A Practical Approach to Diagnosing Anemia

Initial Evaluation

Anemia, defined as hemoglobin <13 g/dL in men and <12 g/dL in women, is a common clinical finding. Start with a complete blood count (CBC), reticulocyte count, and peripheral smear to classify anemia by mechanism: blood loss, decreased production, or increased destruction.

Microcytic Anemia

The differential includes iron deficiency, thalassemia, and anemia of chronic disease. Serum ferritin is the best initial test—low ferritin confirms iron deficiency, while high/normal may suggest chronic inflammation or thalassemia. Look for target cells or basophilic stippling on smear for clues.

Normocytic Anemia

Evaluate renal function and thyroid levels. Anemia of chronic disease, CKD, and bone marrow suppression are key considerations. A low reticulocyte index suggests decreased marrow output, prompting further evaluation with iron studies, B12/folate levels, and possibly bone marrow biopsy.

Macrocytic Anemia

Common causes include B12/folate deficiency, alcohol use, and certain medications (e.g., hydroxyurea, antiretrovirals). Elevated MCV >100 fL should trigger testing for methylmalonic acid and homocysteine. A hypersegmented neutrophil on smear supports megaloblastic anemia.

Hemolytic Anemia

Suspect hemolysis with elevated LDH, indirect bilirubin, and low haptoglobin. A positive Coombs test indicates autoimmune hemolysis. Inherited conditions (G6PD deficiency, sickle cell) often require specific tests and genetic counseling.

Summary

A systematic approach to anemia—starting with MCV and reticulocyte count—can quickly narrow the differential. Consider patient age, comorbidities, and symptoms to guide further workup and treatment decisions.