What is the treatment for high iron levels with elevated ferritin levels?

Treatment of High Iron and Elevated Ferritin Levels

Initiate weekly therapeutic phlebotomy (removal of 400-500 mL of blood) as the primary treatment for iron overload with elevated ferritin, continuing until ferritin reaches 50-100 μg/L. 1

Initial Diagnostic Confirmation

Before starting treatment, confirm true iron overload versus inflammatory hyperferritinemia:

• Measure transferrin saturation - elevated levels >45% indicate genuine iron overload rather than inflammation-related ferritin elevation 2
• Order HFE genetic testing if transferrin saturation is elevated to diagnose hereditary hemochromatosis 2
• Obtain baseline liver function tests (ALT, AST, bilirubin) and consider liver biopsy if ferritin >1000 μg/L with elevated transaminases and platelets <200,000, which predicts cirrhosis in 80% of cases 2
• Check baseline auditory and ophthalmic examinations before starting therapy 2

Therapeutic Phlebotomy Protocol

Primary treatment approach:

• Remove 400-500 mL of blood weekly (or twice weekly if tolerated), with each unit containing approximately 200-250 mg of iron 1, 2
• Check hemoglobin/hematocrit before each session - postpone phlebotomy if hemoglobin falls below 12 g/dL and discontinue if <11 g/dL until anemia resolves 1, 2
• Monitor ferritin every 10-12 phlebotomies (approximately every 3 months) initially, then more frequently as levels approach target 1, 2
• Continue phlebotomy until ferritin reaches 50-100 μg/L without inducing iron deficiency 1, 2

Critical safety thresholds:

• Interrupt therapy completely if ferritin falls below 500 μg/L with continued monthly monitoring 2
• Interrupt phlebotomy during acute illnesses causing volume depletion, particularly in pediatric and elderly patients 2

Maintenance Therapy

After achieving target ferritin levels:

• Continue maintenance phlebotomies every 3-6 months to maintain ferritin between 50-100 μg/L 1, 3
• Monitor serum ferritin monthly during maintenance phase to avoid iron overload or excessive chelation 3
• Alternative approach: cease phlebotomy and monitor ferritin, restarting when it reaches upper limit of normal (though this has lower evidence quality) 1

Dietary and Lifestyle Modifications

• Avoid all iron supplements and iron-fortified foods including fortified breakfast cereals 1, 2
• Limit vitamin C supplements to ≤500 mg/day as vitamin C enhances iron absorption 1, 2
• Restrict or eliminate alcohol consumption during iron depletion phase; patients with cirrhosis must completely abstain 1, 2
• Avoid raw shellfish if cirrhosis is present due to Vibrio vulnificus infection risk 1, 3
• Maintain a broadly healthy diet rather than strict iron restriction 1

Alternative Treatment: Iron Chelation Therapy

Chelation therapy with deferasirox is reserved for specific situations:

• Patients with anemia who cannot tolerate phlebotomy 4
• Patients with severe congestive heart failure 4
• Patients unable to undergo phlebotomy for other medical reasons

Deferasirox dosing: 5-30 mg/kg/day based on baseline liver iron concentration, taken once daily on an empty stomach or with a light meal 5

Critical monitoring for deferasirox:

• Monitor renal function, liver function, and blood counts regularly due to risks of renal toxicity, hepatotoxicity, and bone marrow suppression 5
• Interrupt treatment if cytopenias develop 5
• Elderly patients require more frequent monitoring for toxicity 5

Special Populations and Monitoring

Patients with cirrhosis:

• Continue hepatocellular carcinoma (HCC) screening every 6 months even after successful iron depletion, as HCC accounts for 30% of hemochromatosis-related deaths 2
• Phlebotomy improves survival only if initiated before cirrhosis develops 2
• Portal hypertension may improve with treatment 2

Pediatric and elderly patients:

• Require more frequent monitoring during volume depletion 2
• Higher risk of serious adverse events, particularly when continuing treatment as iron burden approaches normal range 5

Expected Outcomes and Prognosis

• Survival improves to normal population levels if treatment begins before development of cirrhosis and diabetes 1, 2
• Hepatic fibrosis reverses in approximately 30% of cases, though established cirrhosis does not reverse 2
• Cardiac function and diabetes control improve with phlebotomy 2
• Elevated liver enzymes normalize with successful iron depletion 2

Critical Pitfalls to Avoid

• Do not continue aggressive phlebotomy (doses equivalent to 14-28 mg/kg/day deferasirox) when body iron burden approaches normal range, as this can result in life-threatening adverse events 5
• Do not overlook volume depletion - interrupt treatment and resume only when renal function and fluid volume normalize 2
• Monitor more frequently when ferritin falls below 1000 μg/L and consider dose reduction, especially if phlebotomy frequency is high 2
• Avoid overchelation by careful monitoring of ferritin levels 1