Management of Anemia of Chronic Disease
The primary treatment for anemia of chronic disease (ACD) should focus on addressing the underlying inflammatory condition while using targeted therapies including iron supplementation, erythropoiesis-stimulating agents (ESAs), and in severe cases, blood transfusions. 1
Diagnosis and Evaluation
Before initiating treatment, confirm ACD diagnosis through:
- Complete blood count
- Iron studies (typically shows low serum iron, decreased transferrin saturation, and normal or elevated ferritin)
- Inflammatory markers (elevated)
- Exclusion of other causes of anemia (B12/folate deficiency, blood loss)
Iron deficiency in chronic kidney disease (CKD) is defined as transferrin saturation ≤20% with ferritin ≤100 μg/L in predialysis patients or ≤200 μg/L in hemodialysis patients 2.
Treatment Algorithm
Step 1: Treat the Underlying Condition
- First priority: Optimize treatment of the primary inflammatory condition 1, 2
- For inflammatory bowel disease: Achieve mucosal healing with appropriate disease-modifying therapy 2
- For rheumatologic conditions: Control inflammation with immunosuppressive therapy
- For chronic kidney disease: Optimize renal management 2
Step 2: Iron Supplementation
- For functional iron deficiency, intravenous (IV) iron is preferred over oral iron in inflammatory conditions 1
- Oral iron is often ineffective due to hepcidin-mediated blockade of intestinal absorption 3
- Administer supplemental iron when serum ferritin is <100 μg/L or transferrin saturation is <20% 4
Step 3: Consider Erythropoiesis-Stimulating Agents (ESAs)
- Consider ESAs when hemoglobin remains <10 g/dL despite optimized disease treatment and iron therapy 1
- Important safety warning: ESAs increase the risk of death, myocardial infarction, stroke, and venous thromboembolism when targeting hemoglobin >11 g/dL 4
- Use the lowest dose sufficient to reduce the need for red blood cell transfusions 4
- Monitor hemoglobin weekly after initiation until stable, then monthly 4
Step 4: Blood Transfusions
- Reserve for severe anemia (Hb <7 g/dL) or symptomatic patients 1
- Use restrictive transfusion strategy (trigger Hb 7-8 g/dL) 1
- Follow transfusions with IV iron supplementation to replenish stores 1
Special Considerations by Disease Type
Chronic Kidney Disease
- ACD in CKD often requires both iron and ESAs 2
- When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable 4
- Do not increase ESA dose more frequently than once every 4 weeks 4
- Avoid targeting hemoglobin levels >11 g/dL due to increased cardiovascular risks 4
Inflammatory Bowel Disease
- Management should exclude other possible concomitant diseases such as infections, malignancies, and medication side effects 2
- Thiopurines can cause macrocytosis and mild anemia; consider dose adjustment if other causes are excluded 2
Cancer-Associated ACD
- ESAs are indicated only for anemia due to myelosuppressive chemotherapy 4
- ESAs are not indicated when the anticipated outcome of chemotherapy is cure 4
- Discontinue ESAs following completion of chemotherapy course 4
Emerging Therapies
New treatment strategies targeting the hepcidin-ferroportin axis are being developed 5, 3:
- Hepcidin antagonists
- Ferroportin stabilizers
- Agents that inhibit hepcidin production
Common Pitfalls to Avoid
- Treating with iron alone without addressing the underlying disease 1
- Using oral iron in conditions with significant inflammation 1, 3
- Targeting hemoglobin levels >12 g/dL with ESAs, which increases cardiovascular risks 1, 4
- Neglecting to monitor iron status during ESA therapy 1
- Overlooking vitamin B12 and folate deficiencies that may coexist with ACD 1
- Failing to recognize that shortened erythrocyte survival and impaired erythropoietin response also contribute to ACD 3
By addressing the underlying inflammatory condition while providing appropriate supportive care with iron, ESAs (when indicated), and transfusions (when necessary), most patients with ACD can achieve improvement in their anemia and associated symptoms.