Basic Approach to Abnormal FBC: Part I (RBC Indices)

by Dr. Carol Moore, MBChB (UCT), MMed in Haematopathology (University of Stellenbosch)

PATHCHAT Edition No. 9
Please contact your local Ampath pathologist for more information.

Understanding Full Blood Count (FBC) Results

FBC results should always be interpreted in the context of:

• The patient’s normal baseline (5% of the population may have values outside the reference range).
• Sex differences (RBC levels are generally lower in women).
• Racial variations (individuals of African descent tend to have lower haemoglobin (Hb) levels than those of Caucasian ancestry).

Key Parameters to Evaluate in FBC:

1. Haemoglobin (Hb)
2. Mean Cell Volume (MCV) – critical for anaemia classification.
3. Red Blood Cell (RBC) Count
4. Red Cell Distribution Width (RDW)

Approach to Anaemia (Low Hb Levels)

The first step in diagnosing anaemia is to classify it based on MCV (Mean Cell Volume):

• Microcytic anaemia (low MCV)
• Normocytic anaemia (normal MCV)
• Macrocytic anaemia (high MCV)

A peripheral blood (PB) smear evaluation can further help guide diagnosis and suggest additional testing.

1. Microcytic Anaemia (Low MCV)

🔹 Main Causes:

• Iron deficiency anaemia (most common).
• Thalassaemia.
• Anaemia of chronic disease (ACD).

🔹 Recommended Initial Investigation:

• Serum ferritin level.

Interpreting Results:

• Low ferritin → Confirms iron deficiency anaemia.
• Normal or raised ferritin → Suggests thalassaemia or ACD.

🔹 Differentiating Between Causes:

• Thalassaemia:
  • Long-standing microcytosis.
  • Positive family history.
  • High RBC count.
  • Abnormal RBC morphology → Perform Hb electrophoresis.
• Anaemia of chronic disease (ACD):
  • Normal RDW.
  • Unremarkable RBC morphology.
  • Further testing depends on patient history and PB smear findings.

2. Normocytic Anaemia (Normal MCV)

🔹 Step 1: Check Reticulocyte Count

Interpreting Results:

• High reticulocyte count → Suggests blood loss or haemolysis.
  • Next steps: Patient history, faecal occult blood test, PB smear review, haemolysis screen.
• Low reticulocyte count → Suggests reduced RBC production.
  • Next steps: Identify common treatable causes (renal failure, nutritional deficiencies, chronic disease, or bone marrow disorders).

🔹 Possible Causes:

• Anaemia of chronic disease (ACD).
• Renal failure (decreased erythropoietin production).
• Primary bone marrow disorders (myelodysplastic syndromes, aplastic anaemia).

3. Macrocytic Anaemia (High MCV)

🔹 Step 1: Measure Vitamin B12 and Folate Levels

Interpreting Results:

• Low B12 or folate → Confirms deficiency → Investigate underlying causes (e.g., malabsorption, dietary deficiency, pernicious anaemia).
• Normal B12/folate → Consider other causes (drugs, alcohol, liver disease, haemolysis).

🔹 Further Steps if B12/Folate Deficiency is Excluded:

• Obtain detailed medication and alcohol history.
• Perform liver function tests (LFTs) and reticulocyte count.
• If still unexplained, consider myelodysplastic syndrome or other bone marrow disorders → Perform PB smear review.

Approach to Polycythaemia (Increased Hb & Hct Levels)

🔹 Possible Causes:

1. False elevation due to reduced plasma volume (e.g., dehydration, smoking, diuretics).
2. True polycythaemia due to increased RBC mass:
   • Primary polycythaemia: Polycythaemia Vera (PV) (a clonal myeloproliferative disorder).
   • Secondary polycythaemia: Driven by erythropoietin (EPO).

🔹 Step 1: Confirm Elevated Hb/Hct on a Fresh Blood Sample

🔹 Step 2: Identify Secondary Causes (if present):

• History and clinical examination may reveal causes such as:
  • Chronic hypoxia (cardiac/pulmonary disease).
  • Tumours producing erythropoietin (renal carcinoma, hepatocellular carcinoma).
  • High-altitude exposure.

🔹 Step 3: Perform JAK-2 Mutation Testing & Serum Erythropoietin (EPO) Levels

Interpreting Results:

• JAK-2 mutation positive + Low/normal EPO → Suggests Polycythaemia Vera (PV).
• JAK-2 mutation negative + High EPO → Suggests Secondary polycythaemia (further workup needed).
• JAK-2 negative + Normal EPO → Consider familial erythrocytosis or unclassifiable myeloproliferative neoplasm.

🔹 Step 4: Bone Marrow Biopsy (if necessary)

• To confirm Polycythaemia Vera (PV) or rule out other myeloproliferative disorders.

Key Takeaways & Next Steps

Anaemia Workup Summary:

1. Classify anaemia by MCV (microcytic, normocytic, macrocytic).
2. Use ferritin, reticulocyte count, B12/folate tests to determine cause.
3. Perform PB smear review for morphological clues.
4. Investigate underlying conditions and consider bone marrow biopsy if needed.

Polycythaemia Workup Summary:

1. Confirm true polycythaemia vs. dehydration.
2. Assess clinical history for secondary causes.
3. Perform JAK-2 mutation and EPO level testing.
4. Consider bone marrow biopsy if primary PV is suspected.