How are absolute iron deficiency (ID), functional iron deficiency (ID), and iron deficiency due to low storage classified?

Classification of Iron Deficiency Types

Iron deficiency can be classified into three main types: absolute iron deficiency, functional iron deficiency, and iron deficiency due to low storage, each with distinct diagnostic parameters and clinical implications. 1, 2

Absolute Iron Deficiency

Absolute iron deficiency represents a true depletion of iron stores in the body and is characterized by:

• Diagnostic criteria:

  • Serum ferritin <30 μg/L in patients without inflammation 2
  • Serum ferritin <100 ng/mL in predialysis and peritoneal dialysis patients 1, 3
  • Serum ferritin <200 ng/mL in hemodialysis patients 3
  • Transferrin saturation (TSAT) <20% 1, 2

• Causes:

  • Reduced iron intake (malnutrition, dietary restrictions)
  • Blood loss (menstruation, gastrointestinal bleeding)
  • Malabsorption (celiac disease, gastric surgery)
  • Increased iron requirements (pregnancy, growth) 1, 4

Functional Iron Deficiency

Functional iron deficiency occurs when there are adequate iron stores but impaired iron mobilization from storage sites to support erythropoiesis:

• Diagnostic criteria:

  • TSAT <20% (reflecting impaired iron availability)
  • Normal or elevated serum ferritin (100-700 ng/mL) 1
  • Often occurs during erythropoietin therapy or in inflammatory conditions

• Mechanisms:

  • Increased hepcidin production due to inflammation
  • Blocked iron absorption from gastrointestinal tract
  • Impaired iron mobilization from reticuloendothelial system 1, 3
  • Can be distinguished from inflammatory iron block by monitoring ferritin levels during treatment 1

Iron Deficiency Due to Low Storage

This classification refers to depleted iron reserves that haven't yet manifested as absolute deficiency:

• Diagnostic criteria:
  • Early-stage iron depletion
  • Reduced bone marrow iron stores
  • Normal or slightly reduced TSAT
  • Ferritin levels at the lower end of normal range 1

Diagnostic Considerations

When evaluating iron status, it's important to consider:

1. Inflammatory status: Inflammation can mask underlying iron deficiency by elevating ferritin levels

   • In inflammatory conditions, ferritin threshold for iron deficiency increases to <100 μg/L 2
   • C-reactive protein should be measured alongside ferritin to assess inflammation 2, 5

2. Additional laboratory parameters:

   • Reticulocyte hemoglobin content and percentage of hypochromic RBCs can provide functional assessment of iron availability 1
   • Mean corpuscular volume (MCV) - typically low in iron deficiency
   • Red cell distribution width (RDW) - typically elevated in iron deficiency 2

3. Clinical context:

   • Chronic kidney disease patients often have both absolute and functional iron deficiency 3
   • Heart failure patients have high prevalence of iron deficiency (37-61%) 4
   • Inflammatory bowel disease patients have high prevalence of iron deficiency (13-90%) 4

Clinical Implications

The classification of iron deficiency type has important implications for treatment:

• Absolute iron deficiency: Requires iron replacement therapy (oral or IV) to replenish stores
• Functional iron deficiency: May require IV iron to bypass hepcidin blockade, especially in inflammatory conditions
• Low storage iron deficiency: Early intervention with oral iron may prevent progression to more severe deficiency 2, 4

Monitoring Response to Treatment

• Hemoglobin should increase by 1-2 g/dL within 4-8 weeks of treatment
• Target parameters include ferritin ≥50 μg/L and TSAT >20% 2
• In functional iron deficiency, response to IV iron can help distinguish from inflammatory iron block 1

Understanding these classifications is crucial for appropriate diagnosis and management of iron deficiency, particularly in patients with chronic inflammatory conditions where traditional diagnostic parameters may be less reliable.