How are abnormal ferritin levels treated?

Treatment of Abnormal Ferritin Levels

Treatment of abnormal ferritin levels depends fundamentally on whether the patient has iron deficiency (low ferritin) or iron overload (high ferritin), with the underlying cause determining the specific therapeutic approach.

Low Ferritin: Iron Deficiency Treatment

Oral Iron Therapy

• Standard oral ferrous sulfate (300 mg three times daily) is the first-line treatment for iron deficiency anemia in adults, with serum ferritin remaining low until hemoglobin normalizes 1.
• Higher doses (600 mg three times daily) can cause temporary ferritin elevation within 2 days due to iron absorption exceeding erythropoietic utilization, but ferritin drops rapidly when iron is discontinued 1.
• Oral iron is generally preferred in non-urgent situations where gastrointestinal absorption is intact 2.

Intravenous Iron Therapy

For Cancer-Related Anemia:

• Patients with transferrin saturation (TSAT) between 20-50% and ferritin between 30-800 ng/mL can be offered IV iron with an erythropoiesis-stimulating agent (ESA) 2.
• IV iron monotherapy (without ESA) has limited evidence and cannot be routinely recommended for functional iron deficiency in cancer patients, though one study showed benefit in patients with ferritin <500 ng/mL 2.
• IV iron with ESA increases hemoglobin response rates by 10-30% and reduces red cell transfusions 2.

For Chronic Kidney Disease:

• Target ferritin >200 ng/mL and TSAT >20% for optimal anemia correction with lower erythropoietin doses 2.
• At ferritin 30 μg/L threshold, IV iron demonstrates 79% sensitivity and 98% specificity for treating iron deficiency 2.
• In dialysis patients with ferritin 500-1200 ng/mL and TSAT <25%, IV iron can increase hemoglobin faster than no iron (16±13 vs 11±14 g/L), though safety data are limited 2.
• Withhold iron when ferritin exceeds 1000 ng/mL or TSAT exceeds 50% 2.

Important Caveats:

• Single ferritin values should not guide treatment decisions in hemodialysis patients due to significant analytical variability (2-62% intraindividual variation) and interassay differences up to 150 ng/mL 3.
• Ferritin is an acute-phase reactant; a cancer patient with ferritin 60 ng/mL may actually have absolute iron deficiency despite the "normal" value 2.

High Ferritin: Iron Overload Treatment

HFE Hemochromatosis (Genetic)

Therapeutic Phlebotomy:

• Initiate phlebotomy when ferritin rises above the normal range 2.
• Monitor hemoglobin and hematocrit at each venesection; postpone if anemia develops 2.
• Target serum ferritin <50 μg/L during the depletion phase to achieve iron deficiency and normalize tissue iron 2.
• Measure ferritin every 3 months when levels are high, but increase frequency as ferritin approaches normal range 2.

Maintenance Therapy:

• Maintain ferritin at 50-100 μg/L with venesection every 3-6 months after achieving iron depletion 2.
• Alternative approach: cease venesection and monitor ferritin, restarting when it reaches the upper limit of normal 2.
• Patients with cirrhosis and diabetes have significantly reduced survival compared to those without these complications, emphasizing early treatment initiation 2.
• If ferritin <1000 μg/L with normal transaminases and no hepatomegaly, the risk of advanced liver fibrosis is very low 2.

Monitoring for Complications:

• Investigate unexpected slow iron reaccumulation for gastrointestinal blood loss (peptic ulcers, colonic disease) or hematuria, especially in elderly patients 2.
• Proton pump inhibitors reduce iron absorption and venesection requirements 2.

Dietary Considerations:

• Avoid iron-containing vitamin preparations and iron-supplemented foods (breakfast cereals) 2.
• Limit vitamin C supplements to ≤500 mg/day due to potential cardiac toxicity in iron overload 2.
• Avoid excess alcohol as it increases hepatic damage in hemochromatosis 2.
• No conclusive evidence supports dietary iron restriction as beneficial beyond these measures 2.

Transfusional Iron Overload

Deferasirox (Iron Chelation):

• Initiate therapy only when patients have received ≥100 mL/kg packed red blood cells (≥20 units for 40 kg person) AND ferritin consistently >1000 mcg/L 4.
• Starting dose: 14 mg/kg/day orally once daily for patients ≥2 years with eGFR >60 mL/min/1.73 m² 4.
• Adjust dose in 3.5 or 7 mg/kg increments every 3-6 months based on ferritin trends 4.
• Maximum dose: 28 mg/kg/day 4.

Monitoring During Chelation:

• Measure ferritin monthly and adjust dose to achieve decreasing trends 4.
• If ferritin falls below 1000 mcg/L at 2 consecutive visits, consider dose reduction, especially if dose >17.5 mg/kg/day 4.
• If ferritin falls below 500 mcg/L, interrupt therapy and continue monthly monitoring 4.
• Monitor renal function, liver function, and blood counts monthly 4.
• Interrupt therapy during acute illnesses causing volume depletion (vomiting, diarrhea) 4.

Overchelation Prevention:

• Continued administration at 14-28 mg/kg/day when iron burden approaches normal range can cause life-threatening adverse events 4.
• Use minimum effective dose to maintain iron burden in target range 4.

Acute Hepatic Porphyrias (Hemin-Induced Iron Overload)

• Measure serum ferritin every 3-6 months or after every ~12 doses of prophylactic hemin 2.
• Begin therapeutic phlebotomy when ferritin >1000 ng/mL (or earlier) with goal ferritin ~150 ng/mL 2.
• Frequent small-volume phlebotomies may be necessary in patients with indwelling venous ports due to limited access 2.

Prognostic Implications

• Even "normal" ferritin concentrations (78-220 ng/mL) in hospitalized patients are independently associated with increased 30-day mortality (OR 2.05) and long-term mortality (HR 1.54) when measured at admission 5.
• Low-grade ferritinemia in the context of inflammation may not be benign and warrants clinical attention 5.
• Ferritin >2000 ng/mL is associated with hematological diseases (45.9%), liver diseases (23%), chronic renal failure (17.8%), and neoplastic diseases (10.4%) 6.
• Adult-onset Still's disease shows extremely elevated ferritin (mean 11,322 ng/mL), making it a useful diagnostic marker 6.