What is the initial work-up for a patient with normocytic anemia?

Initial Workup for Normocytic Anemia

The initial workup for normocytic anemia should include a complete blood count with indices, peripheral blood smear review, and reticulocyte count to determine the underlying cause, followed by targeted second-line testing based on the reticulocyte index. 1

First-Line Assessment

• Complete blood count (CBC) with indices to confirm the normocytic nature (MCV 80-100 fL) of the anemia and identify any other cytopenias 1, 2
• Visual review of the peripheral blood smear to confirm red cell morphology and identify abnormalities 1, 2
• Reticulocyte count corrected for the degree of anemia (reticulocyte index) to evaluate bone marrow response 1, 3
• Detailed history and physical examination focusing on symptoms of anemia (fatigue, dyspnea, headache, vertigo), potential blood loss, and signs of underlying causes (jaundice, splenomegaly, neurologic symptoms) 2

Second-Line Testing Based on Reticulocyte Index

For Low Reticulocyte Index (<1.0) - Decreased Production

• Iron studies: serum ferritin, serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT) 1, 2
• Renal function tests: serum creatinine and BUN to assess for chronic kidney disease 1, 2
• Inflammatory markers: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) 1
• Endocrine function tests: thyroid function tests (TSH, free T4) 1
• Nutritional assessment: vitamin B12 and folate levels 1, 3
• Consider bone marrow examination if other tests are inconclusive, especially in older patients or when myelodysplastic syndrome is suspected 1, 4

For High Reticulocyte Index (>2.0) - Increased Destruction/Loss

• Hemolysis workup: lactate dehydrogenase (LDH), haptoglobin, and indirect bilirubin 1, 5
• Blood loss assessment: stool guaiac test for occult blood and menstrual history in women 1, 2
• Coombs test to evaluate for immune-mediated hemolysis 3

Common Causes of Normocytic Anemia

• Anemia of chronic disease/inflammation: characterized by low serum iron, low TIBC, normal/elevated ferritin, and low TSAT 1, 6
• Chronic kidney disease: develops when GFR falls below 20-30 ml/min due to erythropoietin deficiency 1, 2
• Acute blood loss: requires assessment for bleeding sources 5
• Hemolytic anemia: identified by increased reticulocyte count, elevated LDH, decreased haptoglobin 5, 3
• Bone marrow disorders: including aplastic anemia and myelodysplastic syndromes 1, 4
• Drug-induced anemia: review medication history for potential causative agents 6

Special Considerations

• In patients with cancer, anemia may be due to bone marrow infiltration, chronic inflammation, or treatment effects 2
• Multiple myeloma should be considered, especially in older patients with unexplained anemia 2
• "Idiopathic" normocytic anemia is more common in elderly patients and often has a benign course 4
• Bone marrow examination should be reserved for cases where initial workup is inconclusive or when malignancy is suspected 1, 4

Pitfalls to Avoid

• Mistaking anemia of chronic disease for iron deficiency anemia and inappropriately treating with iron supplements 6
• Failing to correct the reticulocyte count for the degree of anemia, which may lead to misinterpretation of bone marrow response 3
• Overlooking drug-induced causes of normocytic anemia 6
• Performing unnecessary bone marrow examination when non-invasive testing could identify the cause 4
• Missing early megaloblastic anemia, which can initially present as normocytic before developing macrocytosis 3