What is the treatment plan for a patient with hyperferritinemia (elevated iron levels)?

Treatment of Elevated Iron Levels (Hyperferritinemia)

Therapeutic phlebotomy is the gold standard treatment for confirmed iron overload, initiated at 400-500 mL weekly until ferritin reaches 50-100 μg/L, with chelation therapy reserved for patients who cannot tolerate phlebotomy. 1, 2

Initial Diagnostic Assessment

Before initiating treatment, you must distinguish true iron overload from inflammatory hyperferritinemia:

• Measure transferrin saturation: Levels >45% indicate genuine iron overload requiring intervention 2
• Obtain baseline labs: Serum creatinine in duplicate, calculate eGFR, urinalysis, serum electrolytes, liver function tests (transaminases and bilirubin), and complete blood count 3
• Perform baseline auditory and ophthalmic examinations before starting any iron removal therapy 3

Primary Treatment: Therapeutic Phlebotomy

Initiation Phase

Begin weekly phlebotomy removing 400-500 mL of blood per session as the first-line treatment for patients with confirmed iron overload 1, 4, 2. This approach is supported by the European Association for the Study of the Liver and American Association for the Study of Liver Diseases guidelines.

• Check hemoglobin/hematocrit before each session 1, 2
• Postpone phlebotomy if hemoglobin falls below 12 g/dL 1, 2
• Discontinue phlebotomy if hemoglobin drops below 11 g/dL and reassess clinically 1
• Monitor serum ferritin monthly during initial therapy (or after every 4th phlebotomy) 1, 5
• When ferritin decreases below 200 μg/L, check ferritin every 1-2 sessions to avoid overchelation 1

Target Ferritin Levels

Continue phlebotomy until ferritin reaches 50-100 μg/L 1, 4, 5. The EASL guidelines recommend targeting 50 μg/L for the induction phase, though more relaxed targets of <200 μg/L for women and <300 μg/L for men may be tolerated during maintenance, particularly in elderly patients 1.

Maintenance Phase

After achieving target ferritin, continue maintenance phlebotomies every 1-4 months to keep ferritin between 50-100 μg/L 1, 4, 5. The frequency depends on individual iron accumulation rates, which average approximately 100 μg/L ferritin rise per year without treatment 1.

• Monitor serum ferritin every 6 months during maintenance 1, 5
• Adjust phlebotomy frequency based on ferritin trends 1

Alternative Treatment: Chelation Therapy

Chelation therapy is indicated when phlebotomy is contraindicated or not tolerated 1, 2. The American Journal of Hematology recommends chelation for:

• Patients with anemia, malignancy, or hemodynamic instability who cannot tolerate phlebotomy 2
• Transfusion-dependent patients with ferritin ≥1,000 ng/mL requiring ≥2 units/month for >1 year 1, 2
• Patients being considered for allogeneic stem cell transplant to reduce procedure-related hepatic complications and mortality 1, 2

Deferasirox Dosing (FDA-Approved Chelator)

Initiate deferasirox at 14 mg/kg/day orally once daily for patients ≥2 years old with eGFR >60 mL/min/1.73 m² and evidence of chronic transfusional iron overload (≥100 mL/kg packed RBCs transfused and ferritin consistently >1,000 mcg/L) 3.

• Adjust dose in steps of 3.5 or 7 mg/kg every 3-6 months based on ferritin trends 3
• Maximum dose is 28 mg/kg/day 3
• Monitor serum ferritin monthly to assess for overchelation 3
• Reduce dose if ferritin falls below 1,000 mcg/L at 2 consecutive visits, especially if dose >17.5 mg/kg/day 3
• Interrupt therapy if ferritin falls below 500 mcg/L and continue monthly monitoring 3

Critical Chelation Monitoring

Monitor renal function, liver function, and blood counts monthly during chelation therapy 3. Deferasirox carries significant risks:

• Interrupt therapy during volume depletion (vomiting, diarrhea, decreased oral intake) and resume only when renal function and fluid status normalize 3
• Discontinue immediately if severe skin reactions occur (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS) 3
• Perform auditory and ophthalmic testing every 12 months during treatment 3

Dietary and Lifestyle Modifications

Avoid all iron supplements and iron-fortified foods (including fortified breakfast cereals) 1, 4, 2, 5. This is a strong recommendation from multiple guideline societies.

• Limit vitamin C supplements to ≤500 mg/day as vitamin C enhances iron absorption 1, 2, 5
• Restrict alcohol intake during iron depletion phase; patients with cirrhosis should abstain completely 1, 5
• Limit red meat consumption 1
• Avoid raw shellfish due to risk of Vibrio vulnificus infection, particularly in patients with cirrhosis and iron overload 4, 5

Special Population Considerations

Myelodysplastic Syndrome (MDS) Patients

MDS patients most likely to benefit from iron overload management include: 1

• Transfusion-dependent patients requiring ≥2 units/month for >1 year
• Ferritin levels >1,000 ng/mL
• Low-risk MDS (IPSS low or intermediate-1; WHO RA, RARS, 5q-)
• Life expectancy ≥1 year
• Candidates for allograft

Continue chelation as long as transfusion therapy continues and iron overload remains clinically relevant 1, 2.

Elderly Patients

Monitor elderly patients more frequently for toxicity as they have higher rates of serious and fatal adverse reactions with both phlebotomy and chelation 3. More relaxed ferritin targets may be appropriate during maintenance phase 1.

Pediatric Patients

Interrupt therapy during acute illnesses causing volume depletion and monitor more frequently 3. Fatal adverse reactions have been reported in pediatric patients, often associated with continued high-dose chelation when iron burden approaches normal range 3.

Critical Pitfalls to Avoid

Overchelation is life-threatening: Continued administration of deferasirox at 14-28 mg/kg/day when body iron burden approaches normal range can result in fatal adverse events 3. Use the minimum effective dose once target ferritin is achieved.

Do not ignore transferrin saturation: Transferrin saturation may remain elevated (>50%) even when ferritin is within target range, and prolonged exposure may relate to persistent symptoms 1.

Avoid phlebotomy in patients with platelet counts <50 × 10⁹/L as deferasirox is contraindicated in this population 3.

Expected Outcomes

Phlebotomy improves survival to normal population levels when initiated before development of cirrhosis and diabetes 2. Additional benefits include:

• Reversal of hepatic fibrosis in approximately 30% of cases (though established cirrhosis does not reverse) 2
• Improvement in cardiac function and diabetes control 2
• Normalization of elevated liver enzymes 2
• Resolution of weakness, fatigue, right upper quadrant pain, and hyperpigmentation 6

Continue HCC screening every 6 months even after successful iron depletion in patients with cirrhosis, as HCC accounts for 30% of hemochromatosis-related deaths 2.