What does low serum ferritin and low Total Iron Binding Capacity (TIBC) with normal iron level indicate?

Low Serum Ferritin and Low TIBC with Normal Iron: Diagnostic Interpretation

Low serum ferritin with low TIBC and normal iron levels most likely indicates anemia of chronic disease (ACD) with concurrent true iron deficiency in the setting of inflammation.

Interpretation of Iron Studies

Key Laboratory Findings

• Low serum ferritin: Typically indicates depleted iron stores
• Low TIBC (Total Iron Binding Capacity): Suggests inflammation or chronic disease
• Normal serum iron: Can occur in mixed iron deficiency and inflammatory states

Diagnostic Framework

1. In non-inflammatory states:

   • Ferritin <30 μg/L definitively indicates iron deficiency 1
   • Low TIBC is unusual in isolated iron deficiency (TIBC typically increases)

2. In inflammatory states:

   • Ferritin up to 100 μg/L may still indicate iron deficiency 1
   • Low TIBC is common due to transferrin being a negative acute-phase reactant
   • This pattern suggests a combination of true iron deficiency and anemia of chronic disease 1

Clinical Significance

Underlying Mechanisms

• Inflammation triggers hepcidin production, which:

  • Restricts dietary iron uptake
  • Promotes iron sequestration in storage sites
  • Results in functional iron deficiency despite normal serum iron 2

• Ferritin increases during inflammation (acute-phase reactant)

  • Makes interpretation challenging
  • Low ferritin despite inflammation strongly suggests severe iron deficiency

Common Causes

1. Inflammatory bowel disease (IBD)

   • Particularly active ulcerative colitis or Crohn's disease 1
   • Combination of blood loss and inflammation

2. Other chronic inflammatory conditions

   • Chronic kidney disease
   • Chronic heart failure
   • Autoimmune disorders

3. Obesity-related inflammation

   • Ferritin can be elevated due to inflammation rather than adequate iron stores 3
   • TIBC may be low despite true iron deficiency

Recommended Approach

Additional Testing

• Check inflammatory markers (CRP, ESR) to confirm inflammatory state 1, 4
• Consider transferrin saturation (TSAT) - values <20% suggest iron deficiency even with normal iron 4, 2
• Evaluate reticulocyte hemoglobin content (CHr) - values <30 pg suggest iron-restricted erythropoiesis 4
• Complete blood count to assess for anemia and red cell indices

Diagnostic Thresholds in Inflammation

• Ferritin 30-100 μg/L with TSAT <20% suggests combined iron deficiency and ACD 1, 4
• Ferritin >100 μg/L with TSAT <20% suggests pure ACD 1

Investigation for Underlying Cause

• Gastrointestinal evaluation is particularly important in men and postmenopausal women 4
• Screen for IBD if GI symptoms are present
• Consider other sources of chronic inflammation

Treatment Considerations

• Treat underlying inflammatory condition first 1
• Iron supplementation may be needed:
  • Oral iron: First-line in mild deficiency without severe inflammation
  • IV iron: Consider if oral iron ineffective or in severe inflammation 4
• Monitor response with ferritin, TSAT, and hemoglobin levels

Common Pitfalls

• Relying solely on ferritin without considering inflammatory status 2
• Using standard ferritin cutoffs (30 μg/L) in inflammatory states 1
• Overlooking the need to investigate underlying causes of iron deficiency
• Failing to recognize that transferrin/TIBC measurement often outperforms iron measurement in predicting iron deficiency 5