How is iron deficiency diagnosed and treated during acute infection when ferritin levels may be elevated due to inflammation?

From the Guidelines

Diagnosing iron deficiency during acute infection requires a comprehensive approach, considering alternative markers beyond ferritin, which can be falsely elevated due to inflammation, and treatment should prioritize intravenous iron supplementation, as it is more effective and better tolerated than oral iron, as recommended by the most recent guidelines 1.

Key Considerations

• Ferritin levels can be elevated during acute infection, making it a less reliable marker for iron deficiency.
• Transferrin saturation, soluble transferrin receptor, and reticulocyte hemoglobin content can provide more accurate assessments of iron status in the presence of inflammation.
• The ratio of soluble transferrin receptor to log ferritin can also help differentiate between iron deficiency and anemia of chronic disease.

Diagnostic Approach

• Measure transferrin saturation, with values below 20% suggesting iron deficiency.
• Assess soluble transferrin receptor levels, which increase with iron deficiency regardless of inflammation.
• Evaluate reticulocyte hemoglobin content, a direct indicator of iron availability for erythropoiesis.
• Consider hepcidin levels, which can help differentiate between iron deficiency and anemia of chronic disease.

Treatment Recommendations

• Intravenous iron supplementation is preferred over oral iron in cases of severe deficiency, malabsorption, or when rapid repletion is needed, with dosages such as iron sucrose 200mg or ferric carboxymaltose 500-1000mg 1.
• Oral iron supplementation, typically ferrous sulfate 325mg daily or twice daily, may be considered in mild cases, but absorption may be impaired during infection due to elevated hepcidin.
• Treatment should continue for 3-6 months after hemoglobin normalizes to replenish iron stores.
• Concurrent treatment of the underlying infection is crucial, as resolving inflammation will improve iron utilization and allow more accurate assessment of iron status with follow-up testing after the acute phase has resolved.

Monitoring and Follow-up

• Laboratory evaluation, including complete blood count and iron parameters, should be performed 4-8 weeks after the last infusion of intravenous iron.
• Ferritin levels should be monitored, with a goal of 50 ng/mL in the absence of inflammation, as recommended by recent guidelines 1.
• Regular follow-up is necessary to adjust treatment and monitor for potential complications, such as iron overload or anemia recurrence.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Diagnosing Iron Deficiency During Acute Infection

• Iron deficiency is often diagnosed through serum ferritin levels, but during acute infection, ferritin levels may be elevated due to inflammation, making diagnosis more complex 2.
• In patients with inflammatory conditions, a serum ferritin threshold of <100 μg/L or transferrin saturation (TSAT) < 20% can be considered diagnostic for iron deficiency 2.
• The standard threshold for iron deficiency (<30 μg/L) does not apply in inflammatory conditions, and TSAT should also be assessed to determine iron availability 2.

Treatment of Iron Deficiency During Acute Infection

• Ferric carboxymaltose is an effective option for treating iron-deficiency anemia in patients with inflammatory bowel disease, chronic kidney disease, and other conditions 3, 4.
• Intravenous administration of ferric carboxymaltose rapidly improves hemoglobin levels and replenishes depleted iron stores, with minimal risk of adverse events 3.
• Treatment with ferric carboxymaltose is well tolerated, with common adverse events including headache, dizziness, and nausea 3, 4.

Considerations for Iron Supplementation During Infection

• Iron overload can lead to impaired immunity and increased microbial virulence, making it essential to carefully consider iron supplementation during infection 5.
• In patients with tuberculosis, a serum ferritin cut-off value of ≤30 μg/L can be used to diagnose iron deficiency, but bone marrow examination is still the most reliable method 6.
• The predictive power of serum ferritin can be improved by combining it with other hematological and biochemical parameters, such as mean corpuscular volume, erythrocyte sedimentation rate, and total iron binding capacity 6.