Treatment Approach for Anemia of Chronic Disease
The primary approach to managing anemia of chronic disease (ACD) should focus on treating the underlying inflammatory condition, with intravenous iron therapy considered for patients with iron deficiency, and erythropoiesis-stimulating agents (ESAs) reserved for those with insufficient response to these initial interventions. 1, 2
Understanding Anemia of Chronic Disease
- ACD is the second most common type of anemia after iron deficiency anemia, occurring in patients with chronic inflammatory conditions, autoimmune diseases, cancer, and kidney failure 3, 4
- The pathophysiology involves three key mechanisms: shortened erythrocyte survival, impaired proliferation of erythroid progenitor cells, and abnormalities in iron metabolism 5
- Hepcidin, a liver peptide upregulated by inflammatory cytokines, plays a central role by inhibiting iron absorption and macrophage iron release, leading to functional iron deficiency despite adequate iron stores 5, 4
- ACD typically presents as a normocytic, normochromic anemia with low serum iron, low transferrin, and normal or elevated ferritin levels 4
Diagnostic Approach
- Initial workup should include complete blood count, reticulocyte count, iron studies (serum iron, transferrin saturation, ferritin), and assessment of the underlying inflammatory condition 3
- Ferritin levels up to 100 μg/L in the presence of inflammation may still reflect iron deficiency; therefore, measurement of transferrin saturation is recommended 2
- Evaluate for other potential causes of anemia, including vitamin B12 and folate deficiency, especially in patients with macrocytosis 2
- In doubtful cases, measurement of homocysteine or methyl malonate can help diagnose vitamin deficiencies with greater sensitivity than serum B12 measurement 2
Treatment Algorithm
Step 1: Treat the Underlying Disease
- Optimizing treatment of the underlying inflammatory condition is the cornerstone of ACD management 1, 2
- Controlling inflammation can significantly improve hemoglobin levels, as demonstrated in studies with anti-TNF therapy in rheumatoid arthritis 2
Step 2: Address Iron Deficiency
- For patients with evidence of iron deficiency (transferrin saturation ≤20% and ferritin ≤500 ng/mL):
- Intravenous iron is preferred over oral iron in active inflammatory conditions, as inflammation inhibits oral iron absorption 2, 6
- Oral iron (no more than 100 mg elemental iron daily) may be considered only in patients with inactive disease 2
- If oral iron is not tolerated, consider reduced dosing (one tablet every other day) or switch to parenteral iron 2
Step 3: Consider Erythropoiesis-Stimulating Agents
- ESAs should be considered only for patients with:
- ESAs are contraindicated in patients with active malignancy due to potential for tumor progression 1
Step 4: Blood Transfusion (Last Resort)
- Reserve blood transfusions for:
- Blood transfusions should be followed by intravenous iron supplementation 2
Monitoring and Follow-up
- Measure hemoglobin at least every 3 months in patients with chronic disease and anemia 1
- Monitor iron parameters (ferritin, transferrin saturation) every 3 months during therapy 1
- Assess symptoms of anemia (fatigue, exercise tolerance, quality of life) at each visit 1
- Adjust therapy based on hemoglobin response, iron parameters, and symptom improvement 1
Special Considerations
- In patients with heart disease, use a restrictive red blood cell transfusion strategy (trigger hemoglobin threshold of 7-8 g/dL) 2
- For patients with heart failure or coronary heart disease, avoid ESAs for mild to moderate anemia due to potential cardiovascular risks 2
- In chronic kidney disease, follow specific guidelines for anemia management based on GFR 2
- For patients with inflammatory bowel disease, vitamin B12 and folate levels should be measured at least annually, or if macrocytosis is present 2