Diagnostic Approach for Microcytic Anemia

Initial Evaluation

The Centers for Disease Control and Prevention recommends immediately ordering peripheral blood smear, red blood cell distribution width (RDW), serum ferritin, iron studies, and complete blood count with reticulocyte index for a patient with low MCV 1, 2
RDW measurement is critical to differentiate causes of microcytic anemia, with low MCV + RDW >14% indicating iron deficiency anemia and low MCV + RDW ≤14% suggesting thalassemia minor 1, 2
Serum ferritin is the most specific indicator of depleted iron stores and should be measured in all cases, with ferritin <30 ng/mL indicating absolute iron deficiency in the absence of inflammation 1, 2
Iron studies, including serum iron, TIBC, and transferrin saturation, are essential, with transferrin saturation <15% with ferritin <30 ng/mL confirming absolute iron deficiency 2
Reticulocyte index assesses bone marrow production capacity, with low RI (<1.0-2.0) indicating decreased RBC production and high RI suggesting blood loss or hemolysis 2

Visual examination of RBC morphology is critical to confirm size, shape, and color, and can reveal other diagnostic clues such as target cells in thalassemia or basophilic stippling in lead poisoning 1, 2

If iron deficiency is excluded, hemoglobin electrophoresis may be ordered to evaluate for thalassemia if RDW is normal or minimally elevated 1
Erythrocyte protoporphyrin concentration may be measured if available, with elevated levels indicating iron-deficient erythropoiesis, lead poisoning, infection, or inflammation 1
Lead level may be checked if clinical suspicion exists, particularly in children or those with occupational exposure 1
Evaluation for chronic disease/inflammation, including C-reactive protein, may be necessary 2

Ferritin interpretation in inflammation requires consideration of transferrin saturation and other markers, as chronic inflammatory conditions can elevate ferritin despite true iron deficiency 1, 2
Multiple causes can coexist, particularly in patients with chronic disease, where both iron deficiency and anemia of chronic disease may be present 2

The diagnostic approach involves confirming low MCV, ordering RDW, ferritin, iron studies, reticulocyte index, and peripheral smear, and interpreting results to diagnose iron deficiency or other causes of microcytic anemia 1, 2