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

Normocytic Anemia Workup

The initial workup for normocytic anemia should begin with a reticulocyte count to distinguish between decreased RBC production (low reticulocyte count) and increased destruction or loss (high reticulocyte count), followed by targeted testing based on this result. 1

Initial Laboratory Assessment

Step 1: Confirm Normocytic Anemia and Check Reticulocyte Count

• Verify MCV is 80-100 fL on complete blood count 1
• Obtain reticulocyte count immediately—this is the critical branch point 1, 2
• Examine peripheral blood smear for morphologic clues 3
• Check red cell distribution width (RDW): elevated RDW in normocytic anemia suggests underlying iron deficiency or combined deficiency states 1

Step 2A: Low Reticulocyte Count (Decreased Production)

A low reticulocyte count indicates bone marrow failure, nutritional deficiency, or chronic disease 1. Order:

• Iron studies: serum ferritin, transferrin saturation, and serum iron 1
• Vitamin B12 and folate levels: early nutritional deficiencies may present as normocytic before MCV changes 1
• Inflammatory markers: CRP and ESR to assess for anemia of chronic inflammation 1
• Renal function tests: creatinine and estimated GFR, as chronic kidney disease commonly causes normocytic anemia 1, 2, 4
• Thyroid function tests: hypothyroidism can cause normocytic anemia 5

Step 2B: High Reticulocyte Count (Increased Production)

A high reticulocyte count indicates hemolysis or acute blood loss 1, 2. Order:

• Hemolysis workup:
  • Indirect (unconjugated) bilirubin 2
  • Haptoglobin (decreased in hemolysis) 2
  • Lactate dehydrogenase (LDH) 2
  • Direct antiglobulin test (Coombs test) 3
• Assess for bleeding: stool guaiac, history of melena/hematochezia, menstrual history 5
• Physical examination for jaundice, hepatosplenomegaly 2

Common Causes by Category

Decreased Production (Low Reticulocyte Count)

• Anemia of chronic inflammation: most common in older adults; ferritin normal or elevated despite functional iron deficiency 1, 2
• Chronic kidney disease: develops when GFR drops below 20-30 mL/min due to inadequate erythropoietin production 4
• Early nutritional deficiencies: iron, B12, or folate deficiency before morphologic changes appear 1
• Combined deficiency states: simultaneous iron and B12/folate deficiency can normalize MCV 1
• Aplastic anemia: requires bone marrow evaluation 2
• Myelodysplastic syndrome: consider in older adults with unexplained anemia 5

Increased Destruction/Loss (High Reticulocyte Count)

• Acute hemorrhage: focus on identifying and stopping bleeding source 2
• Hemolytic anemia: autoimmune, drug-induced, or hereditary causes 2, 3

Critical Pitfalls to Avoid

• Do not assume normocytic anemia excludes nutritional deficiency: early iron, B12, or folate deficiency may present with normal MCV before morphologic changes develop 1
• Combined deficiencies mask each other: simultaneous iron and B12/folate deficiency can result in normal MCV despite significant deficiency 1
• Functional iron deficiency in inflammation: patients with chronic inflammation may have normal or elevated ferritin but still require iron supplementation 1
• Riboflavin deficiency: rare but presents as normocytic anemia with marrow aplasia; consider in patients with poor nutrition 1

Special Considerations

Chronic Kidney Disease

• Normocytic anemia develops when GFR falls below 20-30 mL/min 4
• Erythropoietin deficiency is the primary cause 4
• Do not initiate erythropoiesis-stimulating agents until hemoglobin is below 10 g/dL in asymptomatic patients 2

Older Adults

• Anemia is associated with increased morbidity and mortality 5
• Common causes include nutritional deficiency, chronic kidney disease, chronic inflammation, and occult gastrointestinal blood loss 5
• If iron deficiency is confirmed, endoscopy is warranted to evaluate for gastrointestinal malignancy 5

Acute Management

• Symptomatic patients with hemoglobin ≤8 g/dL may require blood transfusion 5
• For acute blood loss with hemodynamic instability, initiate mass transfusion protocol 2
• Initial resuscitation should use crystalloid fluids, not blood products 2

When to Consider Bone Marrow Evaluation

Consider bone marrow aspiration and biopsy when:

• Unexplained pancytopenia or other cytopenias 6
• Suspected aplastic anemia or myelodysplastic syndrome 2, 5
• Persistent anemia without clear etiology after initial workup 5
• Abnormal peripheral smear findings suggesting marrow pathology 3