What is the management approach for a patient with anemia of chronic disease, particularly those with underlying conditions such as chronic kidney disease, rheumatoid arthritis, or cancer?

Management of Anemia of Chronic Disease

Treat the underlying inflammatory condition first before initiating anemia-specific therapy, as controlling inflammation often improves hemoglobin levels, then use intravenous iron as first-line anemia treatment, reserving erythropoiesis-stimulating agents only for patients with inadequate response to IV iron and optimized disease management. 1

Initial Diagnostic Workup

Iron Studies and CBC:

• Measure ferritin and transferrin saturation together, as ferritin alone is unreliable in inflammatory states due to acute phase reactant elevation 1
• Check complete blood count with red cell indices; anemia of chronic disease typically presents as normocytic and normochromic 1
• Use transferrin saturation <20% to support iron deficiency diagnosis when ferritin is equivocal 2

Assess Renal Function:

• Measure GFR and creatinine in all patients, as CKD is a major contributor when GFR <60 mL/min/1.73m² 1
• Anemia prevalence increases dramatically with declining kidney function: 5-7.5% at CKD stage 3,22-27% at stage 4, and 33-52% at stage 5 3
• Screen hemoglobin at least annually in all CKD patients, with more frequent monitoring in diabetic patients who develop anemia earlier and more severely 3

Exclude Other Causes:

• Perform stool guaiac testing to rule out occult blood loss, especially in elderly patients or those on antiplatelet/anticoagulant therapy 1
• Screen for vitamin B12 and folate deficiency only if macrocytosis is present or high clinical suspicion exists, as deficiency rates are low (<4%) in most chronic disease populations 1

Treatment Algorithm

Step 1: Optimize Primary Disease Management

• Aggressively treat the underlying condition (rheumatoid arthritis, inflammatory bowel disease, cancer) before starting anemia-specific therapy 1
• In rheumatoid arthritis patients, optimize anti-inflammatory therapy first, as this directly improves hemoglobin 1

Step 2: Intravenous Iron Therapy

• Use IV iron as first-line treatment in most chronic disease states, as it bypasses intestinal absorption blocked by hepcidin and directly replenishes iron stores 1
• Avoid oral iron in dialysis patients or severe inflammatory states, as it is ineffective due to hepcidin blockade 1
• IV iron is preferred over oral formulations because inflammation-induced hepcidin blocks intestinal iron absorption and iron release from macrophages 4, 5

Step 3: Erythropoiesis-Stimulating Agents (ESAs)

• Consider ESAs only after optimizing disease treatment and ensuring adequate iron stores 1
• FDA-approved indications for epoetin alfa include: anemia due to CKD (dialysis and non-dialysis patients), anemia from myelosuppressive chemotherapy in cancer patients with ≥2 months of planned chemotherapy remaining, and anemia due to zidovudine in HIV patients 6, 7
• Target hemoglobin ≤12 g/dL with ESAs; avoid targeting >12 g/dL as this increases cardiovascular risks without improving quality of life 1
• ESAs have not been shown to improve quality of life, fatigue, or patient well-being 6, 7

Disease-Specific Considerations

Chronic Kidney Disease

• The primary cause is insufficient erythropoietin production by diseased kidneys, with anemia developing when GFR falls below 20-35 mL/min/1.73 m² 3
• Additional contributing factors include iron deficiency from blood loss, inflammation with elevated hepcidin, hyperparathyroidism, and shortened red blood cell survival 3
• Use the lowest ESA dose sufficient to reduce transfusion needs rather than normalize hemoglobin 3
• Newer hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) offer oral administration and may improve iron utilization in inflammatory states, though long-term safety data remain limited 3, 4

Rheumatoid Arthritis and Inflammatory Conditions

• Prioritize optimizing anti-inflammatory therapy, as controlling inflammation directly improves hemoglobin levels 1
• Inflammatory cytokines inhibit erythropoietin production and directly impair erythroblast growth 3

Cancer Patients

• Distinguish between anemia from malignancy itself versus chemotherapy-induced anemia 1
• ESAs are indicated only for patients with non-myeloid malignancies receiving myelosuppressive chemotherapy with ≥2 months of planned treatment remaining 6, 7
• ESAs are contraindicated in patients receiving hormonal agents, biologics, or radiotherapy alone, when the anticipated outcome is cure, or when anemia can be managed by transfusion 6, 7
• Screen for nutritional deficiencies, though prevalence is low 1

Critical Pitfalls to Avoid

Diagnostic Errors:

• Never rely solely on ferritin in inflammatory conditions; always use transferrin saturation as well 1
• Do not assume mild anemia is less significant than severe anemia as an indicator of serious disease 2
• Investigate the entire gastrointestinal tract in elderly patients with iron deficiency anemia to rule out malignancy, even with a history of nutritional deficiency 2

Treatment Errors:

• Avoid oral iron as first-line in dialysis patients or severe inflammatory states due to hepcidin blockade 1
• Never target hemoglobin >12 g/dL with ESAs due to increased cardiovascular risks 1
• Do not use ESAs as a substitute for immediate RBC transfusions when rapid correction is needed 6, 7
• Avoid iron monotherapy in active infections or malignancy, as iron promotes microbial and tumor cell growth and inhibits T-cell-mediated immunity 8