What are the markers and treatment options for iron deficiency?

Iron Deficiency Markers and Treatment

Serum ferritin is the single most useful marker for diagnosing iron deficiency, with levels <30 μg/L generally indicating low body iron stores in the absence of inflammation. 1

Diagnostic Markers for Iron Deficiency

Primary Markers

• Serum ferritin:

  • <15 μg/L: Highly specific for iron deficiency (specificity 0.99) 1
  • <30 μg/L: Indicates low body iron stores 1
  • In inflammatory conditions: Values up to 100 μg/L may still be consistent with iron deficiency 1

• Transferrin saturation:

  • <20%: Suggests iron deficiency 1
  • More reliable than ferritin in inflammatory states as it's less affected by inflammation 1

Secondary Markers

• Complete blood count parameters:

  • Mean Corpuscular Volume (MCV): Low in iron deficiency (microcytosis) 2
  • Mean Corpuscular Hemoglobin (MCH): More reliable marker than MCV as it's less dependent on storage and counting machines 1
  • Red Cell Distribution Width (RDW): Elevated in iron deficiency 1

• Other biochemical tests:

  • Serum iron: Low in iron deficiency 1
  • Total Iron-Binding Capacity (TIBC): Elevated in iron deficiency 1
  • Reticulocyte hemoglobin content (CHr): Higher sensitivity and specificity than ferritin and transferrin saturation 1
  • Percentage of hypochromic red blood cells (PHRBC): Useful but time-sensitive 1
  • Soluble transferrin receptor: Increased in iron deficiency and not affected by inflammation 2

Diagnostic Algorithm for Iron Deficiency

1. Initial assessment:

   • Complete blood count with indices
   • Serum ferritin
   • Transferrin saturation

2. Interpretation:

   • Absolute iron deficiency: Ferritin <30 μg/L, transferrin saturation <20% 1, 2
   • Functional iron deficiency with inflammation: Ferritin 30-100 μg/L, transferrin saturation <20% 1
   • Anemia of chronic disease: Ferritin >100 μg/L, transferrin saturation <20% 1, 2

3. Confirmatory approach:

   • Therapeutic trial: A good response to iron therapy (Hb rise ≥10 g/L within 2 weeks) is highly suggestive of iron deficiency, even with equivocal iron studies 1

Treatment Options for Iron Deficiency

Oral Iron Therapy

• First-line treatment for most patients 2, 3
• Dosing: Ferrous sulfate 325 mg daily or on alternate days 3
• Duration: Continue for 3-6 months after normalization of hemoglobin to replenish stores

Intravenous Iron Therapy

• Indications:
  • Oral iron intolerance
  • Poor absorption (celiac disease, post-bariatric surgery)
  • Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
  • Ongoing blood loss
  • Second and third trimesters of pregnancy 3

Special Considerations

Iron Deficiency with Inflammation

• In inflammatory states, ferritin acts as an acute phase reactant and may be falsely elevated 1
• Use transferrin saturation or soluble transferrin receptor for more accurate assessment 1, 2
• Consider a ferritin cutoff of up to 100 μg/L in patients with inflammatory conditions 1

Common Pitfalls to Avoid

• Relying solely on hemoglobin and hematocrit, which are late indicators of iron deficiency 1
• Misinterpreting normal ferritin in inflammatory states 2
• Overlooking gastrointestinal causes of iron deficiency, especially in males >50 years 2
• Failing to investigate the cause of iron deficiency, particularly in non-menstruating individuals 1

Monitoring Response to Treatment

• Check hemoglobin after 2-4 weeks of treatment initiation 2
• Monitor iron studies every 3 months during the first year 2
• Annual monitoring after the first year unless risk factors are present 2

By following this systematic approach to diagnosing and treating iron deficiency, clinicians can effectively manage this common condition and improve patient outcomes related to morbidity, mortality, and quality of life.