What is the initial step in the workup of a patient with normocytic anemia?

Workup of Normocytic Anemia

The initial step in evaluating normocytic anemia is obtaining a reticulocyte count to distinguish between decreased red blood cell production (bone marrow failure, chronic disease) and increased destruction or loss (hemolysis, hemorrhage). 1

Initial Laboratory Assessment

The reticulocyte count serves as the critical branching point in your diagnostic algorithm:

• Low or normal reticulocyte count indicates ineffective erythropoiesis from bone marrow disorders, chronic disease, or nutritional deficiencies 1
• Elevated reticulocyte count indicates hemolysis or recent hemorrhage with appropriate marrow response 1

Diagnostic Algorithm Based on Reticulocyte Count

If Reticulocyte Count is Elevated

Proceed with hemolysis evaluation:

• Obtain peripheral blood smear to identify schistocytes and red cell morphology abnormalities 1
• Check hemolysis markers: haptoglobin (decreased), LDH (elevated), and indirect bilirubin (elevated) 1
• Look for clinical signs: jaundice, hepatosplenomegaly 2

If Reticulocyte Count is Low or Normal

Screen systematically for reversible causes:

• Iron studies (serum ferritin, transferrin saturation) should be performed even with normocytic indices, as mixed deficiencies can mask microcytosis 1, 2
• Check MCH alongside MCV, as reduced MCH despite normal MCV indicates concurrent iron deficiency 1
• Renal function tests (creatinine, GFR) are essential, as normocytic anemia develops when creatinine ≥2.0 mg/dL or GFR <30-35 mL/min/1.73m² due to erythropoietin deficiency 1, 2
• Vitamin B12 and folate levels should be checked, as combined deficiency states may result in normal MCV 2
• Inflammatory markers (CRP, ESR) to assess for anemia of chronic inflammation 2
• Stool test for occult blood to investigate gastrointestinal bleeding 2

Important Diagnostic Considerations

Red Cell Distribution Width (RDW)

• Elevated RDW in normocytic anemia suggests mixed nutrient deficiencies and warrants comprehensive iron, B12, and folate assessment 1, 2

Chronic Kidney Disease Context

• When serum creatinine ≥2.0 mg/dL and normocytic anemia is present without other identified causes, EPO deficiency is the likely diagnosis 1, 2
• Serum erythropoietin levels are generally not indicated but can confirm EPO deficiency in this specific context 2

Complete Blood Count Evaluation

• Examine all cell lines (leukocytes, hemoglobin, platelets) to evaluate bone marrow function 2
• Anomalies in two or more cell lines require hematology consultation and may necessitate bone marrow aspiration and biopsy 2

Common Pitfalls to Avoid

• Don't assume normocytic means non-nutritional: Early nutritional deficiencies may initially present as normocytic anemia before morphological changes become apparent 2
• Don't skip iron studies: Combined iron and B12/folate deficiency can result in normal MCV, masking the true deficiency state 2
• Don't confuse anemia of chronic disease with simple normocytic anemia: Chronic inflammation causes functional iron deficiency despite normal iron stores through inflammatory cytokines suppressing erythropoiesis 2
• Don't overlook riboflavin deficiency: Though rare, it can present with normochromic, normocytic anemia and marrow aplasia 2

When to Consider Bone Marrow Examination

Bone marrow aspiration and biopsy should be considered when:

• Unexplained pancytopenia or other cytopenias are present 2
• Noninvasive evaluation fails to identify a correctable cause after systematic workup 3

Note that bone marrow examination is only rarely contributive in isolated normocytic anemia without other cytopenias, and most cases have excellent prognosis even when the cause remains unclear 3