How to manage a patient with hyperferremia?

Management of Hyperferremia

Therapeutic phlebotomy is the first-line treatment for a patient with elevated serum iron (219 μg/dL) and normal ferritin (30 ng/mL), with a goal of maintaining ferritin between 50-100 ng/mL to prevent complications. 1

Initial Assessment

This patient presents with:

• Elevated serum iron: 219 μg/dL (reference range: 59-158 μg/dL)
• Normal ferritin: 30 ng/mL (reference range: 30-400 ng/mL)
• High-normal transferrin saturation: 51% (reference range: 20-55%)
• Normal TIBC: 427 μg/dL (reference range: 228-428 μg/dL)

Differential Diagnosis

1. Early hemochromatosis: Elevated serum iron with transferrin saturation at upper limit of normal
2. Acute iron ingestion: From supplements or medications
3. Hemolysis: Can cause transient hyperferremia
4. Liver disease: Can alter iron parameters

Treatment Approach

First-line Treatment: Therapeutic Phlebotomy

• Initial phase: Weekly phlebotomy of 450-500 mL of blood 1

  • Each unit removes approximately 200-250 mg of iron 2
  • Monitor hemoglobin/hematocrit before each phlebotomy to avoid reducing to <80% of starting value 2

• Monitoring during initial phase:

  • Check ferritin monthly during initial treatment 1
  • Monitor liver enzymes every 3 months 1
  • Transferrin saturation typically remains elevated until iron stores are depleted 2

• Target: Ferritin level between 50-100 ng/mL 2, 1

  • Avoid reducing ferritin below 50 ng/mL to prevent iron deficiency 1

• Maintenance phase: Once target ferritin is achieved, transition to maintenance phlebotomy every 1-4 months based on individual iron reaccumulation rate 1

Alternative Treatment (if phlebotomy contraindicated)

For patients with anemia, hemodynamic instability, or other contraindications to phlebotomy:

• Iron chelation therapy with deferasirox may be considered 1, 3
  • Dosing must be adjusted based on renal function
  • Contraindicated in patients with eGFR <40 mL/min/1.73m² 3
  • Monitor for adverse effects:
    • Renal toxicity: Monitor eGFR weekly for first month, then monthly 3
    • Hepatic toxicity: Check transaminases and bilirubin every 2 weeks initially, then monthly 3
    • GI ulceration: Monitor for signs/symptoms of GI bleeding 3

Lifestyle Modifications

• Dietary changes:

  • Avoid iron supplements and iron-fortified foods 1
  • Limit red meat consumption 1
  • Avoid supplemental vitamin C, especially before meals (increases iron absorption) 1

• Alcohol restriction:

  • Limit alcohol intake during iron depletion phase 1
  • Complete abstinence if liver enzymes are elevated or cirrhosis is present 1

Monitoring and Follow-up

• During initial treatment:

  • Ferritin levels: Monthly until target achieved 1
  • Transferrin saturation and serum iron: Monthly 1
  • Complete blood count: Before each phlebotomy 2, 1
  • Liver function tests: Every 3 months 1

• During maintenance phase:

  • Ferritin levels: Every 6 months 1
  • Adjust phlebotomy frequency based on ferritin trends 1

Special Considerations

• Genetic testing: Consider HFE mutation testing (C282Y, H63D) if hereditary hemochromatosis is suspected 1

• Organ-specific monitoring: If iron overload is confirmed and persistent, consider:

  • Liver MRI if ferritin remains >1000 μg/L or liver enzymes remain elevated 1
  • Cardiac function assessment if evidence of cardiomyopathy 1

Common Pitfalls to Avoid

1. Overtreatment: Reducing ferritin below 50 ng/mL can increase dietary iron absorption and cause symptomatic iron deficiency 1

2. Undertreatment: Inadequate iron removal can lead to continued organ damage 1

3. Misinterpreting laboratory values: TIBC measurements can be unreliable in acute iron elevation scenarios 4

4. Overlooking underlying causes: Investigate for hereditary hemochromatosis, liver disease, or other causes of iron dysregulation 1, 5

5. Ignoring renal function: When using chelation therapy, renal function must be closely monitored as deferasirox can cause acute kidney injury 3