Interactive Haematology

Question 1

Describe where you would see … myeloblasts
<5%
5-20%
>20%

Answer 1

<5%: Normal BM
5-20%: Myelodysplasia
>20%: Acute Myeloid Leukaemia (AML)

Question 2

Where should myeloblasts never be seen?

Answer 2

Peripheral blood
Presence indicates AML or leucoerythroblastic picture

Question 3

Which cells may contain Auer rods ?

Answer 3

Myeloblasts (though not all)

Question 4

Describe where you would see … lymphoblasts
<5%
>20%

Answer 4

<5%: Normal BM
>20%: Acute Lymphoblastic Leukaemia

Question 5

Give 2 causes of an MCV of 50-70

Answer 5

IDA
Thalassaemia

Question 6

Give 3 causes of an MCV of 100-108

Answer 6

Hypothyroidism
Alcoholism
Combined Iron + Folate deficiency

Question 7

Give 2 causes of an MCV of 115-125

Answer 7

B12 deficiency
Folate deficiency

Question 8

Name 2 B cell markers and what they are epitopes for

Answer 8

CD19: CAR T cells
CD20: Rituximab MOAB

Question 9

Name 4 T cell markers

Answer 9

CD3 (Mature)
CD4 (Helper)
CD8 (Cytotoxic)
CD5

Question 10

Name a marker of lymphoid differentiation

Answer 10

TdT: marker of immature T + B lymphoblasts

Question 11

Name a marker of mature B cells and plasma cells

Answer 11

Surface Immunoglobulini

Question 12

Give 2 causes of raised globulins

Answer 12

Monoclonal rise due to lymphoid malignancy: Myeloma
Polyclonal rise as part of reactive response: Infection, SLE, untreated HIV

Question 13

How does myeloma cause a rise in immunoglobulins?

Answer 13

Excess of clonal plasma cells
Plasma cells secrete immunoglobulins
Immune paresis: e.g. in IgG myeloma, massively raised IgG, so remaining IgA + IgM are suppressed

Question 14

What patterns of abnormalities should you look for when interpreting bloods?

Answer 14

Isolated single lineage cytopenia (all other values normal)
Pancytopenia
Isolated single lineage raised (all other values normal)
Isolated single lineage raised (other values suppressed)

Question 15

How should you look at blood values?

Answer 15

1. As a “group”:
   Hb + MCV
   WBC + differential
   Platelets
2. Pattern
3. Morphology

Question 16

Name 2 conditions in which spherocytes may be seen

Answer 16

AIHA
Hereditary spherocytosis

Question 17

What test determines whether spherocytosis is inherited or acquired?

Answer 17

DAT

Question 18

List 4 causes of hereditary haemolytic anaemia

Answer 18

Hereditary spherocytosis
G6PD deficiency
Sickle cell (structural Hb pathy)
Thaalassaemia major (globin chain imbalance)

Question 19

Name 2 types of acquired immune haemolytic anaemia

Answer 19

Autoimmune: linked to other immune disease
Alloimmune: post-blood transfusion

Question 20

Name 4 causes of acquired non-immune haemolytic anaemia

Answer 20

Malaria
Drugs
Oxidant drugs
Snake venom

Question 21

List 4 features of haemolytic anaemia regardless of aetiology

Answer 21

Unconjugated hyperbilirubinaemia
Reticulocytosis
Raised LDH
Lowered haptoglobins (bind to free Hb, thus are consumed)

Question 22

What distinguishes anaemia of chronic disease from iron deficiency?

Answer 22

L Fe: confirms Fe deficiency
N/ H Fe: can be ACD (or Fe deficiency with inflammation)
L/N Transferrin/ TIBC: ACD
H Transferrin/ TIBC: Fe deficiency

Question 23

What is ACD?

Answer 23

Anaemia of inflammation, mediated by high hepcidin levels
Body stores Fe adequate but sequestered + unavailable for erythropoeisis

Question 24

How are iron stores sequestered in ACD?

Answer 24

Hepcidin is master regulator of Fe
Elevated hepcidin inhibits GI absorption of Fe + sequesters Fe in macrophage + kupffer cells

Question 25

Why are iron stores sequestered in inflammation?

