What is the treatment for elevated ferritin levels?

Treatment for Elevated Ferritin

The treatment for elevated ferritin depends critically on whether true iron overload exists (confirmed by elevated transferrin saturation >45%) versus inflammatory hyperferritinemia, with therapeutic phlebotomy being the mainstay for iron overload and chelation therapy reserved for patients who cannot tolerate phlebotomy or have transfusion-dependent conditions. 1

Initial Diagnostic Evaluation

Before initiating any treatment, you must distinguish true iron overload from other causes of hyperferritinemia:

• Measure transferrin saturation to differentiate iron overload (transferrin saturation >45%) from inflammatory causes, metabolic syndrome, malignancy, or infection 1, 2
• Obtain HFE genetic testing if transferrin saturation is elevated to diagnose hereditary hemochromatosis 1, 3
• Assess baseline organ function including duplicate serum creatinine measurements with eGFR calculation, liver function tests (ALT, AST, bilirubin), and urinalysis to evaluate renal tubular function 3, 4
• Perform baseline auditory and ophthalmic examinations before starting chelation therapy if phlebotomy is not an option 3, 4

Common pitfall: Hyperferritinemia is most frequently caused by malignancy, infection, or inflammation rather than true iron overload—in one large study, only 136 of 627 patients with ferritin >1000 μg/L had actual iron-overload syndromes 2

Treatment for True Iron Overload

Therapeutic Phlebotomy (First-Line Treatment)

For patients with iron overload and adequate hemoglobin, phlebotomy is the preferred treatment:

• Initiate weekly phlebotomy removing 400-500 mL of blood per session (each unit removes approximately 200-250 mg of iron) 5, 3
• Check hemoglobin/hematocrit before each session—postpone if hemoglobin <12 g/dL and discontinue if <11 g/dL 5, 3
• Monitor ferritin every 10-12 phlebotomies (approximately every 3 months initially), then more frequently as levels approach target 5, 3
• Continue until ferritin reaches 50-100 μg/L without inducing iron deficiency 5, 1, 3

For maintenance after achieving target:

• Perform phlebotomies every 3-6 months to maintain ferritin between 50-100 μg/L 1
• Monitor ferritin every 6 months during maintenance phase to ensure levels remain in target range 5

Iron Chelation Therapy (Alternative Treatment)

Chelation is indicated when phlebotomy is not feasible or in specific conditions:

Indications for Chelation:

• Transfusion-dependent patients with ferritin >1000 μg/L who have received ≥100 mL/kg of packed red blood cells (approximately 20 units for a 40 kg person) 4
• Myelodysplastic syndrome patients requiring ≥2 units/month for >1 year with ferritin >1000 μg/L 5
• Patients with anemia who cannot tolerate phlebotomy 5
• Patients undergoing allogeneic stem cell transplant to reduce procedure-related hepatic complications 5

Chelation Protocol:

Deferasirox (oral chelator):

• Starting dose: 14 mg/kg/day orally once daily on an empty stomach or with a light meal for patients ≥2 years old with eGFR >60 mL/min/1.73 m² 4
• Monitor ferritin monthly and adjust dose every 3-6 months in steps of 3.5-7 mg/kg based on trends 4
• Maximum dose: 28 mg/kg/day—doses above this are not recommended 4
• Interrupt therapy if ferritin falls below 500 μg/L and continue monthly monitoring 4
• Monitor renal function, liver function, and blood counts monthly due to potential toxicity 4

Special considerations for chelation:

• Avoid in severe hepatic impairment (Child-Pugh C) and reduce starting dose by 50% in moderate hepatic impairment (Child-Pugh B) 4
• Interrupt during acute illnesses causing volume depletion (vomiting, diarrhea) especially in pediatric and elderly patients 4
• Continue chelation as long as transfusion therapy continues and iron overload remains clinically relevant 5

Specific Disease Contexts

Ferroportin disease:

• Treat with repeated phlebotomies for both loss-of-function and gain-of-function mutations 5
• Extend phlebotomy intervals if anemia develops despite elevated ferritin 5
• Consider EPO therapy if anemia persists during phlebotomies 5

Aceruloplasminemia:

• Iron chelation therapy should be considered as anemia is typically mild and does not require treatment 5

Dietary and Lifestyle Modifications

These modifications are adjunctive and do not substitute for iron removal therapy:

• Avoid all iron supplements and iron-fortified foods including fortified breakfast cereals 5, 1, 3
• Limit vitamin C supplements to ≤500 mg/day as vitamin C enhances iron absorption 5, 1
• Restrict alcohol intake during iron depletion phase—patients with cirrhosis should completely abstain 5, 1
• Limit red meat consumption 5
• Avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection in iron-overloaded patients 5, 6, 1

Monitoring During Treatment

Regular monitoring is essential to avoid complications:

• Monitor serum ferritin monthly during initial therapy and every 3-6 months during maintenance 1, 3
• Check hemoglobin before each phlebotomy session 5, 3
• Perform liver function tests regularly during treatment 6
• Screen for hepatocellular carcinoma every 6 months in patients with cirrhosis, even after successful iron depletion 3

Critical pitfall: Serum ferritin should preferably not exceed 500 μg/L during intravenous iron supplementation to avoid toxicity, especially in children and adolescents 5

Expected Outcomes

• Survival improves to normal population levels when treatment is initiated before development of cirrhosis and diabetes 3
• Hepatic fibrosis reverses in approximately 30% of cases, though established cirrhosis does not reverse 3
• Cardiac function and diabetes control improve with successful iron depletion 3
• Elevated liver enzymes normalize with phlebotomy 3