Blood Tests for Diagnosing Anemia of Chronic Disease
The diagnosis of anemia of chronic disease (ACD) requires a specific panel of blood tests including complete blood count (CBC), serum iron, total iron-binding capacity (TIBC), transferrin saturation, and serum ferritin, with the characteristic pattern showing low serum iron, low/normal TIBC, and elevated ferritin (>100 μg/L). 1
Key Diagnostic Tests
Primary Tests
- Complete Blood Count (CBC) - Shows hemoglobin levels typically in the mild to moderate anemia range 1, 2
- Serum Iron - Reduced in ACD 1, 3
- Total Iron-Binding Capacity (TIBC) - Low to normal in ACD (contrasts with iron deficiency anemia where TIBC is elevated) 1
- Transferrin Saturation - Typically <20% 1
- Serum Ferritin - Elevated (>100 μg/L) in ACD 1, 2
Additional Tests
- Reticulocyte Count - Decreased percentage, indicating reduced red blood cell production 1, 2
- Hepcidin Levels - Often elevated in ACD 1, 2
- Inflammatory Markers - C-reactive protein (CRP) to assess inflammation 4
- Vitamin B12 and Folate Levels - To exclude other causes of anemia 1
Differential Diagnostic Patterns
The key to diagnosing ACD is distinguishing it from iron deficiency anemia (IDA), which can be challenging as they may coexist. The following pattern is characteristic of ACD:
| Parameter | Anemia of Chronic Disease | Iron Deficiency Anemia |
|---|---|---|
| MCV | Normal (normocytic) | Low (microcytic) |
| Serum iron | Low | Low |
| TIBC | Low/Normal | High |
| Ferritin | >100 μg/L | <30 μg/L |
| Transferrin saturation | <20% | <15% |
| Reticulocyte count | Low | Low |
Advanced Diagnostic Approaches
When standard tests provide equivocal results, particularly in cases where ACD and IDA coexist:
- Soluble Transferrin Receptor (sTfR) - Elevated in iron deficiency but unaffected by inflammation 5
- sTfR/log Ferritin Index (sTfR Index) - Superior to sTfR alone for detecting combined ACD and IDA 5
Using all three parameters (ferritin, sTfR, and sTfR Index) can more than double the detection of iron deficiency in patients with chronic inflammation, from 41% (using ferritin alone) to 92% 5.
Clinical Context
ACD typically accompanies specific underlying conditions:
- Chronic inflammatory disorders
- Autoimmune diseases
- Cancer
- Chronic kidney disease
- Chronic infections
The severity of ACD generally correlates with the severity of the underlying disease 2. In patients with chronic kidney disease, the diagnostic criteria may differ slightly, with absolute iron deficiency defined as TSAT ≤20% and serum ferritin ≤100 ng/mL in predialysis and peritoneal dialysis patients, or ≤200 ng/mL in hemodialysis patients 6.
Common Pitfalls and Caveats
- Coexisting Deficiencies: ACD frequently coexists with true iron deficiency, making diagnosis challenging 5
- Ferritin Interpretation: As an acute-phase reactant, ferritin can be falsely elevated in inflammatory states even when iron stores are low 4, 1
- Timing of Blood Draws: For hemodialysis patients, hemoglobin should be measured predialysis, as postdialysis levels can be artificially elevated due to hemoconcentration 4
- Incomplete Testing: Using ferritin alone is insufficient; a comprehensive panel including iron studies is essential for accurate diagnosis 5
By following this diagnostic approach and recognizing the characteristic pattern of laboratory findings, clinicians can accurately diagnose anemia of chronic disease and distinguish it from other common anemias.