The CBC is more than just numbers on a report — it’s a snapshot of your patient’s cellular health. It represents the dynamic interplay between peripheral cellular demand and the bone marrow response, mediated by various hormonal, neural and cytokine stimuli. And as a veterinary clinical pathology resident, I’ve come to appreciate the depth of information the humble CBC provides. Let’s break it down and explore how to interpret these values with confidence.

 

 

 

What Makes Up a CBC, and Where Do These Cells Come From?

A CBC evaluates the three major cellular components of blood: red blood cells (RBCs), white blood cells (WBCs), and platelets. But understanding these cells starts with their origins in the bone marrow.

• Red Blood Cells (RBCs): These originate from erythropoietic precursors in the bone marrow, maturing under the influence of erythropoietin (EPO). EPO production ramps up in response to hypoxia, regulated by hypoxia-inducible factors. Immature RBCs, or reticulocytes, are released into circulation, where they complete maturation. While dogs, cats, and pigs readily release reticulocytes into circulation, horses retain them in the marrow, and healthy cattle and goats rarely have circulating reticulocytes.

 

RBC maturation. Image adapted from Veterinary Haematology, A Diagnostic Guide and Colour Atlas, John W. Harvey.

 

• White Blood Cells (WBCs): These include:
  • Neutrophils: Mature from myeloblasts through promyelocytes, myelocytes, metamyelocytes and bands, becoming segmented neutrophils. This process takes 6–9 days, with bone marrow storing ~7x the number of circulating neutrophils.
  • Eosinophils and Basophils: Similar maturation pathways to neutrophils, with lineage distinctions becoming apparent at the myelocyte stage. Interleukin-5 released by activated T-helper cells drives eosinophil maturation.

 

Granulocyte maturation. Image adapted from Veterinary Haematology, A Diagnostic Guide and Colour Atlas, John W. Harvey.

 

• • Lymphocytes: Derived from common lymphoid progenitors. B cells mature in the bone marrow, while T cells migrate to the thymus. Both undergo rigorous selection to ensure self-tolerance; failures here can lead to immune-mediated diseases.

 

• Platelets: Produced by megakaryocytes in the bone marrow, each generating 1,000–3,000 platelets. Their production is stimulated by thrombopoietin (TPO), and their appropriate function is critical for primary haemostasis.

 

What Does My CBC Tell Me?

The CBC provides quantitative data about the blood’s cellular components. Paired with a blood smear, it paints a complete picture of haematological health, offering insights into immune function, oxygen-carrying capacity, clotting ability, and bone marrow activity.

Key Parameters and Their Clinical Significance

1. Red Blood Cell Indices

 

 

 

• RBC Count, Haemoglobin (Hb), and Haematocrit (HCT):
  • HCT and PCV should give a similar result, but they are obtained differently. HCT is calculated by the analyser as ([RBC x MCV] / 10) and is therefore susceptible to artifacts affecting these indices (see below). PCV is the direct measure of the packed RBC fraction and is performed manually. This will still be affected by haemolysis (due to loss of the cells you are counting!)
  • These values indicate whether anaemia is present. HCT is typically ~3x Hb, and any mismatches exceeding 5% will be picked up and explored by your pathologist. Discrepancies are often caused by sample interference (e.g., lipemia or haemolysis).
  • Histogram analysis can identify whether analysers are misclassifying giant platelets as small RBCs or microcytes as platelets.

• Mean Corpuscular Volume (MCV):
  • We use the Sysmex XN-V analyser. The Sysmex directly measures MCV using hydrodynamic focusing, forcing individual RBCs into a single file line which is passed through a laser beam. Increased MCV can indicate regeneration (reticulocytes are bigger than mature RBCs) or breed-specific macrocytosis (e.g., poodles). Decreased MCV may suggest iron deficiency, portosystemic shunts, or breed-specific traits (e.g., Akitas), and can also reflect in vitro cell shrinkage in hyponatraemic patients (think osmosis).

• Mean Corpuscular Haemoglobin (MCH) & Mean Corpuscular Haemoglobin Concentration (MCHC):
  • MCH is the amount of Hb per red blood cell [(Hb/RBC) x10], and so does not account for the volume of the cell.
  • MCHC is calculated as [(Hb/HCT) x 100], which accounts for the cell volume (since HCT is calculated using MCV). Both MCH and MCHC are susceptible to the interferences which affect Hb and RBC count (e.g., lipemia falsely elevates Hb).
• Red Cell Distribution Width (RDW):
  • Reflects anisocytosis. Elevated RDW often accompanies regenerative anaemia or recent blood transfusions, for example.
• Reticulocyte Count:
  • A critical marker of bone marrow activity. In mild anaemia, even a “normal” reticulocyte count might signal regeneration. Manual reticulocyte counts are often necessary for cats due to the persistence of punctate reticulocytes; aggregate reticulocytes provide a clearer indication of recent bone marrow activity.
• Nucleated RBCs (nRBCs):
  • Indicates accelerated turnover. Their presence in peripheral blood reflects the bone marrow’s attempt to meet increased demand, but it may also signify marrow disruption or extramedullary haematopoiesis.
• Retic-He:
  • A marker of iron availability. This is an early warning for iron restricted haematopoiesis and would be low in developing iron deficiency anaemia. However, it is relatively non-specific and is commonly low in patients with neoplasia, immune mediated disease and inflammation.

