What is the evaluation and management approach for anemia of chronic disease?

Evaluation and Management of Anemia of Chronic Disease

The evaluation of anemia of chronic disease requires a comprehensive laboratory workup including complete blood count, reticulocyte count, iron studies, and assessment for underlying inflammatory conditions, followed by targeted management of the underlying disease and consideration of iron supplementation or erythropoiesis-stimulating agents when appropriate.

Diagnostic Criteria and Initial Evaluation

• Anemia of chronic disease (ACD) is defined as hemoglobin <135 g/L in adult males and <120 g/L in adult females in the context of chronic inflammatory, infectious, or neoplastic disorders 1, 2
• ACD is the second most common type of anemia after iron deficiency anemia worldwide 3, 4
• Initial laboratory evaluation should include:
  • Complete blood count with red cell indices (typically normocytic, normochromic but can be microcytic in 30-50% of cases) 1, 5
  • Reticulocyte count to assess bone marrow response (typically low in ACD) 1, 2
  • Iron studies including serum iron, ferritin, transferrin saturation, and total iron-binding capacity 1, 2

Distinguishing Features of Anemia of Chronic Disease

• Characteristic laboratory findings include:
  • Low serum iron 1, 3
  • Low or normal transferrin and total iron-binding capacity (TIBC) 6, 7
  • Low transferrin saturation (<20%) 6
  • Normal or elevated ferritin (>100 μg/L) 1, 6
  • Low reticulocyte count or index 1, 2
• These findings contrast with iron deficiency anemia, which typically shows low ferritin and elevated TIBC 7, 8

Additional Testing Based on Clinical Context

• Evaluate for underlying conditions commonly associated with ACD:
  • Chronic inflammatory disorders (rheumatoid arthritis, inflammatory bowel disease) 3, 4
  • Chronic infections 4
  • Malignancies 3, 4
  • Chronic kidney disease 1, 2
• Additional tests to consider:
  • Kidney function tests to evaluate for renal disease 2
  • Inflammatory markers (C-reactive protein, erythrocyte sedimentation rate) 3
  • Vitamin B12 and folate levels to rule out deficiencies 2
  • Hepcidin levels may be helpful (elevated in ACD) but are not widely available 3

Management Approach

• The primary management strategy for anemia of chronic disease is treatment of the underlying disorder, supplemented by targeted interventions for the anemia itself when clinically significant 3, 4

• Treatment of underlying condition:

  • Address the primary inflammatory, infectious, or neoplastic disorder 3, 4
  • Monitor hemoglobin response to treatment of the underlying condition 2

• Iron supplementation:

  • Consider iron supplementation if there is evidence of concomitant iron deficiency 6
  • In patients with normal iron stores but functional iron deficiency (TSAT <20% with ferritin >100 μg/L), iron supplementation may still be beneficial 6
  • Intravenous iron may be preferred over oral iron in the context of inflammation 3

• Erythropoiesis-stimulating agents (ESAs):

  • Consider ESAs in severe or symptomatic anemia, particularly in chronic kidney disease 9, 10
  • Important cautions with ESAs:
    • Target hemoglobin should not exceed 11 g/dL due to increased risks of death, cardiovascular events, and stroke 9, 10
    • Use the lowest dose sufficient to reduce the need for red blood cell transfusions 9
    • Monitor hemoglobin weekly after initiation or dose adjustment until stable 9, 10
    • ESAs are not indicated for use in cancer patients when the anticipated outcome is cure 9

• Blood transfusions:

  • Reserve for severe, symptomatic anemia or hemodynamic instability 2
  • Consider risks and benefits of transfusion versus other treatment options 2

Follow-up and Monitoring

• Monitor hemoglobin weekly after treatment initiation until stable, then monthly 9, 10
• Evaluate iron status regularly during treatment 9, 10
• For patients on ESAs:
  • Reduce dose by 25% or more if hemoglobin rises rapidly (>1 g/dL in 2 weeks) 9, 10
  • Increase dose by 25% if hemoglobin has not increased by >1 g/dL after 4 weeks 9, 10
  • Discontinue if no response after 12 weeks of escalating therapy 9, 10

Common Pitfalls and Considerations

• Mixed anemia (combined iron deficiency and ACD) can be challenging to diagnose as inflammatory states alter conventional iron parameters 8
• Ferritin is an acute phase reactant and may be elevated in inflammatory states despite iron deficiency 1, 6
• Standard definitions of anemia may not apply to certain populations (pregnant women, elderly, those living at high altitude, smokers) 1
• Avoid excessive iron supplementation in patients with adequate iron stores as this may worsen inflammation 3
• Consider hematology consultation for complex or refractory cases 1