What labs are recommended for diagnosing anemia of chronic disease?

Laboratory Evaluation for Anemia of Chronic Disease

For diagnosing anemia of chronic disease, obtain a complete blood count with differential, reticulocyte count, complete iron panel (serum iron, TIBC, ferritin, transferrin saturation), and inflammatory markers (CRP or ESR) to distinguish it from iron deficiency and identify coexisting deficiencies. 1, 2

Initial Laboratory Panel

The essential first-line tests include:

• Complete Blood Count (CBC) with differential and red cell indices to characterize the anemia morphologically—anemia of chronic disease typically presents as normocytic and normochromic 3, 1, 2

• Reticulocyte count (corrected for degree of anemia) to assess bone marrow response—a low or inappropriately normal count indicates impaired erythropoiesis characteristic of anemia of chronic disease 3, 1, 2

• Complete iron panel including serum iron, total iron-binding capacity (TIBC), serum ferritin, and transferrin saturation to differentiate from iron deficiency 1, 2

• Inflammatory markers such as C-reactive protein (CRP) or ESR to confirm chronic inflammation and aid in interpreting ferritin levels, since ferritin is an acute phase reactant 3, 1

Characteristic Laboratory Pattern

Anemia of chronic disease demonstrates a distinct pattern that distinguishes it from iron deficiency:

• Low serum iron with low-normal or low TIBC (unlike iron deficiency which has elevated TIBC) 1, 4

• Normal-to-elevated ferritin (typically >100 μg/L), reflecting adequate or increased iron stores despite low circulating iron 1, 5, 4

• Transferrin saturation >20% in pure anemia of chronic disease 3, 1

• Mild to moderate anemia with hemoglobin typically not severely depressed 5, 4

Distinguishing from Iron Deficiency

This is the most critical diagnostic challenge, as the two conditions frequently coexist:

• Pure iron deficiency: ferritin <30 μg/L without inflammation, or <100 μg/L with inflammation, plus transferrin saturation <16-20% 3, 6, 2

• Pure anemia of chronic disease: ferritin >100 μg/L, transferrin saturation >20%, elevated inflammatory markers 3, 1

• Combined picture (functional iron deficiency): ferritin 30-100 μg/L with transferrin saturation <20%—this indicates both true iron deficiency and anemia of chronic disease coexist 3, 1

Critical pitfall: In the presence of inflammation, ferritin can be falsely elevated up to 100 μg/L despite true iron deficiency, so never rely on ferritin alone when inflammatory markers are elevated 3, 6, 2

Additional Screening Tests

Based on clinical context, obtain:

• Vitamin B12 and folate levels if macrocytosis is present (MCV >100 fL) or if combined deficiencies are suspected 6, 1, 2

• Thyroid function tests to exclude hypothyroidism as a contributor 1

• Renal function tests (creatinine, BUN) since chronic kidney disease commonly causes anemia of chronic disease 3, 1

• Stool guaiac test if any suggestion of gastrointestinal bleeding exists 1, 2

Advanced Testing (When Available)

For complex cases or when standard tests are equivocal:

• Percent hypochromic red blood cells (PHRBC) and reticulocyte hemoglobin content (CHr) have sensitivities and specificities equal to or greater than ferritin and transferrin saturation for identifying functional iron deficiency, though they require specialized equipment 3, 2

• Soluble transferrin receptor can help distinguish anemia of chronic disease from iron deficiency, as it remains normal in pure anemia of chronic disease but is elevated in iron deficiency 7

• Bone marrow examination should be considered only if abnormalities in multiple cell lines are present, suggesting a primary bone marrow disorder 3, 2

Interpretation Algorithm

Follow this sequence:

1. Confirm anemia: Hemoglobin <13 g/dL in men, <12 g/dL in non-pregnant women 6

2. Check MCV: Anemia of chronic disease is typically normocytic (80-100 fL), though can be mildly microcytic 3, 5

3. Assess reticulocyte count: Low or inappropriately normal indicates hypoproliferative anemia 3, 1

4. Evaluate iron studies with inflammatory markers together:

   • If ferritin >100 μg/L + transferrin saturation >20% + elevated CRP/ESR = pure anemia of chronic disease 3, 1
   • If ferritin <30 μg/L (or <100 μg/L with inflammation) + transferrin saturation <20% = iron deficiency 3, 6
   • If ferritin 30-100 μg/L + transferrin saturation <20% = combined picture 3, 1

5. Screen for other deficiencies: Check B12/folate if indicated by MCV or clinical suspicion 6, 1