 

RBC histogram created by direct current sheath flow detection. Cells which are between 40 and 150fL are classified as RBCs. The small peak to the left of the x-axis represents platelets.

 

 

2. White Blood Cell Indices

• Total WBC Count and Differential:
  • Many laboratory analysers will use more than one method to generate accurate total WBC counts, but nRBCs can falsely elevate these if not excluded manually. A blood smear review remains vital, and manual differential count would be performed if there are unusual changes such as neutrophil toxicity or atypical cells.
• Neutrophil Count:
  • Neutrophilia suggests inflammation or stress (corticosteroid response). The presence of band neutrophils (left shift) signals increased inflammatory demand and can make it challenging for the analyser to accurately gate these populations.
• Monocyte Count:
  • Elevated counts often accompany chronic inflammation but can also reflect stress.
• Eosinophil Count:
  • Eosinophilia may point to parasitic, allergic, or paraneoplastic conditions.

 

WBC DIFF plot generated by the Sysmex XN-V. The plot on the left is from a healthy dog whilst the plot on the right is from a dog with marked toxic change and a left shift. The overlapping of the clouds indicates that the analyser is not able to confidently gate the different cell populations, and we should interpret the cell counts with caution.

 

 

3. Platelet Parameters

• Platelet Count:
  • Our analysers use two methods to count platelets: impedance (PLT-I) and optical (PLT-O). PLT-O uses fluorescent markers to identify platelets and tends to better mitigate the effects of platelet clumping, which can cause pseudothrombocytopenia. A blood smear review is essential to confirm platelet numbers and evaluate morphology.
  • Differentials for thrombocytopenia include consumption (usually mild reductions), immune-mediated destruction (marked reductions) and decreased production (e.g. bone marrow or infectious diseases).

• Platelet Volume (MPV):

• • Larger platelets suggest increased turnover, as seen in recovery from thrombocytopenia or bone marrow stimulation.

 

PLT histogram illustrates the impedance method. Cells which are between 10 and 40fL are classified as PLTs. The large peak to the right of the x-axis are RBCs.

 

Why Is the CBC Useful?

A CBC helps to answer critical questions like:

• Is the anaemia regenerative or non-regenerative?
  • Regenerative anaemia favours underlying haemorrhage or haemolysis (e.g. IMHA).
  • Non-regenerative anaemia often indicates chronic disease, iron deficiency, or bone marrow disorders (e.g., precursor-targeted immune-mediated anaemia [PIMA]).
• What’s driving the leukocyte changes?
  • Inflammatory leukograms feature a neutrophilia and monocytosis, often with toxic change and left shifts. Stress leukograms may have a concurrent lymphopenia, and toxic changes are not present. Eosinophilia prompts investigation for parasites, allergies, or neoplasms.
• What about platelets?
  • Mild thrombocytopenia could reflect consumption, whilst severe thrombocytopenia raises suspicion for immune-mediated thrombocytopenia (IMTP). Thrombocytosis might accompany inflammation or iron deficiency.
• Are multiple lineages affected?
  • Bicytopenia or pancytopenia signals potential bone marrow involvement. Neutropenia and thrombocytopenia typically precede anaemia due to the longer lifespan of RBCs. Bone marrow aspiration is helpful to identify whether the marrow is responding appropriately, and may reveal underlying causes, such as leukaemia, infection (e.g., Ehrlichia, Leishmania), or immune mediated destruction (e.g., PIMA).
  • Concurrent anaemia and thrombocytopenia can create a chicken or egg dilemma – which came first? This is why a detailed clinical history is vital.

Personal Reflections on the CBC

The CBC is a powerful diagnostic tool, but the analyser is not foolproof. Throughout my residency I have learned to identify and flag erroneous results caused by factors such as RBC agglutination, hyponatraemia or sample lipemia. Identifying these unusual results and working out the mechanisms behind the error has encouraged me to gain a deeper understanding of how haematology analysers work, as well as the importance of assessing dot plots and the meaning behind the lesser-known indices which are often overlooked. Each case builds a richer understanding of the nuances in haematology.

Final Thoughts

Interpreting a CBC is both an art and a science. Each value tells a story, and together, they reveal the body’s dynamic response to health and disease. By combining analyser results, blood smear reviews, and clinical context, we can uncover the deeper narratives within our patients and provide them with the best possible care.

Next time you receive a CBC report, take a moment to appreciate the wealth of information it offers. And remember, when in doubt, look at the smear — it might just surprise you.