Normochromic Normocytic Anemia Workup

Initial Assessment

The American College of Physicians recommends a complete blood count (CBC) with indices to determine if other cytopenias are present and confirm the normocytic (MCV 80-100 fL) and normochromic nature of the anemia 1, 2
A visual review of the peripheral blood smear is necessary to confirm red cell morphology and identify abnormalities 1, 3
The reticulocyte count corrected for the degree of anemia (reticulocyte index [RI]) should be assessed to evaluate bone marrow response 1, 3
A low reticulocyte index (<1.0) indicates decreased RBC production, which is the most common cause of normocytic anemia 4

Iron studies, including serum ferritin, serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT), should be performed to evaluate iron status 1, 5, 6
Renal function tests, such as serum creatinine and BUN, should be conducted to assess for chronic kidney disease, which can cause normocytic anemia when GFR drops below 20-30 ml/min 4, 5, 6
Inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), should be measured to evaluate for chronic inflammation 5, 7
Endocrine function tests, such as thyroid function tests (TSH, free T4), should be performed to assess for hypothyroidism, which can cause normocytic anemia 6
Nutritional assessment, including vitamin B12 and folate levels, should be conducted to evaluate for deficiencies 1, 3, 7

A hemolysis workup, including lactate dehydrogenase (LDH), haptoglobin, and indirect bilirubin, should be performed to evaluate for hemolytic anemia 1, 7
Blood loss assessment, including stool guaiac test for occult blood and menstrual history in women, should be conducted to evaluate for blood loss 1, 2, 5, 6

Anemia of chronic disease/inflammation often presents as normocytic anemia, characterized by low serum iron, low TIBC, normal/elevated ferritin, and low TSAT 7

Normocytic anemia develops when GFR falls below 20-30 ml/min, primarily due to erythropoietin deficiency 4
Iron studies may show functional iron deficiency 4, 5

Cancer-related anemia may be due to bone marrow infiltration, chronic inflammation, or treatment effects 1, 3
Consider PET/CT or other imaging if malignancy is suspected 8

Myelodysplastic syndromes should be considered in older patients with unexplained normocytic anemia 1, 3
Bone marrow examination may be required for diagnosis 9