What is the initial step in the workup of a patient with low hemoglobin (hypochromic anemia)?

Initial Workup for Low Hemoglobin (Hypochromic Anemia)

The initial step in the workup of a patient with low hemoglobin (hypochromic anemia) should be a complete blood count (CBC) with red cell indices, followed by iron studies including serum ferritin, transferrin saturation, red cell distribution width (RDW), and C-reactive protein. 1

Diagnostic Approach

Step 1: Confirm Anemia

• Define anemia based on hemoglobin levels:
  • <13.0 g/dL in adult males 2, 1
  • <12.0 g/dL in adult females 2, 1

Step 2: Classify Anemia Based on Red Cell Indices

• Use Mean Corpuscular Volume (MCV) to categorize:
  • Microcytic anemia (MCV <80 fL) - suggests iron deficiency, thalassemia
  • Normocytic anemia (MCV 80-100 fL) - suggests anemia of chronic disease, renal disease
  • Macrocytic anemia (MCV >100 fL) - suggests vitamin B12/folate deficiency, hypothyroidism 2, 1

Step 3: Specific Testing Based on MCV

For hypochromic (microcytic) anemia:

• Iron profile tests:
  • Serum ferritin (<100 μg/L suggests deficiency)
  • Transferrin saturation (TSAT <20% suggests deficiency)
  • Reticulocyte hemoglobin content (RetHe <29 pg)
  • Percentage of hypochromic cells (>10%) 2, 1

Diagnostic Algorithm for Hypochromic Anemia

1. If ferritin <100 μg/L, TSAT <20%:

   • Diagnosis: Iron deficiency anemia
   • Additional workup: Consider GI evaluation for source of blood loss

2. If ferritin normal/elevated with low TSAT:

   • Diagnosis: Anemia of chronic inflammation/disease
   • Additional workup: Evaluate for underlying inflammatory conditions, check CRP

3. If normal iron studies with microcytosis:

   • Consider hemoglobinopathy (thalassemia)
   • Additional workup: Hemoglobin electrophoresis 2, 1

Important Considerations

• Hemoglobin is a more reliable marker for anemia than hematocrit, with lower coefficients of variation across laboratories 1

• Red cell distribution width (RDW) helps distinguish between different types of microcytic anemia:

  Parameter	Iron Deficiency	Anemia of Chronic Disease	Thalassemia
  MCV	Low (<80 fL)	Low or normal	Very low
  RDW	Elevated	Normal or slightly elevated	Normal

• Predictive factors for anemia severity include:

  • Age (>50 years)
  • Female sex
  • Lower baseline hemoglobin
  • Advanced liver disease/cirrhosis
  • Renal dysfunction (creatinine clearance <80 ml/min) 2

Common Pitfalls to Avoid

1. Failing to distinguish between absolute iron deficiency and functional iron deficiency (normal/high ferritin but low transferrin saturation) in inflammatory states

2. Overlooking mixed deficiencies (iron deficiency with folate or B12 deficiency)

3. Initiating treatment before adequate workup, potentially masking underlying serious conditions

4. Relying solely on MCV without considering RDW and other parameters

5. Missing chronic kidney disease as a cause of anemia (check creatinine/GFR in all patients with anemia) 2, 1

By following this systematic approach to hypochromic anemia, you can efficiently identify the underlying cause and develop an appropriate treatment plan based on the specific etiology.