Haematology 6 - Haematology in systemic disease and intro to haematopathology

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

Altitude

EPO-secreting tumour

Question 12

Recall 3 secondary causes of reduced erythrocytes

Answer 12

Bone marrow inflitration
Deficiency (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

Gastric
Renal
Bladder

Question 16

What are the morphological features of leuco-erythroblastic anaemia?

Answer 16

Immature bone marrow blood cells in peripheral blood

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 infection
Malignancy: myelofibrosis/ leukaemia/lymphoma/myeloma/metastatic non-haematological Ca
USUALLY A MALIGNANCY INVOLVING BONE MARROW

Question 18

What are the laboratory features of haemolytic anaemia?

Answer 18

Anaemia (though may be compensated)

Reticulocytosis

Unconjugated hyperbilirubinaemia

LDH raised

Reduced haptoglobins

Question 19

Which test detects immune haemolytic anaemia (an acquired cause)?

Answer 19

DAT/Coombs

DAT +’ve and presence of spherocytes -> immune haemolytic anaemia

Question 20

Recall 2 malignancies that can cause immune haemolytic anaemia?

Answer 20

Lymphoma

CLL

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. Malaria (no immune mechanism - just toxic breakdown by the parasite)
2. MAHA - microangiopathic haemolytic anaemia (reticulocytes will be raised)

Question 23

Recall 2 causes of MAHA

Answer 23

1. Underlying adenocarcinoma

2. 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 neutrophilia

Malignant hasimmature cells + either basophils and myelocytes (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

CLL

Non-Hodgkins lymphoma

Question 29

Name primary causes of haemolytic anaemia

Answer 29

Always a problem with the red cells themselves whereas secondary causes will be due to defects of the environment

Any of: 
Hereditary spherocytosis
G6PD deficiency
Sickle cell
Thalassaemia

Question 30

How can DIC cause MAHA?

Answer 30

Procoagulant factors released

In 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)

Useful to look at if unsure about glandular fever vs mature lymphocyte malignancy

Question 32

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

Answer 32

Flow cytometry (liquid tumour)
Immunohistology (solid tumour)
Use: working out if T or B lineage, working out if myeloid or lymphoid - by seeing if they express markers from that lineage

Question 33

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

Answer 33

Translocations
FISH studies (interphase FISH or metaphase FISH)
Use: looking for chromosomal markers e.g. 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

PCR
Pyro sequencing
Use: Detect JAK2 mutation, or BCR ABL cDNA

Question 35

What is the difference between primary and secondary disorders?

Answer 35

Primary = issue with bone marrow production - haematological.
These can be germ-line mutations or acquired/somatic mutations later in life.

Secondary = systemic issue which affects blood components but bone marrow production is fine