How do you interpret and manage abnormal iron panel and ferritin results?

Interpreting Iron Panel and Ferritin

Interpret ferritin in the context of inflammation: use <45 ng/mL for iron deficiency anemia diagnosis, but raise the threshold to <100 ng/mL when inflammation is present (elevated CRP/ESR), and combine with transferrin saturation <16-20% to distinguish iron deficiency from anemia of chronic disease. 1

Diagnostic Thresholds for Iron Deficiency

Without Inflammation

• Ferritin <45 ng/mL confirms iron deficiency anemia when hemoglobin is <13 g/dL (men) or <12 g/dL (non-pregnant women) 1
• Ferritin <15 ng/mL indicates absolute iron deficiency in the absence of inflammatory markers 1
• Transferrin saturation <16% is sensitive for iron deficiency but has low specificity (40-50%) 1

With Inflammation Present

Ferritin is an acute phase reactant that rises during inflammation, masking true iron deficiency. When CRP or ESR are elevated:

• Ferritin <30 ng/mL still indicates likely iron deficiency 1
• Ferritin 30-100 ng/mL with transferrin saturation <16% suggests iron deficiency despite inflammation 1
• Ferritin >100 ng/mL with transferrin saturation <16% indicates anemia of chronic disease 1

Critical pitfall: A "normal" ferritin of 50-100 ng/mL in an inflamed patient may still represent iron deficiency. Always check inflammatory markers (CRP, ESR) when interpreting ferritin. 1

Distinguishing Iron Deficiency from Anemia of Chronic Disease

Use this algorithmic approach when transferrin saturation and ferritin are discordant:

• Low transferrin saturation (<20%) + High ferritin (>300 ng/mL) = anemia of inflammation 1
• Low transferrin saturation (<16%) + Low-normal ferritin (30-100 ng/mL) + elevated CRP = combined iron deficiency and inflammation 1
• Soluble transferrin receptor (sTfR) if available: high in iron deficiency, normal/low in anemia of chronic disease 1

Special Population Considerations

Chronic Kidney Disease Patients on ESAs

• Target ferritin >200 ng/mL and transferrin saturation >20% for optimal ESA response 1
• Iron therapy may benefit patients even with ferritin 500-1200 ng/mL if transferrin saturation remains <25% 1
• Monitor ferritin every 1-3 months depending on level; more frequently as it approaches normal range 1

Heart Failure Patients

• Transferrin saturation <20% with ferritin >300 ng/mL indicates functional iron deficiency from inflammation 1
• Consider reticulocyte hemoglobin content (CHr) <30 pg as predictor of IV iron response 1
• Iron deficiency prevalence is 50-70% in this population despite "normal" ferritin 1

Pre-menopausal Women

• Ferritin thresholds may need adjustment upward to 50 ng/mL as physiologic cutoff, since 30-50% of healthy women have no marrow iron stores 2
• Standard reference ranges underdiagnose iron deficiency in women 2
• For asymptomatic pre-menopausal women with iron deficiency anemia, empiric iron supplementation is reasonable before pursuing invasive testing 1

Management Based on Iron Studies

Iron Deficiency Confirmed (Ferritin <45 ng/mL without inflammation)

For men and post-menopausal women:

• Perform non-invasive testing for H. pylori and celiac disease 1
• Strong recommendation for bidirectional endoscopy if testing negative 1
• Initiate iron supplementation concurrently with treating underlying cause 1

For pre-menopausal women:

• Consider empiric iron supplementation trial first, especially in younger women 1
• Pursue endoscopy if symptoms present or iron supplementation fails 1

Iron Supplementation Strategy

• Oral iron is first-line for uncomplicated iron deficiency 1
• IV iron indicated when: oral iron fails, malabsorption present, inflammation limits oral absorption, or rapid repletion needed 1
• Target ferritin >100 ng/mL for iron store restoration 1
• In chronic kidney disease, avoid ferritin >500 ng/mL to prevent potential iron overload 1

Monitoring Response

• Recheck hemoglobin and ferritin after iron supplementation trial 1
• If anemia persists despite ferritin >100 ng/mL, investigate alternative causes 1
• Long-term monitoring every 6-12 months as recurrence exceeds 50% at one year 1

Key pitfall: Do not rely on serum iron and TIBC alone—ferritin detects iron deficiency in many cases where iron/TIBC appear normal, particularly when TIBC is abnormal 3. Always interpret the complete iron panel together with clinical context and inflammatory markers.