What is the workup for normochromic (having a normal amount of hemoglobin) normocytic (having normal sized red blood cells) anemia?

Workup for Normochromic Normocytic Anemia

The comprehensive workup for normochromic normocytic anemia should begin with a complete blood count (CBC) with indices, reticulocyte count, peripheral blood smear examination, and basic iron studies, followed by targeted testing based on these initial results to identify the underlying cause. 1

Initial Assessment

• Complete blood count (CBC) with indices to determine if other cytopenias are present and confirm the normocytic (MCV 80-100 fL) and normochromic nature of the anemia 1
• Visual review of the peripheral blood smear to confirm red cell morphology and identify abnormalities 1
• Reticulocyte count corrected for the degree of anemia (reticulocyte index [RI]) to assess bone marrow response 1
  • Low RI (<1.0): indicates decreased RBC production (most common in normocytic anemia)
  • High RI (>2.0): indicates blood loss or hemolysis

Second-Line Testing Based on Reticulocyte Index

For Low Reticulocyte Index (Decreased Production):

1. Iron Studies 1:

   • Serum ferritin (stores)
   • Serum iron and total iron binding capacity (TIBC)
   • Transferrin saturation (TSAT)
   • Consider percent hypochromic red cells if available

2. Renal Function 1, 2:

   • Serum creatinine and BUN
   • eGFR calculation
   • Normocytic anemia is common when GFR drops below 20-30 ml/min

3. Inflammatory Markers 1:

   • C-reactive protein (CRP)
   • Erythrocyte sedimentation rate (ESR)

4. Endocrine Function 1:

   • Thyroid function tests (TSH, free T4)

5. Nutritional Assessment 1:

   • Vitamin B12 and folate levels
   • Consider homocysteine and methylmalonic acid if B12 deficiency is suspected

6. Bone Marrow Evaluation 3:

   • Consider if diagnosis remains unclear after above testing
   • Not routinely needed in most cases of normocytic anemia

For High Reticulocyte Index (Increased Destruction/Loss):

1. Hemolysis Workup 1:

   • Lactate dehydrogenase (LDH)
   • Haptoglobin
   • Indirect bilirubin
   • Direct Coombs test

2. Blood Loss Assessment 1:

   • Stool guaiac test for occult blood
   • Consider endoscopic evaluation if GI blood loss suspected
   • Menstrual history in women

Special Considerations

Anemia of Chronic Disease/Inflammation

• Often presents as normocytic anemia 1, 4
• Characterized by low serum iron, low TIBC, normal/elevated ferritin, and low TSAT 1
• Look for underlying chronic conditions (infection, autoimmune disease, malignancy) 4

Chronic Kidney Disease

• Normocytic anemia develops when GFR falls below 20-30 ml/min 5
• Primarily due to erythropoietin deficiency 1, 5
• Iron studies may show functional iron deficiency 1

Cancer-Related Anemia

• May be due to bone marrow infiltration, chronic inflammation, or treatment effects 1
• Consider PET/CT or other imaging if malignancy suspected 1

Myelodysplastic Syndromes

• Consider in older patients with unexplained normocytic anemia 1
• May require bone marrow examination for diagnosis 1

Common Pitfalls to Avoid

• Missing mixed anemias: A normocytic picture can result when microcytosis (iron deficiency) and macrocytosis (B12/folate deficiency) coexist 1
• Overlooking early iron deficiency: Iron deficiency initially presents as normocytic before becoming microcytic 1
• Assuming all normocytic anemias are due to chronic disease: Always complete a thorough workup to identify potentially treatable causes 3, 4
• Relying solely on ferritin for iron status: In inflammatory states, ferritin may be elevated despite iron deficiency; use transferrin saturation and other parameters 1
• Failing to consider medication effects: Many drugs can cause normocytic anemia through various mechanisms 6, 4

By following this systematic approach, the underlying cause of normochromic normocytic anemia can be identified in most patients, allowing for appropriate targeted treatment.