What is the initial step in evaluating anaemia?

Initial Evaluation of Anaemia

The initial step in evaluating anaemia is to obtain a complete blood count (CBC) with red cell indices, followed immediately by assessment of iron status (serum ferritin and transferrin saturation) and reticulocyte count. 1, 2

Primary Laboratory Tests

Complete Blood Count with Indices

• Hemoglobin measurement is preferred over hematocrit because it has superior reproducibility across laboratories, lower coefficients of variation, and is not affected by sample storage time or patient variables like serum glucose 1
• The CBC evaluates all three cell lines (white blood cells, hemoglobin, and platelets) to assess overall bone marrow function 1
• Mean corpuscular volume (MCV) provides the critical first classification: microcytic (<80 fL), normocytic (80-100 fL), or macrocytic (>100 fL) 2, 3
• Abnormalities in two or more cell lines warrant hematology consultation, as this suggests bone marrow pathology rather than isolated anaemia 1

Iron Studies

• Serum ferritin and transferrin saturation must be obtained in the initial workup because iron deficiency is the most common cause of anaemia and frequently coexists with other conditions 1, 4
• Ferritin <30 μg/L is the most specific marker for iron deficiency in the absence of inflammation 2
• Transferrin saturation <15% with elevated total iron binding capacity indicates iron deficiency 2

Reticulocyte Count

• The reticulocyte count (absolute or reticulocyte index adjusted for degree of anaemia) determines whether bone marrow is responding appropriately 1
• Low reticulocyte count indicates inadequate erythropoiesis from nutritional deficiencies, bone marrow dysfunction, or insufficient erythropoietin 1
• Elevated reticulocyte count suggests blood loss or hemolysis and requires different diagnostic pathways 2, 3

Secondary Tests Based on Initial Results

If Microcytic (MCV <80 fL)

• Confirm iron studies already obtained 2
• Consider hemoglobin electrophoresis if thalassemia suspected (family history, ethnicity, normal iron studies) 2

If Macrocytic (MCV >100 fL)

• Measure vitamin B12 and folate levels 1, 2
• Consider methylmalonic acid and homocysteine if B12 deficiency suspected but serum level borderline 2

If Normocytic with Low Reticulocyte Count

• Evaluate kidney function (creatinine, estimated GFR) to assess for chronic kidney disease 1, 5
• Consider inflammatory markers (CRP, ESR) for anaemia of chronic disease 2, 5

If Elevated Reticulocyte Count

• Obtain hemolysis workup: lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, direct Coombs test 2, 6
• Examine peripheral blood smear for schistocytes, spherocytes, or other abnormal morphology 2, 3

Critical Pitfalls to Avoid

• Ferritin is an acute phase reactant and may be falsely elevated in inflammatory states despite true iron deficiency; if ferritin is 30-100 μg/L with inflammation present, iron deficiency may still exist 1, 2, 5
• Mixed anaemias can present with normal MCV when microcytosis and macrocytosis coexist (e.g., combined iron and B12 deficiency); always review the red cell distribution width (RDW) 2
• Low MCV typically suggests iron, folate, or B12 deficiency, but can also indicate inherited hemoglobin synthesis disorders 1
• In non-dialysis CKD patients not on erythropoietic agents, finding iron deficiency should prompt evaluation for gastrointestinal bleeding 1

Special Population Considerations

Standard hemoglobin thresholds for defining anaemia may not apply to: 1, 2

• Pregnant or menstruating women
• Individuals living at high altitude
• Smokers
• Men aged ≥70 years
• Non-Caucasian populations
• Patients with chronic lung disease or hemoglobinopathies

Algorithmic Approach Summary

1. Order CBC with indices, iron studies (ferritin, transferrin saturation), and reticulocyte count simultaneously 1, 2, 3
2. Classify by MCV: microcytic, normocytic, or macrocytic 2, 3
3. Assess reticulocyte response: low/normal (production problem) vs. elevated (loss/destruction) 1, 2
4. Pursue targeted testing based on the combination of MCV and reticulocyte findings 2, 3
5. Examine peripheral blood smear when morphology may provide diagnostic clues 2, 3, 7