How should anemia be evaluated and managed when serum ferritin is ≥30 µg/L?

Evaluation and Management of Anemia When Serum Ferritin is ≥30 µg/L

When serum ferritin is ≥30 µg/L, you must assess for inflammation and calculate transferrin saturation (TSAT) to distinguish between anemia of chronic disease, functional iron deficiency, and combined deficiency states—ferritin alone is insufficient for diagnosis in this range. 1

Diagnostic Algorithm Based on Ferritin Level and Inflammatory Status

Step 1: Assess for Inflammation

• Measure CRP and ESR immediately to determine if ferritin elevation reflects true iron stores or acute-phase reactant response 1
• Check complete blood count with MCV, reticulocyte count, and calculate transferrin saturation using the formula: (serum iron × 100) ÷ TIBC 1

Step 2: Interpret Ferritin in Context of Inflammation

If ferritin is 30-100 µg/L WITH elevated CRP/ESR:

• This represents a mixed picture of true iron deficiency combined with anemia of chronic disease 1
• Iron deficiency remains likely because inflammation falsely elevates ferritin, masking depleted stores 1, 2
• A TSAT <20% confirms iron deficiency requiring treatment, even with ferritin up to 100 µg/L 1, 2

If ferritin is 30-100 µg/L WITHOUT inflammation (normal CRP/ESR):

• This suggests borderline iron stores that may still warrant treatment, particularly if TSAT <20% 3, 4
• A ferritin threshold of <45 µg/L provides optimal sensitivity-specificity balance (92% specificity) for iron deficiency 5, 3

If ferritin is >100 µg/L WITH elevated CRP/ESR:

• Anemia of chronic disease (inflammatory iron block) is the primary diagnosis 1
• Diagnostic criteria: ferritin >100 µg/L AND TSAT <20% in presence of inflammation 1
• However, functional iron deficiency can still exist—check TSAT 1, 2
• If TSAT <20%, iron is sequestered and unavailable for erythropoiesis despite adequate stores 1, 2

If ferritin is >100 µg/L WITHOUT inflammation:

• Iron deficiency is unlikely; ferritin >150 µg/L rarely occurs with absolute iron deficiency 5, 3
• Investigate alternative causes of anemia (vitamin B12, folate deficiency, hemolysis, bone marrow disease) 1

Step 3: Additional Workup When Results Are Discordant

When ferritin and TSAT provide conflicting information:

• Measure soluble transferrin receptor (sTfR) 1, 6
• Elevated sTfR confirms true iron deficiency even in the presence of inflammation, as it is unaffected by acute-phase response 1, 4, 6
• The sTfR/log ferritin ratio (sTfR-F Index) ≥2 indicates iron deficiency; <1 indicates iron repletion 6

Assess reticulocyte count to guide further evaluation:

• Low or normal reticulocytes indicate deficiency states or bone marrow failure requiring investigation 1
• Elevated reticulocytes exclude deficiency and suggest hemolysis—measure haptoglobin, LDH, and bilirubin 1

Check MCV and RDW for additional clues:

• High RDW indicates iron deficiency even when MCV is normal (due to coexisting microcytosis and macrocytosis) 1
• Macrocytosis suggests vitamin B12 or folate deficiency, medication effect (azathioprine), or reticulocytosis 1

Treatment Decisions Based on Final Diagnosis

For confirmed iron deficiency (ferritin 30-100 µg/L with TSAT <20%):

• Initiate oral iron supplementation immediately with ferrous sulfate 65 mg elemental iron daily or alternate-day dosing 5, 7
• Treat underlying inflammation simultaneously, as this is essential for iron mobilization 1, 2
• Repeat CBC and ferritin at 8-10 weeks to assess response 5, 7

For anemia of chronic disease (ferritin >100 µg/L, TSAT <20%, elevated CRP/ESR):

• Treating the underlying inflammatory condition is the primary intervention 1
• Iron supplementation may still be beneficial if TSAT remains <20% despite treating inflammation 2

For functional iron deficiency (ferritin >100 µg/L, TSAT <20%, normal CRP/ESR):

• This indicates iron sequestration without inflammation—consider intravenous iron if oral supplementation fails 2, 7

Critical Pitfalls to Avoid

• Never assume ferritin ≥30 µg/L excludes iron deficiency—inflammation can elevate ferritin while true deficiency persists 1, 2, 4
• Never rely on ferritin alone—always calculate TSAT and assess inflammatory markers 1, 2
• Using the traditional ferritin cutoff of <15 µg/L misses the majority of iron deficiency cases due to poor sensitivity 3, 4
• A ferritin level >50 µg/L can still be consistent with iron deficiency, particularly in inflammatory conditions 2, 6
• In inflammatory bowel disease, chronic kidney disease, and chronic heart failure, use a ferritin threshold of <100 µg/L rather than <30 µg/L 1, 2

Special Population Considerations

In inflammatory bowel disease patients:

• Ferritin <30 µg/L indicates iron deficiency in remission 1
• Ferritin up to 100 µg/L may still indicate iron deficiency during active inflammation 1
• Monitor every 3 months in active disease, every 6-12 months in remission 3

In chronic kidney disease patients:

• Absolute iron deficiency is defined as ferritin <100 ng/mL AND TSAT <20% 5, 3, 2
• Functional iron deficiency occurs when ferritin is 100-700 ng/mL but TSAT <20% 5, 2