Diagnostic Approach to Anemia

Initial Evaluation

The initial workup for anemia should include a complete blood count (CBC) with red cell indices, absolute reticulocyte count, serum ferritin, transferrin saturation (TSAT), and vitamin B12 and folate levels, as recommended by clinical guidelines 1, 2
Hemoglobin concentration is the preferred measure over hematocrit due to better reproducibility across laboratories and lack of influence from sample storage time or patient glucose levels 2
Mean corpuscular volume (MCV) classifies anemia into three categories: microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL) 1, 2

Serum ferritin is the single most useful marker for iron stores, with levels <30 μg/L confirming iron deficiency in the absence of inflammation 1, 2
Transferrin saturation (TSAT) values <15-16% support iron deficiency and are less affected by inflammation than ferritin 1, 2

Absolute reticulocyte count assesses bone marrow response to anemia 3, 1, 2
A low or normal reticulocyte count indicates impaired erythropoiesis (production problem) 1
An elevated reticulocyte count suggests increased red cell production in response to hemolysis or blood loss 1, 2

Vitamin B12 and folate levels are essential for evaluating macrocytic anemia and should be obtained in the initial workup 3, 1, 2

Haptoglobin, lactate dehydrogenase (LDH), and bilirubin are necessary when hemolysis is suspected 1
Direct antiglobulin testing (Coombs test) for patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or history of autoimmune disease 4, 5
Thyroid-stimulating hormone (TSH) when indicated 4, 5
Hemoglobin electrophoresis if hemoglobinopathies like thalassemia trait are suspected, particularly in patients with appropriate ethnic background 1

Do not accept ferritin alone in patients with inflammation; use TSAT to confirm iron deficiency 1, 2
Do not stop at finding one abnormality in the upper GI tract without investigating the colon, as dual pathology occurs in 10-15% of patients 6
Do not overlook dietary history, but do not presume borderline deficient diets as the sole cause without full investigation 6
Do not delay hematology consultation when abnormalities in two or more cell lines are present 2