Diagnostic Approach to Anemia

Initial Evaluation

The American Society of Nephrology recommends beginning with a complete blood count (CBC) including hemoglobin, red cell indices, white blood cell count with differential, platelet count, and absolute reticulocyte count, followed by iron studies and vitamin B12 and folate levels 1, 2, 3
Hemoglobin is preferred over hematocrit for its better reproducibility across laboratories and lack of influence from sample storage time or patient glucose levels 1
The initial evaluation should include absolute reticulocyte count to assess bone marrow response to anemia, with a low count indicating impaired erythropoiesis and an elevated count suggesting increased red cell production or hemolysis 1, 3

Serum ferritin is the most useful marker for iron stores, with levels <30 μg/L confirming iron deficiency in the absence of inflammation 3
Transferrin saturation (TSAT) values <15-16% support iron deficiency and are less affected by inflammation than ferritin 3
Vitamin B12 and folate levels are essential for evaluating macrocytic anemia and should be obtained in the initial workup 2, 3

Microcytic anemia (MCV < 80 fL) most commonly indicates iron deficiency anemia, which is the most prevalent cause of anemia globally 3
Normocytic anemia (MCV 80-100 fL) may indicate hemorrhage, hemolysis, or anemia of chronic inflammation 3
Macrocytic anemia (MCV > 100 fL) suggests vitamin B12 or folate deficiency 3, 4

Abnormalities in two or more cell lines warrant hematology consultation 1
Bone marrow aspiration and biopsy should be considered when the initial workup is unrevealing or when additional cytopenias are present 4
In adult men and postmenopausal women with confirmed iron deficiency, investigate for gastrointestinal bleeding 1, 3
Ferritin can be falsely elevated in inflammation, chronic disease, malignancy, or liver disease, requiring clinical context for interpretation 3

If iron studies show elevated ferritin with low TSAT, consider anemia of chronic inflammation 3
Treat by addressing the underlying condition; erythropoietin therapy may be considered in specific situations such as chronic kidney disease 3
C-reactive protein measurement can help assess the contribution of inflammation to elevated ferritin 1