What is the treatment approach for anemia due to chronic disease?

Treatment Approach for Anemia of Chronic Disease

The treatment of anemia of chronic disease should prioritize optimizing the management of the underlying inflammatory condition, combined with iron supplementation and erythropoiesis-stimulating agents (ESAs) when appropriate. 1, 2

Understanding Anemia of Chronic Disease

Anemia of chronic disease (ACD), also known as anemia of inflammation, is the second most common type of anemia worldwide after iron deficiency anemia 3. It occurs in patients with:

• Chronic inflammatory conditions (IBD, rheumatoid arthritis)
• Infections
• Malignancies
• Chronic kidney disease
• Congestive heart failure
• Chronic pulmonary diseases
• Obesity

The pathophysiology involves:

• Inflammation-induced cytokines and hepcidin blocking intestinal iron absorption
• Iron retention in reticuloendothelial cells
• Shortened erythrocyte half-life
• Suppressed erythropoietin response
• Inhibition of erythroid cell differentiation 3

Diagnostic Evaluation

Before initiating treatment, confirm the diagnosis:

• Complete blood count (CBC) with hemoglobin, hematocrit, MCV, and RDW
• Iron studies:
  • Serum ferritin (typically normal or elevated in ACD)
  • Transferrin saturation (typically low in ACD)
  • Total iron binding capacity (TIBC) (typically low in ACD)
• Reticulocyte count (typically low in ACD)
• Inflammatory markers (ESR, CRP)
• Renal function tests (BUN, creatinine, GFR)
• Consider vitamin B12 and folate levels 1, 2

Treatment Algorithm

Step 1: Treat the Underlying Disease

• Optimize treatment of the primary inflammatory condition 1
  • For IBD: achieve complete remission of intestinal inflammation
  • For other inflammatory conditions: use appropriate disease-modifying therapies

Step 2: Correct Nutritional Deficiencies

• Evaluate and correct iron deficiency:
  • If serum ferritin <30 μg/L or transferrin saturation <20%, provide iron supplementation 1
  • For patients with active inflammation, ferritin up to 100 μg/L may still indicate iron deficiency 2
• Check and correct vitamin B12 and folate deficiencies if present 1, 2

Step 3: Iron Supplementation

Oral Iron:

• First-line for mild anemia without active inflammation
• Typical dose: ferrous sulfate 200 mg three times daily 2
• Continue for 2-3 months after hemoglobin normalization to replenish stores

Intravenous Iron:

• Indicated for:
  • Intolerance to oral iron
  • Poor absorption
  • Severe anemia (Hb <10 g/dL)
  • Active inflammatory disease (especially IBD)
  • Insufficient response to oral iron 1, 2

Step 4: Consider Erythropoiesis-Stimulating Agents (ESAs)

• Consider ESA therapy for patients with:
  • Insufficient response to iron supplementation
  • Optimized treatment of underlying disease
  • Ruled out or corrected nutritional deficiencies 1
• Target hemoglobin level should not exceed 12 g/dL 1, 4
• Important safety considerations:
  • ESAs increase risk of death, myocardial infarction, stroke, and thromboembolism when targeting Hb >11 g/dL 4
  • Use the lowest effective dose to reduce need for transfusions
  • Monitor for hypertension and thrombotic events

Step 5: Red Blood Cell Transfusion

• Reserve for patients with:
  • Hemoglobin <7 g/dL
  • Symptomatic anemia with hemodynamic instability
  • Failure of other treatments 1, 2
• Follow transfusions with IV iron supplementation 1

Special Considerations

Chronic Kidney Disease

• ESAs are indicated for anemia due to CKD
• Initial dose: 50-100 Units/kg three times weekly
• Monitor hemoglobin weekly after initiation and dose adjustments
• Target hemoglobin should not exceed 11 g/dL 1, 4

Cancer-Related Anemia

• ESAs are indicated only for chemotherapy-induced anemia
• Not for use in cancer patients receiving hormonal agents or radiotherapy alone
• Not for use when anticipated outcome is cure
• Discontinue following completion of chemotherapy 4

Common Pitfalls to Avoid

1. Misdiagnosing iron deficiency anemia as ACD: Ferritin can be elevated in inflammation despite iron deficiency
2. Overlooking mixed anemias: Multiple causes of anemia may coexist, especially in elderly patients
3. Targeting excessive hemoglobin levels: Aiming for Hb >11 g/dL with ESAs increases cardiovascular risks
4. Failing to treat the underlying condition: Optimal management of the primary disease is essential
5. Premature discontinuation of iron therapy: Continue until iron stores are replenished
6. Neglecting to monitor for ESA complications: Regular assessment for hypertension and thrombotic events is crucial

By following this structured approach, clinicians can effectively manage anemia of chronic disease while minimizing risks and optimizing patient outcomes.