What is the workup for different types of anemia?

Workup for Different Types of Anemia

The initial workup for anemia should include a complete blood count (CBC) with indices, reticulocyte count, and peripheral blood smear examination, followed by targeted testing based on the morphologic classification (microcytic, normocytic, or macrocytic) and reticulocyte response. 1

Initial Evaluation

1. Complete Blood Count (CBC) with indices

   • Hemoglobin/hematocrit levels
   • Mean corpuscular volume (MCV)
   • Red cell distribution width (RDW)
   • Mean corpuscular hemoglobin (MCH)
   • Mean corpuscular hemoglobin concentration (MCHC)

2. Reticulocyte count

   • High: Suggests adequate bone marrow response (hemolysis or blood loss)
   • Low: Suggests inadequate bone marrow response (deficiency states, bone marrow failure)

3. Peripheral blood smear examination

   • Evaluates red cell morphology, white cells, and platelets

Specific Workup Based on MCV Classification

1. Microcytic Anemia (MCV < 80 fL)

• Iron studies:

  • Serum iron
  • Total iron binding capacity (TIBC)
  • Transferrin saturation
  • Ferritin

• Hemoglobinopathy evaluation:

  • Hemoglobin electrophoresis (for thalassemias)
  • HbA2 and HbF quantification

• Key differentiating features:

  Parameter	Iron Deficiency Anemia	Anemia of Chronic Disease	Thalassemia
  MCV	Low	Normal/Low	Low
  Serum iron	Low	Low	Normal
  TIBC	High	Low/Normal	Normal
  Ferritin	< 30 μg/L	> 100 μg/L	Normal
  Transferrin saturation	< 15%	< 20%	Normal
  RDW	Elevated	Normal	Normal

  1

2. Normocytic Anemia (MCV 80-100 fL)

• If reticulocyte count is high:

  • Direct antiglobulin test (Coombs test)
  • Lactate dehydrogenase (LDH)
  • Haptoglobin
  • Bilirubin (total and direct)
  • Consider hemolysis workup

• If reticulocyte count is low:

  • Complete metabolic panel
  • Renal function tests (BUN, creatinine, GFR)
  • Inflammatory markers (ESR, CRP)
  • Thyroid function tests
  • Consider bone marrow examination

3. Macrocytic Anemia (MCV > 100 fL)

• Vitamin deficiency evaluation:

  • Vitamin B12 level
  • Serum folate and RBC folate
  • Homocysteine (improves interpretation of B12 and folate levels)
  • Methylmalonic acid (more specific for B12 deficiency)

• Liver function tests

• Thyroid function tests

• Reticulocyte count

  • If elevated: Consider hemolysis
  • If normal/low: Consider megaloblastic anemia

• Important note: Always measure both B12 and folate levels simultaneously as deficiencies can coexist. Before treating folate deficiency, rule out B12 deficiency first, as treating folate deficiency alone may mask B12 deficiency and precipitate subacute combined degeneration of the spinal cord. 1

Special Considerations

Anemia of Chronic Disease/Inflammation

• Check for underlying inflammatory conditions
• Evaluate inflammatory markers (ESR, CRP)
• Pattern: normal/elevated ferritin, low transferrin saturation, normal MCV, low reticulocyte count 1

Chronic Kidney Disease

• Evaluate renal function (serum creatinine, GFR)
• If GFR <60 mL/min/1.73m², consider nephrology consultation 1

Hemolytic Anemia

• Direct antiglobulin test (DAT)
• LDH, haptoglobin, bilirubin
• Peripheral smear for red cell morphology
• Consider specialized tests based on suspected etiology (G6PD, pyruvate kinase, etc.)

Common Pitfalls to Avoid

1. Relying solely on MCV for classification

   • RDW can help distinguish iron deficiency (elevated) from thalassemia (normal)
   • Mixed deficiencies can result in normal MCV

2. Misinterpreting ferritin levels

   • Ferritin is an acute phase reactant and may be elevated despite iron deficiency
   • Consider the entire clinical picture and all iron indices 1

3. Treating folate deficiency without checking B12

   • Can mask B12 deficiency and lead to neurological complications 1

4. Incomplete workup in elderly patients

   • Consider both upper and lower GI sources of blood loss
   • 1-10% of patients may have significant bleeding from both tracts 1

5. Stopping at the first abnormality

   • Multiple causes of anemia can coexist, especially in elderly patients and those with chronic diseases

By following this systematic approach based on MCV classification and reticulocyte response, clinicians can efficiently diagnose the underlying cause of anemia and initiate appropriate treatment.