From the Guidelines
The initial step in evaluating and managing a patient with normocytic anemia is to obtain a comprehensive medical history and physical examination, focusing on identifying potential causes such as acute or chronic blood loss, hemolysis, bone marrow disorders, chronic disease, or medication effects. This approach is supported by the guidelines for evaluating anemia, which suggest a morphologic and kinetic approach to characterization 1. The morphologic approach categorizes anemia based on the mean corpuscular volume (MCV), with normocytic anemia having an MCV between 80-100 fL, and may be caused by hemorrhage, hemolysis, bone marrow failure, anemia of chronic inflammation, or renal insufficiency.
Key steps in the workup of normocytic anemia include:
- Complete blood count (CBC) with differential to confirm the diagnosis and assess for other abnormalities
- Reticulocyte count to determine if the anemia is due to decreased production or increased destruction/loss of red blood cells
- Peripheral blood smear to evaluate for morphological abnormalities
- Iron studies, including serum iron, total iron binding capacity (TIBC), and ferritin, to assess for iron deficiency
- Vitamin B12 and folate levels to evaluate for deficiencies
- Kidney and liver function tests to assess for underlying organ dysfunction
- Hemolysis markers, such as lactate dehydrogenase (LDH), haptoglobin, and bilirubin, to evaluate for hemolysis
The differential diagnosis for normocytic anemia is broad and includes:
- Acute or chronic blood loss
- Hemolysis due to autoimmune disorders, infections, or medications
- Bone marrow disorders, such as aplastic anemia or myelodysplastic syndromes
- Chronic disease, such as chronic kidney disease or rheumatoid arthritis
- Medication effects, such as those caused by certain antibiotics or anti-inflammatory agents
Treatment of normocytic anemia depends on the underlying cause, and may include iron supplementation, erythropoietin for chronic kidney disease-related anemia, or addressing the primary condition causing the anemia 1. In patients with cancer, erythropoiesis-stimulating agents (ESAs) may be considered for the treatment of anemia, but only after correction of iron deficiency and other underlying causes, and with careful consideration of the risks and benefits 1.
From the Research
Differential Diagnosis for Normocytic Anemia
- Anemia of inflammation 2
- Hemolytic anemia 2, 3
- Anemia of chronic kidney disease 2
- Acute blood loss anemia 2
- Aplastic anemia 2
- Nutritional deficiencies 4
- Malignancy (solid tumors or hematologic cancer) 4
- Rheumatologic disorders 4
- Endocrine disorders 4
- Other systemic diseases 4
Initial Workup for Normocytic Anemia
- Complete blood count (CBC) 3, 5, 6
- Reticulocyte count 2, 3, 5, 6
- Peripheral blood smear 3, 6
- Iron panel (ie, ferritin and iron levels, total iron-binding capacity, transferrin saturation) 6
- Levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin 6
- Examination of the mean corpuscular volume to categorize the anemia as microcytic, macrocytic, or normocytic 3