Tales from haem clinic: WBC

Question 1

What is vacuolation?

Answer 1

When granulocytes have vacuoles

Question 2

When is vacuolation normally seen?

Answer 2

In infection

Question 3

What markers can show infection?

Answer 3

Inflammatory markers e.g., CRP
Sputum culture
Urine antigen test

Question 4

What is CRP?

Answer 4

c-reactive protein is released (from the liver) more if there is inflammation

Question 5

What are the types of leukocytes?

Answer 5

Question 6

What are symptoms/ features of viral infections/ glandular fever?

Answer 6

Tonsillar inflammation
Widespread palpable small lymph nodes (cervical, axillary, Inguinal)
Lymphocytosis
leukocytosis

Question 7

What are the areas of palpable lymph nodes?

Answer 7

cervical= neck
axillary= armpit
Inguinal= groin

Question 8

How would you confirm a diagnosis of infectious mononucleosis (mono)?

Answer 8

Testing for mononuclear heterophile antibodies
‘monospot’ test
or by looking. for igM antibodies to Epstein-Barr virus (EBV)

Question 9

What is a common type of lymphocyte when there is a viral infection?

Answer 9

atypical lymphocytes
- e.g., intensely basophilic cytoplasm

Question 10

What is a characteristic of infectious mononucleosis (glandular fever)?

Answer 10

scalloped margins and ‘hugging’ of the surrounding RBCs

Question 11

What are “smear/ smudge/ basket’ cells?

Answer 11

squashed mature lymphocytes

Question 12

What are smear/ smudge/ basket cells a characteristic of?

Answer 12

CLL

Question 13

How would you describe chronic lymphocytic leukaemia?

Answer 13

Lymphoproliferative disorder
it is the most common cause of persistent lymphocytosis in the elderly

Question 14

How can you confirm a diagnosis of CLL?

Answer 14

characterise the profile of cell surface markers expressed by lymphocytes using flow cytometry

Question 15

How is CLL staged?

Answer 15

according to the degree of lymph node/ liver/ spleen involvement
and whether Hb and platelet count are reduced (in more advanced disease)

Question 16

What are the clinical signs shown on the drawing.
(shows widespread bruising)

Answer 16

lymphadenopathy (enlarged lymph nodes)
enlarged liver (hepatomegaly)
enlarged spleen (splenomegaly)
testicular swelling

Question 17

Where is the lymphadenopathy in the image?

Answer 17

neck/ cervical
axillae
groin

Question 18

How do you recognise blast cells?

Answer 18

large size, high nucleus/ cytoplasm ratio, open chromatin patterns of nucleus, prominent nucleoli

Question 19

What is thrombocytopenia?

Answer 19

Low platelet count

Question 20

What is pancytopenia?

Answer 20

describes reduction in all 3 cell lineages

Question 21

What symptoms does leukocytosis with lymphoblasts circulating in the blood lead to?

Answer 21

lymphadenopathy
hepatomegaly
splenomegaly
testicular swelling

Question 22

What symptoms does anaemia (normocytic/ normochromic) lead to?

Answer 22

pale, lethargic/ listless (lack energy)

Question 23

What does symptoms does neutropenia lead to?

Answer 23

fever

Question 24

What symptoms does thrombocytopenia lead to?

Answer 24

bruising/ bleeding

Question 25

What are the symptoms/ characteristics of acute lymphoblastic leukaemia (ALL)?

Answer 25

listlessness, widespread bruising, febrile, pale, hepatomegaly, splenomegaly, testicular swelling, lymphadenopathy, low Hb (anaemia)

Question 26

What tests can you perform to get more information for the diagnosis of ALL?

Answer 26

Flow cytometry Cytometric/ molecular analysis bone marrow test (aspirate)

Question 27

What would bone marrow aspirate of ALL show?

Answer 27

shows replacement of normal bone marrow cells by lymphoblasts

Question 28

How can the lymphoblasts be further characterised?

Answer 28

by assessing the profile of their cell surface e.g., using flow cytometry

Question 29

How is cytogenetic and molecular genetic analysis useful with leukaemia?

Answer 29

- Cytogenetic/molecular genetic analysis is useful for managing the individual patient because it gives us information about prognosis - Cytogenetic/molecular genetic analysis advances knowledge of leukaemia because it has permitted the discovery of leukemogenic mechanisms and the development of targeted treatment

Question 30

What are approaches to treatment for ALL?

Answer 30

supportive - red cells - platelets - antibiotics systemic chemotherapy intrathecal (around the spinal cord) chemotherapy

Question 31

Why is both intrathecal and intravenous systemic chemotherapy required for ALL?

Answer 31

lymphoblasts infiltrate into the CNS, where they are protected from the systemic chemotherapy (aka sanctuary site)

Question 32

Describe the abnormalities on this blood film.

Answer 32

increased granulocytes, neutrophils, and basophils and an increase in granulocyte precursors (myelocytes and metamyelocytes)

Question 33

When you have extremely raised WBCs, what could be the cause of a patient's abdominal pain?

Answer 33

enlargement of spleen and possibly liver/ splenomegaly and hepatomegaly

Question 34

What does the ABL1 gene encode for?

Answer 34

tyrosine kinase enzyme (tightly regulated activity)

Question 35

What gives rise to a leukaemic clone?

Answer 35

BCR:ABL1 gene encodes a protein with uncontrolled tyrosine kinase activity, which gives rise to leukaemic clone

Question 36

What can be done to treat chronic myeloid leukaemia?

Answer 36

the BCR-ABL1 protein signals between the cell surface and the nucleus can be inhibited It can be inhibited by specific tyrosine kinase inhibitors leading to remission, and potentially cure of the disease

Question 37

What is the difference in blast cells from ALL and AML?

Answer 37

In AML, cytoplasm of blast cells contains granules, consistent with myeloblasts - flow cytometry will characterise these further

Question 38

What are characteristics of AML?

Answer 38

blast cells with granular cytoplasm (myeloblasts) anaemia with circulating nucleated RBCs Neutropenia Thrombocytopenia (low platelet count)

Question 39

Are you happy with this summary of the cases from this session.

Answer 39

Question 40

What are the clinical features that may be found in leukaemia?

Answer 40

Si or No (you want me to say it in spanish, no)

Question 41

What is the difference between acute and chronic leukaemias?- acute

Answer 41

- In Acute Leukaemia (AML or ALL) there is an increase in very immature cells (myeloblasts or lymphoblasts) with a failure of these to develop into mature leukocytes - In Acute leukaemia, the bone marrow is infiltrated by immature blast cells, resulting in impaired haemopoiesis: blast cells also circulate in the peripheral blood and can be seen on the blood film - If Acute leukaemias are not treated, the disease is very aggressive and patients die quickly

Question 42

What are the differences between acute and chronic leukaemia?- chronic

Answer 42

- In Chronic Leukaemias the leukaemic cells are mature, although abnormal: granulocytes or lymphocytes - In Chronic Leukaemias the disease and deterioration go on for a long period of time - In CML, the mature end cells are still able to function; in CLL the lymphocytes are functionally useless and there is a loss of normal immune function