Recommended Laboratory Tests for Anemia Evaluation
Begin with a complete blood count (CBC) with differential, serum ferritin, and transferrin saturation as your minimum initial workup for any patient with suspected anemia. 1, 2
Core Initial Laboratory Panel
The following tests form the essential foundation for anemia evaluation:
Complete Blood Count (CBC) with differential: Measure hemoglobin (preferred over hematocrit due to better reproducibility), white blood cells, platelets, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW). 1, 2
Reticulocyte count: Essential to assess bone marrow response to anemia. A low or inappropriately normal count suggests defective red cell production or deficiencies, while an elevated count points toward hemolysis or blood loss. 1, 2
Serum ferritin: The single most useful marker for iron stores. In patients without inflammation, ferritin <30 μg/L confirms iron deficiency. 1, 2
Transferrin saturation (TSAT): More reliable than ferritin when inflammation is present, as it is less affected by acute-phase reactions. TSAT <16-20% indicates inadequate iron availability for erythropoiesis. 1, 2
C-reactive protein (CRP): Necessary to interpret ferritin levels correctly, as ferritin acts as an acute-phase reactant and can be falsely elevated in inflammatory states. 1
Interpretation Based on Initial Results
When ferritin is <30 μg/L without inflammation: This confirms absolute iron deficiency. 1, 2
When ferritin is 30-100 μg/L with inflammation present: Iron deficiency may still exist despite seemingly "normal" ferritin levels. This represents a combination of true iron deficiency and anemia of chronic disease. 1, 2
When ferritin is >100 μg/L with TSAT <20%: This pattern indicates anemia of chronic disease. 1
When MCV is low (<80 fL): Consider iron deficiency, thalassemia, or inherited hemoglobin synthesis disorders. Also check vitamin B12 and folate, as combined deficiencies can mask each other. 1
When MCV is elevated (>100 fL): Measure vitamin B12 and folate levels, and consider medication effects (particularly thiopurines), alcohol use, hypothyroidism, or reticulocytosis. 1
When abnormalities exist in two or more cell lines: Consult hematology, as this suggests bone marrow dysfunction requiring more extensive evaluation. 1
Extended Workup When Initial Tests Are Inconclusive
Add these tests when the cause of anemia remains unclear after the core panel:
Vitamin B12 and folate levels: Particularly important in macrocytic anemia or when MCV is normal despite suspected combined deficiencies. 1, 2
Haptoglobin and lactate dehydrogenase (LDH): To evaluate for hemolysis when reticulocyte count is elevated. 1
Stool guaiac test for occult blood: Essential in iron deficiency anemia, especially in non-menstruating patients, to identify gastrointestinal bleeding. 2
Critical Pitfalls to Avoid
Do not rely on ferritin alone in patients with inflammation, infection, or chronic disease. Ferritin can be falsely elevated despite true iron deficiency because it functions as an acute-phase reactant. Always interpret ferritin in conjunction with CRP and TSAT. 1, 2
Do not assume hemoglobin and hematocrit alone are sufficient. These are late indicators of iron deficiency and will miss early iron depletion states. Many patients with normal CBC parameters have depleted iron stores on ferritin testing. 1
Do not overlook the timing of blood draws in dialysis patients. Use predialysis hemoglobin measurements for accurate assessment. 1
Do not misinterpret normal MCV as excluding iron deficiency. When microcytosis and macrocytosis coexist (such as combined iron and B12 deficiency), they can neutralize each other, resulting in falsely normal MCV. An elevated RDW provides the clue in this situation. 1
Special Population Considerations
In chronic kidney disease patients: Consider percent hypochromic red blood cells (PHRBC) and reticulocyte hemoglobin content (CHr) if available, as these have superior sensitivity and specificity for functional iron deficiency compared to standard markers. However, these tests require specialized equipment and are not widely available. 1
In inflammatory bowel disease patients: Screen regularly with CBC, CRP, and ferritin. Use the higher ferritin threshold of 100 μg/L to define iron deficiency in the presence of active inflammation. 1
When iron deficiency is confirmed but no obvious source exists: Pursue endoscopic evaluation, particularly in men and postmenopausal women, as gastrointestinal bleeding is a common occult cause. 2