What is the approach to managing elevated serum iron levels?

Approach to Elevated Serum Iron Levels

The first step in managing elevated serum iron is to determine whether the patient has hemochromatosis, as therapeutic phlebotomy is the mainstay of treatment for patients with confirmed hemochromatosis and evidence of iron overload. 1

Initial Assessment

When encountering elevated serum iron levels, a systematic diagnostic approach is essential:

1. Complete iron studies:

   • Serum ferritin
   • Transferrin saturation (TSAT)
   • Total iron binding capacity (TIBC)
   • Hemoglobin/hematocrit

2. Diagnostic thresholds:

   • Hemochromatosis is likely when TSAT >45% and serum ferritin is elevated
   • TSAT >50% is concerning for iron overload
   • Ferritin levels >300 ng/mL in men or >200 ng/mL in women warrant further investigation

3. Genetic testing:

   • HFE gene mutations (C282Y, H63D) if hemochromatosis is suspected

Management Based on Etiology

For Confirmed Hemochromatosis

1. Therapeutic phlebotomy:

   • Remove one unit of blood (450-500 mL, containing 200-250 mg iron) weekly or twice weekly as tolerated 2
   • Continue until ferritin reaches 50-100 μg/L 1
   • Monitor hemoglobin before each phlebotomy to avoid reducing it to <80% of starting value 2
   • Check ferritin after every 10-12 phlebotomies initially, then more frequently as target range is approached 2

2. Maintenance phase:

   • Individualized schedule based on rate of iron reaccumulation
   • Some patients require monthly phlebotomy while others need only 1-2 units removed per year 1
   • Regular monitoring of ferritin levels to maintain 50-100 μg/L 2

3. Special considerations:

   • Use more cautious phlebotomy schedule for patients with cardiac arrhythmias or cardiomyopathy 2
   • Patients with cirrhosis require continued screening for hepatocellular carcinoma even after iron depletion 1

For Non-Hemochromatosis Causes of Elevated Iron

1. Rule out false elevation:

   • Recent iron supplementation
   • Acute hepatitis
   • Hemolysis

2. Consider secondary causes:

   • Alcoholic liver disease
   • Hepatitis
   • Porphyria cutanea tarda
   • Multiple blood transfusions

Dietary and Lifestyle Modifications

For patients with confirmed iron overload:

1. Dietary restrictions:

   • Avoid iron supplements and iron-fortified foods
   • Limit red meat consumption
   • Restrict alcohol intake
   • Avoid vitamin C supplements >500 mg/day as they enhance iron absorption 1, 3
   • Consume fruit juices and citrus fruits in moderation 4

2. Avoid raw shellfish due to increased risk of infections in patients with iron overload 1

Monitoring and Follow-up

1. Regular laboratory monitoring:

   • Serum ferritin
   • Transferrin saturation
   • Liver function tests
   • Complete blood count

2. Screening for complications in patients with established iron overload:

   • Liver fibrosis/cirrhosis
   • Diabetes
   • Cardiac dysfunction
   • Arthropathy
   • Hypogonadism

Potential Pitfalls and Caveats

1. Avoid iron deficiency during treatment:

   • Never reduce ferritin below 50 μg/L 1
   • Monitor for symptoms of anemia during phlebotomy

2. Vitamin C considerations:

   • Patients with iron overload often become vitamin C deficient 2
   • Small doses of vitamin C (50-100 mg daily) may be given after initial month of treatment 5
   • Avoid high-dose vitamin C as it accelerates iron mobilization and may increase toxicity 3

3. Alternative treatments when phlebotomy is not possible:

   • Erythrocytapheresis for more efficient removal of red blood cells 1
   • Chelation therapy with deferoxamine (40-50 mg/kg/day) or deferasirox as second-line options 1, 5

4. Recognize that established cirrhosis will not reverse with iron removal, though portal hypertension may improve 2

By following this structured approach, elevated serum iron can be effectively diagnosed and managed, with the primary goal of preventing complications related to iron overload through appropriate iron removal strategies.