Labs

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Labs (1 of 40 slides)

Labs (2 of 40 slides)

Let’s begin with the patient’s CBC:

WBC (109/L)Hb (g/dL)MCV (fL)PLT (109/L)
1446.285210

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW-SD, red cell distribution width-standard deviation; platelets, PLT; Normal values: WBC 5-10 x 109/L, RBC 4-6 x 1012/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45%, platelets (PLT) 150-450 x 109/L

Labs (2 of 40 slides)

White cell differential – the percentages

White cell typePercentage (%)
Neutrophils35
Bands18
Lymphocytes4
Monocytes5
Eosinophils2
Basophils8
Metamyelocytes9
Myelocytes15
Promyelocytes1
Other3

White cell differential – let’s calculate the absolute values

White cell typePercentage (%)Absolute count (x 109/L)
Neutrophils3550
Bands1826
Lymphocytes45.76
Monocytes57.2
Eosinophils22.9
Basophils811.5
Metamyelocytes9 (we tend not discuss absolute counts)
Myelocytes15 (we tend not discuss absolute counts)
Promyelocytes1 (we tend not discuss absolute counts)
Other3 (we tend not discuss absolute counts)
To obtain absolute counts, multiply the total white cell count by the % of that white cell type

Therefore, the patient has neutrophilia, eosinophilia, basophilia, monocytosis and lymphocytosis!

If the patient had only 2% neutrophils, would they have neutropenia and be at increased risk for infection?

a
Yes
b
No
His absolute neutrophil count would be 144 x 10^9/L x 0.02 = 2.8 x 10^9/L, which is in the normal range. He would not be at increased risk for infection on the basis of his neutrophil count.

Can a patient with 99% neutrophils have neutropenia?

a
Yes
Sure, if the total white cell count is low (less than about 1.5 x 10^9/L)
b
No

The patient has significant eosinophilia. Does that mean we should consider common causes of eosinophilia such as allergy, parasites and drug effect?

a
Yes
b
No
There are enough other clues in the CBC and white cell count/differential that point to a completely different diagnosis.

What more can you say about the patient’s white cell count and differential based solely on the lab values?

a
Leukemoid reaction
Leukemoid reactions (typically > 50-100 × 10^9/L) occur in response to reactive causes of leukocytosis. We do not yet know whether this case represents a reactive or clonal increase white cells.
b
Hyperleukocytosis
Defined by WBC > 100 × 10^9/L
c
Leukostasis
Clinically defined as patient with leukemia and hyperleukocytosis who presents with respiratory, neurological, or renal compromise. We do not have enough information from the white cell count alone to make this diagnosis, though we are suspicious based on the history of blurry vision.
d
Leukoerythroblastosis
Defined by presence of immature neutrophil precursors (with or without leukocytosis) and nucleated red blood cells in peripheral blood, indicative of severe disruption of the marrow by overwhelming infection, myelofibrosis, or bone marrow invasion due to malignancy. We do not have any information about the presence of nucleated red cells.

What does the differential diagnosis include at this point?

a
Infection
Infection may cause a leukemoid reaction (white cell count > 50 x 10^9/L), though it would be unusual to cause counts this high and this degree of left shift. Nonetheless, we would want to rule it out.
b
Solid tumor (non-hematological cancer)
Patients with cancer may develop very high white cell counts. This is another type of leukemoid reaction, termed paraneoplastic.
c
Thalassemia
Patients with hemoglobinopathies do not develop hyperleukocytosis unless they have another underlying cause such as infection or leukemia.
d
Inflammation
Some non-infectious causes of inflammation may lead to significant leukocytosis including a leukemoid reaction, though they rarely cause white cell counts this high or this degree of left shift.
e
Hematological malignancy
Yes! I hope you will agree there is concern for a diagnosis of leukemia, specifically chronic myelogenous leukemia (CML).

What would you look for on the peripheral smear to support a diagnosis of leukemoid reaction?

a
Parasitic inclusions in red cells
Infections such as Babesiosis and Malaria generally do not cause hyperleukocytosis.
b
Dohle bodies
These are sky-blue inclusions, typically at the periphery of reactive (toxic) neutrophils. They consist of ribosomes and endoplasmic reticulum. They are seen in bacterial infections but also following tissue damage including burns, in inflammation, and following administration of G-CSF.
c
Toxic granulation
Toxic granulation is the term used to describe an increase in staining density and possibly number of granules that occurs regularly with bacterial infection and often with other causes of inflammation.
d
Auer rods
These are large, crystalline cytoplasmic inclusion bodies sometimes observed in myeloid blast cells during acute myeloid leukemia.
e
Hypersegmented neutrophils
These are observed in patients with megaloblastic anemia. They are defined as the presence of neutrophils with six or more lobes or the presence of more than 3% of neutrophils with at least five lobes.

Let’s consider the peripheral smear findings according to cause of hyper-leukocytosis

ConditionFindings
Solid tumorActivated neutrophils (toxic granulation, Dӧhle bodies, and cytoplasmic vacuoles); myelophthisic picture (nucleated red blood cells, granulocyte precursors, and teardrop-shaped erythrocytes) if bone marrow is infiltrated with tumor cells
InfectionActivated neutrophils (toxic granulation, Dӧhle bodies, and cytoplasmic vacuoles); decreased platelets, schistocytes 
G-CSFActivated neutrophils (toxic granulation, Dӧhle bodies, and cytoplasmic vacuoles)
CMLLeukoerythroblastic blood picture with increased bands and more immature myeloid cells

The patient’s smear appears as follows:

14.2: Chronic Myelogenous Leukemia (CML) - Medicine LibreTexts

The molecular test for CML takes some time to come back. In the meantime, we need to consider treatment (see next section).