What is the initial workup and treatment for anemia of chronic disease?

Initial Workup and Treatment for Anemia of Chronic Disease

The initial workup for anemia of chronic disease should include a complete blood count with indices, reticulocyte count, iron studies (serum iron, TIBC, ferritin, transferrin saturation), and vitamin B12 and folate levels to distinguish it from other causes of anemia and guide appropriate treatment. 1

Diagnostic Approach

Step 1: Laboratory Evaluation

• Complete blood count (CBC) with indices
• Reticulocyte count
• Iron studies:
  • Serum iron
  • Total iron-binding capacity (TIBC)
  • Serum ferritin
  • Transferrin saturation (TSAT)
• Vitamin B12 and folate levels
• Peripheral blood smear examination

Step 2: Differential Diagnosis

Anemia of chronic disease typically presents with:

• Normocytic, normochromic anemia (though can be microcytic in 30-50% of cases)
• Low serum iron
• Low/normal TIBC (unlike iron deficiency where TIBC is high)
• Normal or elevated ferritin (>100 μg/L)
• Low transferrin saturation (<20%)
• Low reticulocyte count
• Evidence of underlying inflammatory condition

Key laboratory differences between anemia of chronic disease and iron deficiency anemia:

Parameter	Iron Deficiency Anemia	Anemia of Chronic Disease
MCV	Low (microcytic)	Normal (typically)
Serum iron	Low	Low
TIBC	High	Low/Normal
Ferritin	< 30 μg/L	> 100 μg/L
Transferrin saturation	< 15%	< 20%

Step 3: Identify Underlying Condition

Search for the underlying chronic inflammatory, infectious, autoimmune, or neoplastic disorder that is causing the anemia. Common conditions include:

• Chronic kidney disease
• Inflammatory bowel disease
• Rheumatoid arthritis
• Cancer
• Chronic infections

Treatment Algorithm

First-Line Approach

1. Treat the underlying disease - This is the most important and effective strategy for resolving anemia of chronic disease 1, 2

2. Evaluate for concurrent iron deficiency

   • If concurrent iron deficiency is present (ferritin <100 μg/L and TSAT <20%), provide iron supplementation:
     • Oral iron: Ferrous sulfate 325 mg daily or on alternate days 1
     • If oral iron is ineffective or poorly tolerated, consider intravenous iron

3. Check for other nutritional deficiencies

   • If B12 deficiency is present: Hydroxocobalamin 1 mg IM three times weekly for 2 weeks, then 1 mg IM every 2-3 months 1
   • If folate deficiency is present: Oral folic acid 5 mg daily for at least 4 months 1
   • Important: Always rule out B12 deficiency before treating folate deficiency to avoid masking B12 deficiency 1

Second-Line Approach

If anemia persists despite treating the underlying condition and correcting nutritional deficiencies:

1. Consider Erythropoiesis-Stimulating Agents (ESAs)
   • ESAs should be considered when:
     • Hemoglobin remains <10 g/dL despite addressing underlying causes
     • Patient is symptomatic from anemia
     • The benefits outweigh the risks
   • Target hemoglobin: 10-11 g/dL (not higher due to increased cardiovascular risks) 1, 3
   • Monitor hemoglobin every 2-4 weeks initially, then monthly 1
   • Continue iron supplementation throughout ESA therapy to ensure adequate iron availability 1

Important Cautions

1. ESA Risks: ESAs increase the risk of death, myocardial infarction, stroke, venous thromboembolism, and tumor progression/recurrence. Use the lowest dose sufficient to reduce the need for red blood cell transfusions 3

2. Iron Monitoring: Continue to monitor iron indices regularly during treatment to ensure adequate iron availability for erythropoiesis 1

3. Ferritin Interpretation: Remember that ferritin is an acute phase reactant and may be elevated despite iron deficiency. Consider the entire clinical picture and all iron indices 1

4. Transfusion Consideration: For severe symptomatic anemia, red blood cell transfusion may be necessary while other treatments are being initiated

By following this systematic approach to diagnosis and treatment, anemia of chronic disease can be effectively managed while addressing the underlying condition that is driving the anemic process.