Answer 25

Hepcidin is an antibacterial/ inflammatory response protein Removing available Fe from blood circulation deprives invading bacteria of Fe required for rapid proliferation

Question 26

What can cause an isolated single lineage cytopenia with otherwise normal FBC?

Answer 26

Often peripheral destruction/ shortened survival Less often failure of production

Question 27

What can cause peripheral destruction/ shortened survival resulting in isolated cytopenia?

Answer 27

Immune destruction Non immune: Infections (malaria), mechanical (DIC), consumption sequestration (splenomegaly)

Question 28

What can cause failure of production resulting in isolated cytopenia?

Answer 28

Haematinics: Fe deficiency Drugs causing isolated agranulocytosis

Question 29

What kind of cytopenia is caused by B12/ folate deficiency?

Answer 29

Pancytopenia B12/ folate required for DNA synthesis Failure in all 3 lineages coming out of BM More marked in erythroid as more rapid turnover

Question 30

What cytopenia is generally seen with bone marrow disorders?

Answer 30

Pancytopenia Suppression of all lineages

Question 31

Give 2 non malignant causes of pancytopenia

Answer 31

DNA synthesis failure (B12/ folate deficiency) Aplastic anaemia (Chemo drugs, Idiosyncratic post hep C)

Question 32

Give 2 malignant causes of pancytopenia

Answer 32

Metastatic non-haematological cancer that has spread to the bone marrow Haematological cancer infiltrating BM: Acute leukaemia, myelodysplasia, myeloma, lymphoma

Question 33

Name 5 cancers that metastasise to the bone

Answer 33

Breast Prostate Lung Thyroid Kidney

Question 34

What distinguishes non malignant from malignant causes of pancytopenia?

Answer 34

Malignant has leucoerythroblastic picture

Question 35

What is the sigle most useful test to confirm the likely haematological diagnosis?

Answer 35

BCR ABL 1 RT-PCR assay for chronic myeloid leukaemia Blood film: excess white cells, heterogenous, mainly myeloid

Question 36

What is the likely cause of massive splenomegaly +/- hepatomegaly?

Answer 36

Chronic myeloid leukaemia

Question 37

What is the likely cause of hepatosplenomegaly and lymphadenopathy?

Answer 37

Lymhoid disorders

Question 38

How can CML be monitored during treatment?

Answer 38

RT-PCR for % of cells with BCR-ABL fusion protein to get ratio of malignant: normal

Question 39

What is the most useful haematological test? What is the diagnosis?

Answer 39

Immunophenotyping for CD19/CD5/CD3 CLL Blood film: mature normal lymphocytes, lots of smudges/ smear cells (rupture of fragile lymphocytes)

Question 40

Describe the normal expression of CD5 and CD19 in lymphocytes

Answer 40

T: CD5 +ve, CD19 -ve B: CD19 +ve, CD5 -ve

Question 41

What is the worst cell based prognostic factor in CLL?

Answer 41

Chr 17p deletion +/- TP53 point mutation

Question 42

What are the clinical issues of CLL?

Answer 42

Increased risk of infection: non functional mature B cells + hypogammaglobulinaemia BM failure: malignant cell proliferation Lymphadenopathy +/- splenomegaly: spread Transformation to high grade lymphoma AI complications e.g. AIHA

Question 43

Name 3 tyrosine kinase inhibitors

Answer 43

Imatinib: ABL TK inhibitor Ruxolotinib: JAK2 TK inhibitor Ibrutinib: Bruton TK inhibitor

Question 44

What tyrosine kinase inhibitor can be used in the targeted treatment of CLL?

Answer 44

Ibrutinib Deprive B cells of bruton TK to recreate phenotype of lacking B cells which is seen in Bruton's X-linked agammaglobulinaemia

Question 45

Give 3 treatment options in CLL

Answer 45

BCR kinase inhibitors e.g. Ibrutinib BCL2 inhibitors e.g. Venetoclax Chimaeric Antigen Receptor T cells (CAR-T)

Question 46

What is the most common cause of renal failure in multiple myeloma?

Answer 46

Cast nephropathy High serum free light chain levels Can pass through BM in kidneys + precipitate in tubules