How to manage iron deficiency with low ferritin and elevated transferrin saturation?

Management of Low Ferritin with Elevated Transferrin Saturation

A patient with low ferritin (13) and elevated transferrin saturation (62%) should be evaluated for conditions that cause discordant iron parameters, particularly hemochromatosis, rather than iron deficiency.

Understanding the Paradoxical Iron Profile

This iron profile presents a diagnostic challenge due to the contradictory values:

• Ferritin of 13 μg/L: Well below the threshold of 30 μg/L that typically indicates depleted iron stores 1
• Transferrin saturation of 62%: Significantly elevated above the normal range (typically <45%)

Interpretation of These Values

1. Low ferritin (13 μg/L):

   • Serum ferritin is the most specific indicator of depleted iron stores 1
   • A value <15 μg/L has a sensitivity of 75% and specificity of 98% for iron deficiency 1

2. High transferrin saturation (62%):

   • Transferrin saturation >50% suggests iron overload rather than deficiency 1
   • This directly contradicts what would be expected in iron deficiency, where transferrin saturation is typically <16% 1

Differential Diagnosis

This discordant pattern suggests several possibilities:

1. Hereditary hemochromatosis: Most likely diagnosis - characterized by high transferrin saturation with variable ferritin levels (can be low early in disease)

2. Early iron overload with recent blood loss: Could explain the combination of high transferrin saturation with low ferritin

3. Laboratory error: Consider repeating tests to confirm findings

4. Mixed disorder: Underlying hemochromatosis with concurrent iron deficiency from blood loss

Recommended Diagnostic Approach

1. Confirm laboratory values:

   • Repeat serum ferritin and transferrin saturation tests
   • Ensure proper timing (morning sample, fasting) to minimize diurnal variation 1

2. Additional iron studies:

   • Complete blood count with RDW (elevated RDW >14% would support iron deficiency) 2
   • Serum iron and TIBC measurements

3. Genetic testing:

   • Test for HFE gene mutations (C282Y, H63D) to evaluate for hereditary hemochromatosis

4. Evaluate for sources of blood loss:

   • Gastrointestinal evaluation is mandatory in adult men and post-menopausal women with iron deficiency 2
   • Upper endoscopy and colonoscopy to rule out GI malignancy

5. Assess for inflammation:

   • Check CRP/ESR to evaluate for inflammatory conditions that might affect iron parameters

Treatment Considerations

Treatment should be directed at the underlying cause rather than empiric iron supplementation:

• If hemochromatosis is confirmed:

  • Therapeutic phlebotomy would be indicated
  • Avoid iron supplementation which could worsen iron overload

• If true iron deficiency with laboratory error is confirmed:

  • Oral iron therapy (100-200 mg elemental iron daily in divided doses) 2
  • Monitor response with repeat hemoglobin and iron studies in 4-8 weeks

• If mixed disorder:

  • Address the cause of blood loss
  • Treatment decisions should be guided by genetic testing results and overall clinical picture

Important Caveats

• Transferrin saturation can be falsely elevated due to hemolysis or timing of blood draw 1
• Serum ferritin can be falsely elevated in inflammatory conditions, but a value as low as 13 μg/L is unlikely to be falsely low 1
• The combination of low ferritin with high transferrin saturation is uncommon in simple iron deficiency and warrants thorough investigation 3
• Accepting iron deficiency as the diagnosis without investigating the underlying cause, particularly with these discordant values, could lead to missed diagnosis of a more serious condition 2