfusional iron overload (myelodysplastic syndromes, thalassemia, chronic transfusion-dependent anemias):

• Initiate chelation when serum ferritin reaches ≥1000 μg/L in patients requiring ≥2 units/month for >1 year, or when organ preservation is needed 4

• Deferasirox (oral chelator) is the primary agent:

  • Starting dose: 14 mg/kg/day for patients with eGFR >60 mL/min/1.73 m² 5
  • Adjust dose every 3-6 months based on ferritin trends in increments of 3.5-7 mg/kg 5
  • Maximum dose: 28 mg/kg/day 5
  • Monitor serum ferritin monthly and adjust to achieve decreasing trends 5

• Target ferritin levels during chelation:

  • Reduce dose if ferritin falls below 1000 μg/L on 2 consecutive visits, especially if dose >17.5 mg/kg/day 5
  • Interrupt therapy if ferritin falls below 500 μg/L to avoid overchelation 5

• Continue chelation as long as transfusion therapy continues and iron overload remains clinically relevant 4

• Monitor for toxicity: Check renal function (serum creatinine, eGFR, urinalysis), liver function (transaminases, bilirubin), and blood counts monthly 5

For Chronic Kidney Disease with Elevated Ferritin

• Do NOT withhold IV iron solely based on elevated ferritin if TSAT is low (<25%) and patient is on erythropoiesis-stimulating agents (ESAs) with inadequate hemoglobin response 4

• Maintain TSAT >20% and ferritin >200 ng/mL in hemodialysis patients receiving ESAs to optimize anemia correction and reduce ESA requirements 4

• Upper safety limits: Temporarily withhold IV iron if TSAT chronically >50% or ferritin >800-1000 ng/mL 4

• Monitor ferritin every 3 months minimum, monthly if possible, in transfusion-dependent patients 4

For Reactive Hyperferritinemia (No Iron Overload)

• Treat the underlying condition (infection, inflammation, malignancy, liver disease, metabolic syndrome) rather than the ferritin elevation itself 1, 2

• Avoid phlebotomy and iron chelation in patients without true iron overload, as these interventions provide no benefit and may cause harm 1, 2

• Monitor ferritin levels to track response to treatment of the underlying condition 1, 2

Critical Safety Considerations

• Avoid overchelation: Continued chelation when ferritin approaches normal range (especially with doses 14-28 mg/kg/day deferasirox) can result in life-threatening adverse events 5

• Pediatric and elderly patients require closer monitoring due to increased risk of serious and fatal adverse reactions with iron chelation 5

• Interrupt chelation during volume depletion (vomiting, diarrhea, decreased oral intake) and resume only when renal function and hydration normalize 5

• In children and adolescents receiving IV iron, serum ferritin should preferably not exceed 500 mg/L to avoid toxicity 4