What is the management plan for a patient with hemochromatosis and abnormal iron labs?

Management of Hemochromatosis with Abnormal Iron Labs

Patients with confirmed hemochromatosis and iron overload should undergo weekly therapeutic phlebotomy (500 mL) until serum ferritin reaches 50-100 μg/L, then continue maintenance phlebotomy lifelong to keep ferritin in this target range. 1

Initial Assessment Before Starting Phlebotomy

Before initiating treatment, obtain the following baseline studies:

• Serum ferritin level to quantify iron burden 1
• Transferrin saturation for baseline iron status 2
• Liver function tests (ALT, AST, bilirubin) to assess hepatic involvement 1
• Complete blood count to ensure adequate hemoglobin for phlebotomy 1
• Renal function (serum creatinine, eGFR) and urinalysis to establish baseline 1
• Auditory and ophthalmic examinations before starting therapy 1

Induction Phase: Iron Depletion Protocol

Phlebotomy Schedule and Monitoring

• Remove 500 mL of blood weekly or biweekly as the patient tolerates 1
• Check hemoglobin/hematocrit before each phlebotomy session to prevent excessive anemia 1
• Do not allow hemoglobin to fall more than 20% from baseline or below 12 g/dL 1, 3
• Monitor serum ferritin every 10-12 phlebotomies (approximately every 2-3 months) to track progress 1
• Continue weekly phlebotomy until ferritin reaches 50-100 μg/L, which is the target endpoint 1

Special Considerations for C282Y Homozygotes

• Patients with ferritin <1000 μg/L and normal liver enzymes can proceed directly to phlebotomy without liver biopsy 1
• Patients with ferritin ≥1000 μg/L or elevated transaminases may warrant additional evaluation for cirrhosis before initiating aggressive phlebotomy 1

Maintenance Phase: Preventing Iron Reaccumulation

Once iron depletion is achieved:

• Continue phlebotomy at individualized intervals (typically every 2-4 months) to maintain ferritin between 50-100 μg/L 1
• Monitor ferritin monthly initially, then adjust frequency based on stability 1
• If ferritin falls below 500 μg/L, interrupt phlebotomy and continue monthly monitoring 1
• Lifelong maintenance therapy is required to prevent iron reaccumulation 1

Research suggests that compliance with maintenance therapy declines approximately 6.8% annually, so regular follow-up is essential 4. Most patients require phlebotomy every 7.5 weeks on average to prevent reaccumulation 5.

Dietary and Supplement Modifications

• Avoid vitamin C supplements entirely, especially during active iron depletion, as vitamin C accelerates iron mobilization and can increase oxidative stress 1, 3
• Avoid iron supplements and iron-fortified foods 2
• Avoid raw shellfish due to risk of Vibrio vulnificus infection in iron-overloaded patients 1, 3
• No other dietary restrictions are necessary, as dietary iron restriction has minimal impact (only 2-4 mg/day) compared to phlebotomy (250 mg/week) 1

Alternative Treatment: Iron Chelation Therapy

For patients who cannot tolerate phlebotomy (severe anemia, cardiac dysfunction):

• Deferoxamine 20-40 mg/kg/day subcutaneously is the traditional chelation option 1
• Deferasirox (oral chelator) starting at 14 mg/kg/day for patients ≥2 years old with eGFR >60 mL/min/1.73 m² 6
• Monitor renal function, liver function, and blood counts monthly during chelation therapy due to significant toxicity risks 6
• Chelation is particularly indicated in secondary iron overload with ineffective erythropoiesis (e.g., thalassemia) where phlebotomy is not feasible 1

Critical Monitoring Parameters During Treatment

• Hemoglobin/hematocrit before each phlebotomy to prevent anemia 1
• Serum ferritin every 10-12 phlebotomies during induction, then monthly during maintenance 1
• Liver function tests periodically to assess for hepatic complications 1
• Auditory and ophthalmic testing every 12 months to detect rare complications 1, 6

Special Populations and Pitfalls

Patients with Advanced Cardiac Disease

• In patients with cardiomyopathy or arrhythmias, rapid iron mobilization increases risk of sudden death 1
• Consider slower phlebotomy schedule or iron chelation in patients with severe cardiac involvement 3, 7
• Cardiac MRI with T2 measurement can quantify myocardial iron burden* if cardiac hemochromatosis is suspected 3

Elderly Patients

• Monitor more frequently for toxicity as elderly patients have higher rates of serious adverse events 6
• Consider more relaxed ferritin targets during maintenance (up to 200 μg/L for women, 300 μg/L for men) 2

Pediatric Patients

• Interrupt phlebotomy during acute illnesses causing volume depletion (vomiting, diarrhea) 6
• Resume only when oral intake and volume status are normal 6
• Risk of overchelation is higher in children, particularly when ferritin <1000 μg/L and doses exceed 17.5 mg/kg/day 6

Avoiding Overchelation

• If ferritin falls below 1000 μg/L on two consecutive visits, consider dose reduction, especially if phlebotomy frequency is high 1
• Interrupt therapy if ferritin falls below 500 μg/L 1
• Continued aggressive iron removal when body iron is normal can cause life-threatening complications including renal failure and cytopenias 6

Patients with End-Organ Damage

• Patients with established cirrhosis, diabetes, arthropathy, or cardiomyopathy should still undergo phlebotomy to the same ferritin targets 1
• Cirrhosis is not reversed by iron removal, but phlebotomy prevents further progression 1
• Advanced decompensated cirrhosis is an indication for liver transplantation evaluation 1