What are the treatment options for abnormal ferritin levels?

Treatment of Abnormal Ferritin Levels

Low Ferritin (Iron Deficiency)

All patients with iron deficiency should receive oral iron supplementation as first-line therapy, with ferrous sulfate 200 mg three times daily being the most cost-effective option, continued for 3 months after anemia correction to replenish iron stores. 1

Initial Treatment Approach

• Start with oral iron therapy using ferrous sulfate 200 mg three times daily, or alternatively ferrous gluconate or ferrous fumarate, which are equally effective 1
• Liquid preparations may be better tolerated when tablets cause side effects 1
• Continue treatment for 8-10 weeks initially, then monitor response with repeat ferritin and hemoglobin measurements, targeting ferritin ≥50 μg/L in the absence of inflammation 2
• After achieving normal hemoglobin, continue iron supplementation for an additional 3 months to fully replenish body iron stores 1

Optimizing Oral Iron Absorption

• Add ascorbic acid (vitamin C) to enhance iron absorption, particularly when response is poor 1
• Avoid iron absorption inhibitors including tea, coffee, and calcium-containing products 2
• Limit alcohol intake, especially if liver enzymes are elevated 2

Monitoring Response

• Expect hemoglobin to rise by 2 g/dL after 3-4 weeks of treatment 1
• Failure to achieve this response typically indicates poor compliance, misdiagnosis, continued blood loss, or malabsorption 1
• Monitor hemoglobin and red cell indices every 3 months for one year, then again after an additional year 1
• Measure ferritin at follow-up visits; if levels fall below normal, resume oral iron supplementation 1

When to Use Intravenous Iron

Consider intravenous iron when oral therapy fails, in malabsorption disorders, or when rapid iron repletion is needed. 2

• Specific indications include: intolerance to at least two oral iron preparations, documented non-compliance, malabsorption syndromes, or need for rapid repletion 1, 2
• Available IV formulations include iron dextran, ferric carboxymaltose, and ferric derisomaltose 2
• Avoid measuring iron parameters within 4 weeks of IV iron administration as it interferes with test results 2
• Be aware that IV iron carries risks including infusion reactions (occurring in approximately 4.3% of patients) and is considerably more expensive than oral therapy 1

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Elevated Ferritin (Iron Overload)

Transfusional Iron Overload

Initiate iron chelation therapy when serum ferritin reaches 1000 ng/mL in transfusion-dependent patients, or when transfusion requirement is ≥2 units/month for more than one year. 1

Criteria for Starting Chelation

• Evidence of chronic transfusional iron overload: at least 100 mL/kg of packed red blood cells transfused (approximately 20 units for a 40 kg person) 3
• Serum ferritin consistently >1000 ng/mL 1, 3
• Transfusion rate of 2 units/month or more persisting for greater than one year 1
• Need to preserve organ function to maintain quality of life 1

Deferasirox Dosing and Monitoring

• Initial dose: 14 mg/kg body weight orally once daily for patients ≥2 years old with eGFR >60 mL/min/1.73 m² 3
• Take on empty stomach or with light meal (containing <7% fat content and approximately 250 calories) 3
• Monitor serum ferritin monthly and adjust dose every 3-6 months based on ferritin trends 3
• Adjust dose in steps of 3.5 or 7 mg/kg to achieve decreasing ferritin trend 3
• Maximum dose is 28 mg/kg; doses above this are not recommended 3

Critical Monitoring Parameters

Before starting and during chelation therapy, evaluate:

• Serum ferritin monthly to assess for overchelation 3
• Renal function (serum creatinine in duplicate, eGFR, urinalysis, serum electrolytes) 3
• Liver function (serum transaminases and bilirubin) 3
• Complete blood counts 3
• Baseline and periodic (every 12 months) auditory and ophthalmic examinations 3

Dose Adjustments Based on Ferritin Response

• If ferritin falls below 1000 ng/mL at 2 consecutive visits: consider dose reduction, especially if dose is >17.5 mg/kg/day 3
• If ferritin falls below 500 ng/mL: interrupt chelation therapy and continue monthly monitoring 3
• For patients no longer requiring regular transfusions, evaluate the need for ongoing chelation 3

Special Populations Requiring Chelation

• Patients with myelodysplastic syndromes (MDS) with low or intermediate IPSS score and transfusion-dependent anemia 1
• Patients with idiopathic myelofibrosis with favorable or intermediate prognosis 1
• Patients undergoing allogeneic stem cell transplant should receive chelation if ferritin >1000 ng/mL, as this decreases procedure-related hepatic complications and mortality 1

Prophylactic Hemin-Related Iron Overload

In patients receiving frequent prophylactic hemin infusions (for acute hepatic porphyrias), measure serum ferritin every 3-6 months or after every ~12 doses, and begin therapeutic phlebotomy when ferritin exceeds 1000 ng/mL. 1

• Hemin contains 9% iron by weight and can lead to iron overload with repeated administration 1
• Measure ferritin between attacks and before the next hemin dose to avoid acute phase effects 1
• Target ferritin goal of ~150 ng/mL with phlebotomy 1
• Frequent small-volume phlebotomies may be more feasible in patients with limited venous access 1

Elevated Ferritin in Dialysis Patients

In hemodialysis patients with ferritin 500-1200 ng/mL and transferrin saturation <25%, intravenous iron can increase hemoglobin and reduce ESA requirements, though safety data are limited. 1

• The DRIVE study demonstrated that IV ferric gluconate 125 mg over 8 consecutive hemodialysis sessions increased hemoglobin significantly more than no iron (16±13 vs 11±14 g/L) in patients on stable high-dose erythropoietin 1
• Baseline ferritin was not predictive of iron responsiveness 1
• Balance potential hemoglobin increase against perceived infection and cardiovascular risk when considering ongoing iron in patients with ferritin >800 ng/mL 1
• Major safety concerns include infusion reactions and theoretical iron overload, though organ damage typically requires >20 g excess iron 1

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Differential Diagnosis of Markedly Elevated Ferritin

When ferritin is markedly elevated (>1000 μg/L) without clear transfusional iron overload:

• Most common causes are malignancy (24%) and iron-overload syndromes (22%) in a tertiary care setting 4
• Inflammatory rheumatologic conditions (adult-onset Still's disease, systemic juvenile idiopathic arthritis, hemophagocytic lymphohistiocytosis) are rare but have extremely high ferritin levels (average 14,242 μg/L) 4
• In critically ill patients, ferritin >9,083 μg/L has 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis 5
• Other causes include severe infections, hepatitis, malaria, and inflammatory conditions 4, 5
• Ferritin is an acute phase reactant and increases nonspecifically in inflammatory and malignant diseases 6, 7

Key Safety Warnings

• Interrupt chelation therapy in patients with volume depletion (vomiting, diarrhea, decreased oral intake) and resume only when renal function and volume status normalize 3
• Continued chelation at 14-28 mg/kg/day when iron burden approaches normal range can result in life-threatening adverse events 3
• Elderly patients require more frequent monitoring for toxicity with deferasirox 3
• Deferasirox is contraindicated with platelet counts <50 x 10⁹/L 3