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

Initial Workup for Normocytic Anemia

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

Classification Approach

Normocytic anemia (MCV 80-100 fL) requires a systematic evaluation based on the reticulocyte response:

Step 1: Reticulocyte Count Assessment

• Calculate the reticulocyte index (RI) to assess bone marrow response
  • Normal RI: 1.0-2.0
  • Low RI (<1.0): Indicates decreased RBC production
  • High RI (>2.0): Indicates blood loss or hemolysis 2

Step 2: Based on Reticulocyte Response

For Low Reticulocyte Count (Hypoproliferative):

1. Check inflammatory markers (ESR, CRP)

   • If elevated: Consider anemia of chronic disease/inflammation 1
   • If normal: Proceed to next steps

2. Check renal function (BUN, creatinine)

   • If abnormal: Consider anemia of chronic kidney disease 3

3. Check iron studies

   • Serum iron, TIBC, ferritin, transferrin saturation
   • Early iron deficiency may present as normocytic before becoming microcytic 1
   • Iron deficiency: ferritin <30 ng/mL, transferrin saturation <15% 1
   • Anemia of chronic disease: ferritin >100 ng/mL, low/normal TIBC, transferrin saturation <20% 1

4. Check vitamin B12 and folate levels

   • Early deficiencies may present as normocytic before becoming macrocytic 1

5. Check TSH

   • Hypothyroidism can cause normocytic anemia 1

For High Reticulocyte Count (Hemolysis or Blood Loss):

1. Check for signs of hemolysis:

   • LDH, haptoglobin, indirect bilirubin 3
   • If abnormal: Consider hemolytic anemia
   • Direct Coombs test to evaluate for immune-mediated hemolysis

2. Evaluate for blood loss:

   • Occult blood testing
   • History of overt bleeding
   • Consider GI workup if occult blood positive 1

Step 3: If Initial Workup is Inconclusive

• Consider bone marrow examination, particularly when:
  • Anemia is accompanied by other cytopenias
  • Suspicion of primary bone marrow disorder (MDS, aplastic anemia)
  • No clear cause is identified after initial evaluation 1

Common Pitfalls and Caveats

1. Don't miss mixed anemias

   • Multiple causes of anemia can coexist, especially in elderly patients 4
   • A normal MCV can result from the combination of microcytic and macrocytic processes

2. Don't assume normocytic anemia is always benign

   • While some cases of "idiopathic" normocytic anemia may have good prognosis 4, others may represent early stages of serious conditions
   • Unexplained anemia requires follow-up every 6 months 1

3. Don't transfuse based solely on hemoglobin level

   • Transfusions should be limited to patients with severe symptomatic anemia 3
   • Consider risks including alloimmunization, volume overload, and iron overload 1

4. Don't miss early iron deficiency

   • Iron deficiency can initially present as normocytic before becoming microcytic
   • Check ferritin and transferrin saturation even with normal MCV 1

5. Don't attribute anemia to age alone

   • Anemia in elderly patients should still be investigated thoroughly
   • No downward adjustment is made for age >70 years to avoid missing pathological conditions 1

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