How to manage a patient with iron overload indicated by a Transferrin Saturation (TSAT) of 90% and a low ferritin level of 29?

Management of Iron Overload with High TSAT (90%) and Low Ferritin (29)

This unusual pattern of high transferrin saturation (90%) with low ferritin (29) requires evaluation for hereditary hemochromatosis with concurrent iron deficiency, and therapeutic phlebotomy should be temporarily withheld until iron status normalizes.

Understanding the Paradoxical Iron Parameters

This combination of laboratory values presents a diagnostic challenge:

• TSAT of 90% suggests significant iron overload
• Ferritin of 29 ng/mL indicates iron deficiency

This paradoxical presentation likely represents one of two scenarios:

1. Hereditary hemochromatosis with excessive phlebotomy treatment
2. A rare form of hereditary hemochromatosis (such as TFR2-related type 3)

Diagnostic Approach

Initial Evaluation

• Confirm iron studies (repeat TSAT and ferritin)
• Check complete blood count for anemia
• Assess for symptoms of iron deficiency (fatigue, weakness, pallor)
• Evaluate for symptoms of iron overload (arthralgia, skin pigmentation)
• Review phlebotomy history if applicable

Additional Testing

• Genetic testing for hereditary hemochromatosis (HFE gene, TFR2 gene)
• Liver function tests to assess for hepatic damage
• Consider liver iron quantification (MRI or biopsy) if diagnosis remains unclear
• Measure hepcidin levels (likely to be inappropriately low)

Management Algorithm

1. If Patient Has Been Receiving Phlebotomy Therapy

• Temporarily discontinue phlebotomy until ferritin normalizes to at least 50-100 ng/mL 1
• Monitor hemoglobin and ferritin levels monthly
• Consider brief course of oral iron supplementation (ferrous sulfate 325 mg daily for 2-6 weeks) if symptomatic iron deficiency is present 2

2. If New Diagnosis of Hemochromatosis

• Defer initiation of phlebotomy until ferritin rises above minimum threshold
• Monitor iron parameters every 3 months
• Begin phlebotomy only when ferritin exceeds 200 ng/mL in women or 300 ng/mL in men 1, 3

3. Maintenance Therapy (After Ferritin Normalizes)

• Adjust phlebotomy frequency based on ferritin levels
• Target ferritin between 50-100 ng/mL 1
• Monitor hemoglobin before each phlebotomy
• Discontinue phlebotomy if hemoglobin falls below 11 g/dL 1

Important Considerations

Avoiding Excessive Iron Depletion

• Iron deficiency due to excessive phlebotomy can cause significant symptoms including fatigue, weakness, and reduced quality of life 2
• Recovery from iron deficiency without supplementation can take 8-24 months 2

Dietary Recommendations

• Avoid iron supplements and vitamin C supplements with meals
• Limit alcohol intake and red meat consumption
• Avoid iron-fortified foods 1

Monitoring Parameters

• Check hemoglobin before each phlebotomy
• Monitor ferritin every 3-6 months during maintenance phase
• Adjust phlebotomy frequency based on rate of iron reaccumulation 1

Special Considerations

• In rare forms of hemochromatosis (TFR2-related), patients may present with arthralgia at young ages despite variable ferritin levels 4
• Patients with transfusional iron overload may require different management approaches 5
• Consider specialist referral (hematology) for this unusual presentation of iron parameters 1