Abnormal White Blood Cell Count

Question 1

What is the lymphoid lineage?

Answer 1

Lymphoid cells are lymphocytes = T cells, B cells and NK cells

Question 2

Which cells come under the myeloid lineage?

Answer 2

Erythrocytes  
Neutrophils 
Basophils  
Eosinophils 
Monocytes 
Macrophages  
Megakaryocytes  
Dendritic Cells

Question 3

Describe how the appearance of white cells changes as they develop.

Answer 3

They become smaller and their cytoplasm becomes clearer.

Question 4

Which factors stimulate the following cell lines:

a. Lymphoid
b. Myeloid
c. Erythroid

Answer 4

a. Lymphoid - IL-2
b. Myeloid - G-CSF, M-CSF
c. Erythroid - Erythropoietin

Question 5

Define Leukaemia.

Answer 5

A malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leukocytes.
This leads to suppression of the production of other blood cells such as erythrocytes, granulocytes and platelets.

Question 6

Define Lymphoma.

Answer 6

A group of blood cell tumours that develop from lymphatic cells.
If the disease is mainly in the lymphatic tissue then it is lymphoma.
If it is mainly in the blood it is leukaemia.

Question 7

Define Myeloma.

Answer 7

A malignant disease of the bone marrow characterised by two or moreof the following criteria:
 The presence of an excess of abnormal plasma cells in the bone marrow
 Typical lytic deposits in the bones on X-ray, giving the appearance of holes
 The presence in the serum of abnormal gammaglobulin, usually IgG

Question 8

Broadly speaking, what can cause an increase in white blood cell count?

Answer 8

Increased white blood cell production

Increased white blood cell survival

Question 9

What two broad categories of diseases can cause an increase in white production?

Answer 9

Reactive – in response to infection or inflammation

Primary – malignant

Question 10

What is the difference in the type of white blood cell seen in theperipheral blood of someone with an infection/inflammation (reactive) and someone with a malignancy (primary)?

Answer 10

Reactive – only mature white blood cells

Primary – mature AND immature white blood cells present

Question 11

Where does the mutation occur in chronic myeloid leukaemia?

Answer 11

GM-CFC phase (granulocyte-monocyte colony forming cell)

Question 12

If there are only immature cells in the blood film with low haemoglobin and low platelets, what would you suspect?

Answer 12

Acute leukaemia

Question 13

What are the normal ranges of:

a. Hb
b. Platelets
c. WCC
d. Neutrophils
e. Lymphocytes
f. Monocytes
g. Eosinophils
h. Basophils

Answer 13

a.Hb
120-160 g/L
b. Platelets 
150-400 x 109/L
c.WCC
4-11 x 109/L
d. Neutrophils 
2.5-7.5 x 109/L
e. Lymphocytes  
1.5-3.5 x 109/L
f. Monocytes 
0.2-0.8 x 109/L
g. Eosinophils 
0.04-0.44 x 109/L
h. Basophils 
0.01-0.1 x 109/L

Question 14

What can cause an elevated lymphocyte count?

Answer 14

Viral infections

Chronic lymphocytic leukaemia

Question 15

What is the lifespan of a neutrophil?

Answer 15

Hours in the peripheral blood

2-3 days in the tissues

Question 16

What is margination of neutrophils?

Answer 16

Around 50% of neutrophils in the circulation have marginated meaning that they have stuck to the wall of a damaged vessel (this means that they are NOT counted in the full blood count)

Question 17

Describe the differences in the appearance of neutrophils in infection compared to leukaemia.

Answer 17

Neutrophils in infection are granular (show toxic granulation)
Neutrophils in leukaemia do not have granules and do not look toxic.

Question 18

What else would be present in the blood film of someone with leukaemia that would not be present in someone with an infection?

Answer 18

Myelocytes and metamyelocytes – these precursors would not be found in the peripheral blood of someone responding to infection

Question 19

State some causes of neutrophilia.

