Approach to Differentiating Anemias Based on CBC

Initial Classification by MCV

The American College of Physicians suggests that microcytic anemia is most commonly caused by iron deficiency anemia, with other causes including thalassemia, anemia of chronic disease, and sideroblastic anemia 1, 2
High RDW suggests iron deficiency, while normal RDW is more consistent with thalassemia, according to the European Hematology Association 3, 4
The National Comprehensive Cancer Network recommends follow-up testing, including serum ferritin, transferrin saturation, and CRP, to confirm iron deficiency 3
Serum ferritin <30 μg/L confirms iron deficiency in the absence of inflammation, as stated by the American Society of Hematology 3

A low reticulocyte index (RI < 1.0) indicates decreased RBC production, suggesting iron deficiency, vitamin B12/folate deficiency, aplastic anemia, or bone marrow dysfunction, according to the National Comprehensive Cancer Network 1, 2
A normal or high reticulocyte index (RI > 2.0) indicates normal or increased RBC production, suggesting blood loss or hemolysis in anemic patients, as recommended by the American College of Physicians 1, 2

For microcytic anemia, iron studies, including serum iron, TIBC, and transferrin saturation, can help confirm iron deficiency, as suggested by the European Hematology Association 1
For normocytic anemia, reticulocyte count is the key follow-up test, and if reticulocytes are low, evaluation for renal disease, chronic inflammation, or bone marrow disorders is necessary, according to the National Institute of Diabetes and Digestive and Kidney Diseases 3
For macrocytic anemia, vitamin B12 and folate levels, as well as liver function tests and thyroid studies, can help identify the underlying cause, as recommended by the American Society of Hematology 1, 5