What lab tests should be ordered next in a patient with normocytic anemia and normal iron studies?

Laboratory Tests for Normocytic Anemia with Normal Iron Studies

When a patient presents with normocytic anemia and normal iron studies, the next step should be to order a reticulocyte count to determine if the anemia is due to decreased production or increased destruction/loss of red blood cells. 1, 2

Initial Diagnostic Approach

1. Reticulocyte Count/Index:

   • Low reticulocyte count suggests decreased RBC production (bone marrow dysfunction, anemia of chronic disease, renal insufficiency) 1
   • High reticulocyte count indicates blood loss or hemolysis 1

2. Peripheral Blood Smear:

   • Essential to confirm RBC morphology and identify abnormalities 1
   • Can reveal schistocytes (hemolysis), spherocytes (autoimmune hemolytic anemia), or other diagnostic features

Secondary Tests Based on Reticulocyte Results

If Reticulocyte Count is Low:

• Kidney Function Tests (BUN, Creatinine, GFR)

  • To evaluate for anemia of chronic kidney disease 1
  • Consider erythropoietin level if kidney disease suspected

• Inflammatory Markers:

  • C-reactive protein (CRP) and/or ESR
  • To assess for anemia of chronic inflammation 1, 3

• Complete Metabolic Panel:

  • To evaluate liver function and other organ systems 3

• Thyroid Function Tests (TSH, Free T4):

  • Hypothyroidism can cause normocytic anemia 4

• Vitamin B12 and Folate Levels:

  • Early deficiency can present as normocytic before becoming macrocytic 3
  • Up to 84% of B12-deficient patients may have normal MCV 3

If Reticulocyte Count is High:

• Hemolysis Workup:

  • Lactate dehydrogenase (LDH)
  • Haptoglobin (decreased in hemolysis)
  • Indirect bilirubin 2

• Coombs Test (Direct Antiglobulin Test):

  • To evaluate for autoimmune hemolytic anemia

• Stool Occult Blood Test:

  • To evaluate for gastrointestinal blood loss 1

Additional Tests to Consider

• Bone Marrow Examination:

  • If other tests are inconclusive or if bone marrow failure is suspected 1
  • Particularly important if multiple cell lines are affected (pancytopenia)

• Hemoglobin Electrophoresis:

  • To evaluate for hemoglobinopathies that can present with normocytic anemia

• Erythropoietin Level:

  • Helps distinguish between primary bone marrow disorders and secondary causes 1

Common Pitfalls to Avoid

• Overlooking multiple concurrent causes of anemia - Normocytic anemia may have more than one etiology 3

• Attributing anemia to age alone in older adults - Always search for an underlying cause 3

• Neglecting to investigate mild anemia - Even mild anemia warrants proper evaluation 3

• Missing vitamin B12 deficiency by relying solely on MCV - Early B12 deficiency can present with normal MCV 3

• Failing to consider rare causes such as aplastic anemia or myelodysplastic syndromes in persistent unexplained cases 2

The systematic approach outlined above will help identify the underlying cause of normocytic anemia when iron studies are normal, allowing for appropriate targeted treatment.