What is the appropriate management for a patient with iron overload?

Management of Iron Overload Based on Laboratory Values

For a patient with severe iron overload (transferrin saturation 93%, elevated iron, low UIBC), therapeutic phlebotomy should be initiated immediately as the primary treatment to reduce iron stores and prevent organ damage.

Assessment of Iron Overload Severity

The laboratory values indicate severe iron overload:

• Ferritin: 43 (normal/low)
• Iron: 337 (high)
• TIBC: 362 (normal)
• UIBC: 25 (low)
• Transferrin: 304 (normal)
• Transferrin % Saturation: 93% (severely elevated)

These values show a pattern of iron overload with extremely high transferrin saturation, which is concerning for potential organ damage despite the relatively normal ferritin level.

Diagnostic Workup

1. Genetic testing:

   • Test for HFE gene mutations (C282Y and H63D) to determine if hereditary hemochromatosis is present 1
   • If genetic testing is negative for C282Y homozygosity or C282Y/H63D compound heterozygosity, investigate for secondary causes 1, 2

2. Imaging:

   • MRI to quantify hepatic iron concentration and assess extrahepatic organ involvement 1
   • Consider cardiac MRI if signs of heart disease are present 1, 3

3. Organ function assessment:

   • Liver function tests (ALT, AST)
   • Cardiac evaluation (ECG, echocardiogram)
   • Endocrine function tests (glucose, thyroid function)

Treatment Algorithm

Primary Treatment: Therapeutic Phlebotomy

• Initial phase: Weekly phlebotomy (removal of 450-500 mL of blood) 1, 4
• Target: Reduce serum ferritin to 50-100 μg/L 1
• Monitoring: Check hematocrit before each phlebotomy session and ferritin every 10-12 phlebotomies 4

For Patients Unable to Tolerate Phlebotomy

Consider iron chelation therapy:

• Deferasirox (oral): For transfusional iron overload in patients ≥2 years old 5
  • Caution: Monitor renal and hepatic function; avoid in pregnancy
• Deferoxamine (parenteral): For severe iron overload 6
  • Administer by slow subcutaneous or IV infusion to avoid hypotension and shock
  • Monitor for potential infections, especially Yersinia

Monitoring and Follow-up

• Monitor serum ferritin and transferrin saturation every 3 months during treatment 1
• Once target ferritin is reached, transition to maintenance phlebotomy (typically every 2-4 months) 1
• Annual assessment of organ function (liver, heart, endocrine) 1, 4

Lifestyle Modifications

• Avoid vitamin C supplements during active iron reduction (can increase iron toxicity) 1
• Avoid iron supplements and raw shellfish (risk of Vibrio vulnificus infection) 1
• Limit alcohol consumption 4
• Regular physical activity 4

Special Considerations

• If cirrhosis is present, phlebotomy will not reverse advanced liver disease 1
• For secondary iron overload (e.g., from transfusions), the underlying cause should be addressed while treating iron overload 7, 8
• In patients with cardiac involvement, more aggressive therapy may be needed as iron-overload cardiomyopathy is potentially reversible if treated early 3

Pitfalls to Avoid

1. Don't rely solely on ferritin: In this case, ferritin is not elevated despite severe iron overload as indicated by transferrin saturation. Transferrin saturation >45% is more sensitive for early iron overload detection 1

2. Don't delay treatment: High transferrin saturation (>90%) indicates severe iron overload that requires immediate intervention to prevent organ damage 1

3. Don't use aggressive phlebotomy in patients with anemia, cardiac compromise, or hypoproteinemia

4. Don't miss secondary causes of iron overload if genetic testing is negative for hereditary hemochromatosis 2, 7