Answer 19

Infection 
Inflammation  
Physical stress 
Adrenaline 
Corticosteroids  
Underlying neoplasia
Malignant neutrophilia (myeloproliferative disorders, chronic myeloid leukaemia)

Question 20

What types of infection cause neutrophilia?

Answer 20

Bacterial
Fungal
Certain viral infections Generally: if the neutrophil count is low but there are other features of infection, then you can deduce that it’s a viral infection

Question 21

State some infections that characteristically do NOT produce neutrophilia.

Answer 21

Brucella
Typhoid
Many viral infections

Question 22

State some reactive causes of eosinophilia.

Answer 22

Parasitic infection
Allergic diseases e.g. asthma
Neoplasms e.g. Hodgkin’s and Non-Hodgkin’s
Hypereosinophilic syndrome

Question 23

State a malignant cause of eosinophilia.

Answer 23

Malignant chronic eosinophilic leukaemia (INCREDIBLY RARE)

Question 24

What would you see in the chest X-ray of someone with Hodgkin’s lymphoma?

Answer 24

Increased mediastinal mass

Question 25

What can cause monocytosis?

Answer 25

RARE but it is seen in certain chronic infections and primary haematological disorders
TB, brucella, typhoid
CMV, varicella zoster
Sarcoidosis
Chronic myelomonocytic leukaemia (MDS – myelodysplastic syndrome)

Question 26

Describe the appearance of chronic lymphocytic leukaemia on a blood film.

Answer 26

The lymphocytes have a typical appearance – big nucleus + little cytoplasm
They are mature lymphocytes
This appearance can also be present in autoimmune and inflammatory conditions

Question 27

Describe the appearance of acute lymphoblastic leukaemia on a blood film.

Answer 27

There are immature lymphoblasts
They are much larger than the mature lymphocytes
Within the large nucleus you can see the nucleolus (showing that the cell is immature)

Question 28

Describe the difference in the expansion of lymphocytes in secondary (reactive) lymphocytosis compared to primary lymphocytosis.

Answer 28

Secondary lymphocytosis = polyclonal expansion

Primary lymphocytosis = monoclonal expansion

Question 29

State some causes of reactive lymphocytosis.

Answer 29

Infection (e.g. EBV, toxoplasma, infectious hepatitis, rubella, herpes infections)
Autoimmune disorders
Neoplasia
Sarcoidosis

Question 30

What do you see in the blood film of someone with mononucleosis syndrome?

Answer 30

Atypical lymphocytes
They look similar to immature lymphocytes but they aren’t very round an its cytoplasm extends between surrounding cells
The nucleus of the cell lacks nucleoli
This is typical of glandular fever
So if there is a high WCC and you find these reactive-looking lymphocytes you can suspect that it is a reactive, infection-induced lymphocytosis

Question 31

What is glandular fever caused by?

Answer 31

Epstein-Barr virus infection of the B-lymphocytes via the CD21 receptor
Infected B-cells proliferate and express EBV associated antigen
There is a cytotoxic T-lymphocyte response
Acute infection is resolved leading to life-long sub-clinical infection

Question 32

What is the usual cause of lymphocytosis in elderly people?

Answer 32

Chronic lymphocytic leukaemia (CLL)

Question 33

Explain how light chain restriction can be used to distinguish between causes of lymphocytosis.

Answer 33

In reactive lymphocytosis, there will be polyclonal expansion of the lymphocytes meaning that the light chains of the antigens produced by B cells and the B cell receptors will have a 50:50 kappa and lambda divide
In primary lymphocytosis, there will be a monoclonal expansion so you will get kappa or lambda restriction meaning that all the light chains are of one type

Question 34

Normally, B and T cells will undergo gene rearrangement in the TCR and Ig genes in a process called affinity maturation. How is this different in primary monoclonal proliferation of B and T cells?

Answer 34

With primary monoclonal proliferation, all the daughter cells carry identical copies of Ig genes or TCR genes