What is the initial workup for a patient presenting with normocytic anemia?

Initial Workup for Normocytic Anemia

The initial workup for a patient presenting with normocytic anemia should include a complete blood count (CBC) with indices, peripheral blood smear examination, and reticulocyte count to determine the underlying cause. 1

First-Line Assessment

• Complete blood count (CBC) with indices to confirm the normocytic (MCV 80-100 fL) nature of the anemia and identify if other cytopenias are present 1
• Peripheral blood smear examination to evaluate red cell morphology and identify abnormalities 1
• Reticulocyte count corrected for the degree of anemia (reticulocyte index) to assess bone marrow response 1, 2
• Based on the reticulocyte index, anemia can be classified as either decreased production (low reticulocyte index <1.0) or increased destruction/loss (high reticulocyte index >2.0) 1, 3

Second-Line Testing Based on Reticulocyte Index

For Low Reticulocyte Index (Decreased Production)

• Iron studies: serum ferritin, serum iron, total iron binding capacity (TIBC), and transferrin saturation (TSAT) 1, 4
• Renal function tests: serum creatinine and BUN to assess for chronic kidney disease 1, 4
• Inflammatory markers: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) 1
• Thyroid function tests: TSH and free T4 to evaluate for hypothyroidism 1
• Vitamin B12 and folate levels to rule out deficiencies that may initially present as normocytic before becoming macrocytic 1, 5

For High Reticulocyte Index (Increased Destruction/Loss)

• Hemolysis workup: lactate dehydrogenase (LDH), haptoglobin, and indirect bilirubin 1, 3
• Blood loss assessment: stool guaiac test for occult blood and menstrual history in women 1
• If hemolysis is suspected, additional tests may include direct antiglobulin test (Coombs test), glucose-6-phosphate dehydrogenase (G6PD) levels, and hemoglobin electrophoresis 3

Special Considerations

Anemia of Chronic Disease/Inflammation

• Most common cause of normocytic anemia 5
• Laboratory findings typically show low serum iron, low TIBC, normal/elevated ferritin, and low TSAT 1
• Look for underlying chronic conditions such as infections, autoimmune disorders, or malignancies 4

Chronic Kidney Disease

• Normocytic anemia develops when GFR falls below 20-30 ml/min due to erythropoietin deficiency 1
• Iron studies may show functional iron deficiency despite adequate stores 1, 4

Cancer-Related Anemia

• Consider bone marrow infiltration, chronic inflammation, or treatment effects 4
• The myelosuppressive effects of cytotoxic agents accumulate over repeated cycles of therapy 4
• The rate of anemia can increase from 19.5% in cycle 1 to 46.7% by cycle 5 of chemotherapy 4

Myelodysplastic Syndromes

• Should be considered in older patients with unexplained normocytic anemia 1
• Bone marrow examination may be required for diagnosis 1

When to Consider Bone Marrow Examination

• Unexplained cytopenias in other cell lines (leukopenia, thrombocytopenia) 6
• Suspicion of myelodysplastic syndrome or other bone marrow disorders 1
• Failure to identify cause after initial workup 6

Common Pitfalls to Avoid

• Mistaking anemia of chronic disease for iron deficiency anemia and inappropriately treating with iron supplements 7
• Overlooking drug-induced causes, which are among the most common causes of normocytic anemia 7
• Performing unnecessary bone marrow examination when a noninvasive workup would be sufficient 6
• Failing to correct the reticulocyte count for the degree of anemia, which can lead to misclassification 1, 2

By following this systematic approach, clinicians can efficiently identify the underlying cause of normocytic anemia and implement appropriate treatment strategies focused on addressing the root cause rather than just treating the anemia itself.