B Lecture 2: Haematological Changes in Systemic Disease & Introduction to Leukaemia and Lymphoma Diagnosis

Question 1

What disease is characterised by primary raised erythrocytes?

Answer 1

Polycythaemia vera

Question 2

What disease is characterised by a secondary reduction in erythrocytes?

Answer 2

Auto-immune haemolytic anaemia

Question 3

Which disease is caused by a genetic deficiency of factor IX?

Answer 3

Haemophilia B

Question 4

Which disease is caused by a genetic excess of factor IX?

Answer 4

Factor IX Padua

Question 5

Which disease is caused by a genetic deficiency of erythrocytes?

Answer 5

Sickle cell disease/ HbS (beta globin gene mutation)

Question 6

How can haemophilia B be treated using gene therapy?

Answer 6

Factor IX Padua gene can be put into adenoviruses as a vector, to cause factor IX production

Question 7

Which disease is caused by an acquired mutation in JAK2?

Answer 7

Polycythaemia vera

Question 8

Which disease is caused by an acquired mutation in PIG A?

Answer 8

PNH paroxysmal nocturnal haemoglobinuria

Question 9

What is a raised factor VIII likely to be secondary to?

Answer 9

An inflammatory process

Question 10

How can haemophilia be acquired? (Rather than genetic)

Answer 10

Auto-immune disorder common in elderly - body produces autoantibodies directed against factor VIII

Question 11

Recall 2 secondary causes of raised erythrocytes?

Answer 11

AltitudeEPO-secreting tumour

Question 12

Recall 3 secondary causes of reduced erythrocytes

Answer 12

Bone marrow inflitrationDeficiency (B12/Fe) Haemolytic anaemia

Question 13

What is the most likely cause of iron deficiency anaemia?

Answer 13

Bleeding (until proven otherwise!)

Question 14

How is iron deficiency anaemia diagnosed?

Answer 14

Ferritin and transferrin saturation: both would be low

Question 15

Recall 3 types of cancer that may present first with an iron deficiency anaemia?

Answer 15

GastricRenalBladder

Question 16

What are the morphological features of leuco-erythroblastic anaemia?

Answer 16

Erythroblasts (nucleated red blood cells and tear drop red blood cells) Immature myeloid cells

Question 17

What are the causes of leucoerythroblastic anaemia?

Answer 17

Infection: miliary TB/severe fungal infectionMalignancy: myelofibrosis/ leukaemia/lymphoma/myeloma/ metastatic CaUSUALLY A MALIGNANCY INVOLVING BM

Question 18

What are the laboratory features of haemolytic anaemia?

Answer 18

Anaemia (though may be compensated)ReticulocytosisUnconjugated hyperbilirubinaemiaLDH raised Reduced haptoglobins

Question 19

Which test detects immune haemolytic anaemia?

Answer 19

DAT/Coombs

Question 20

Recall 2 malignancies that can cause immune haemolytic anaemia?

Answer 20

LymphomaCLL

Question 21

What type of anaemia is caused by mycoplasma infection?

Answer 21

Immune haemolytic anaemia

Question 22

What are the 2 main causes of non-immune/ Dat neg haemolytic anaemia?

Answer 22

1. Malaria2. MAHA - microangiopathic haemolytic anaemia

Question 23

Recall 2 causes of MAHA

Answer 23

1. Underlying adenocarcinoma2. Haemolytic uraemic syndrome

Question 24

How can CLL and AML be distinguished on blood film?

Answer 24

CLL has mature cells, AML has immature cells

Question 25

What is the main cause of neutrophilia?

Answer 25

Pyogenic infection

Question 26

How do you distinguish a reactive neutrophilia vs a malignant one?

Answer 26

Reactive neutrophilia has a limit (they won't be sky high) No immature cells in reactive neutrophiliaMalignant has immature cells + either basophils (indicative of CML) or myeloblasts (indicative of AML)

Question 27

What is the most common cause of a reactive lymphopaenia?

Answer 27

HIV

Question 28

In which 2 conditions might smear cells appear on the blood film?

Answer 28

CLLNon-Hodgkins lymphoma

Question 29

Name 2 primary causes of haemolytic anaemia

Answer 29

Any of: Hereditary spherocytosisG6PD deficiencySickle cellThalassaemia

Question 30

How can DIC cause MAHA?

Answer 30

Procoagulant factors releasedIn places where blood moves slowly (eg small vasculature) there is platelet deposition and fibrinogen is converted to fibrin Red cells pushed through fibrin web and fragmented

Question 31

How is B cell clonality determined?

Answer 31

Look for light chain restriction - the ratio of kappa and lambda (60:40 would be reactive, 99:1 would be malignant)

Question 32

Recall 2 tests that can determine immunophenotype in blood malignancies, and one use of knowing this info?

Answer 32

Flow cytometryImmunohistologyUse: working out if T or B lineage, working out if myeloid or lymphoid

Question 33

Recall 2 tests that can determine cytogenetics in blood malignancies and one use of knowing this info?

Answer 33

TranslocationsFISH studies Use: Philadelphia chromosome identification

Question 34

Recall 2 tests that can determine molecular genetics in blood malignancies and one use of knowing this info?

Answer 34

PCRPyro sequencingUse: Detect JAK2 mutation, or BCR ABL cDNA