What treatment is recommended for a patient with iron overload, as indicated by high iron levels, low Unbound Iron-Binding Capacity (UIBC), and high iron saturation?

Management of Iron Overload

Therapeutic phlebotomy is the first-line treatment for iron overload, consisting of weekly removal of 450-500 mL of blood until serum ferritin reaches 50 μg/L, followed by maintenance phlebotomies every 1-4 months to maintain ferritin between 50-100 μg/L. 1

Diagnosis Confirmation

The laboratory values provided (low UIBC of 64, high iron of 244, and very high iron saturation of 79%) strongly indicate iron overload. These findings are characteristic of disorders with inappropriately low hepcidin concentration and disturbed plasma iron homeostasis 1.

Treatment Algorithm

First-Line Treatment: Phlebotomy

1. Initial Phase:

   • Remove 450-500 mL of blood weekly 1, 2
   • Monitor hemoglobin before each procedure 1
   • Check ferritin monthly or after every 4th phlebotomy 1
   • When ferritin falls below 200 μg/L, check after every 1-2 sessions 1
   • Continue until serum ferritin reaches 50 μg/L 1

2. Maintenance Phase:

   • Schedule phlebotomies every 1-4 months based on individual iron reaccumulation rate 1
   • Target serum ferritin: 50-100 μg/L 1
   • Monitor ferritin every 6 months to adjust treatment schedule 1

Second-Line Treatment: Chelation Therapy

Only when phlebotomy is not possible due to:

• Significant anemia
• Malignancy
• Hemodynamic instability 2

Options include:

• Deferasirox (oral): Most evidence in hemochromatosis but not FDA-approved for this indication 1

  • Caution: Can cause acute renal failure, hepatic injury, and GI hemorrhage 3
  • Contraindicated in patients with eGFR <40 mL/min/1.73m² 3
  • Requires baseline and regular monitoring of renal function, liver function, and auditory/ophthalmic examinations 3

• Deferoxamine (subcutaneous/intravenous): For transfusion-dependent patients 2

  • Highly specific iron chelator that binds to iron and facilitates excretion 2
  • Disadvantages: High cost, poor oral bioavailability, frequent administration 2

Monitoring

• Regular assessment:

  • Serum ferritin levels
  • Transferrin saturation
  • Complete blood count
  • Liver function tests
  • Glucose levels 1

• Organ-specific monitoring:

  • Cardiac function assessment
  • Liver imaging to track changes in hepatic iron concentration 1

Lifestyle Modifications

• Avoid iron supplementation and iron-fortified foods 1
• Limit vitamin C supplements, especially before iron depletion 1
• Restrict alcohol intake (complete abstinence if cirrhosis is present) 1
• Avoid raw or undercooked shellfish due to risk of Vibrio vulnificus infection 1

Potential Pitfalls

• Overtreatment: Reducing ferritin below 50 μg/L can increase dietary iron absorption and cause symptomatic iron deficiency 1
• Undertreatment: Continued organ damage due to inadequate iron removal 1
• Misdiagnosis: Elevated ferritin can be due to inflammation, not just iron overload 1
• Poor compliance: Patient adherence to phlebotomy regimens tends to decrease over time, with an average decline of 6.8% annually 4

Treatment Efficacy

Therapeutic phlebotomy has been shown to be highly effective, with studies demonstrating:

• Resolution of hyperferritinemia 5
• Prevention of complications when started before severe iron overload occurs 5
• Alleviation of symptoms including weakness, fatigue, increased hepatic enzymes, right upper quadrant pain, and hyperpigmentation 5
• Improvement in cardiac function when started early in the disease process 2

When properly implemented, this comprehensive approach can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity 5.