HAEM: Haemolytic anaemias and systemic disease

Question 1

What does the VHL gene mutation cause?

Answer 1

Chuvash polycythaemia - excess erythrocytes

Question 2

How do corticosteroids affect leukocytes?

Answer 2

Raised`

Question 3

4 types of anaemia?

Answer 3

Iron deficiency
AI haemolytic
Microangiopathic
Leukoerythroblastic

Question 4

2 cancers which cause occult blood loss.

Answer 4

GI

Urinary

Question 5

What does leukoerythroblastic mean? Give an example of their morphology.

Answer 5

RBC and WBC of variable degree of maturation

e.g. Tear drop aniso/poikilocytes (this is usually a sign of myelofibrosis), myelocytes, nucleated RBCs

Question 6

3 causes of leukoerythroblastic blood film?

Answer 6

Malignancy - haem or non-haem
Severe infection
Myelofibrosis (tear drop poikilocytes)

Question 7

What bilirubin is raised in haemolytic anaemia?

Answer 7

Unconjugated

Question 8

What are haptoglobin levels in HA?

Answer 8

Reduced

Question 9

What Ig in cold vs warm HA?

Answer 9

Warm = IgG -> extravascular 
Cold = IgM -> intravascular

Question 10

Which HA presents with Raynaud’s?

Answer 10

Cold

Question 11

Which HA occurs in CLL, SLE, methyldopa use?

Answer 11

Warm

Question 12

Which HA occurs in EBV and mycoplasma infections?

Answer 12

Cold

Question 13

Which HA in lymphoma?

Answer 13

Cold or warm

Question 14

Which tx for cold HA?

Answer 14

Supportive + chlorambucil chemo

Question 15

Which tx for warm HA?

Answer 15

Steroids, splenectomy, immunosuppress

Question 16

Which abs in PNH?

Answer 16

Donath-Landsteiner IgG ,anti-RBCs - on rewarming cause complement-mediated HA

Question 17

What is seen on blood film in immune HA?

Answer 17

Spherocytes and agglutination

Question 18

What does the DAT vs IAT look for?

Answer 18

DAT - looks at surface of RBCs for complement/Abs

IAT - looks at serum

Question 19

3 non-immune HA.

Answer 19

Malaria
MAHA
PNH (Ham’s test +ve)

Question 20

Which malignancy can cause MAHA?

Answer 20

Adenocarcinoma –> granules into circulation –> pro-coagulant –> low-grade DIC + RBC fragmentation

Question 21

What mutation causes TTP?

Answer 21

ADAMTS13 –> lack of vWF cleaving protease so it builds up to shred RBCs

Question 22

Over what % myeloblasts is abnormal in BM?

Answer 22

> 5%

Question 23

3 infections without neutrophilia?

Answer 23

Viral
Brucella
Typhoid

Question 24

What malignancy: neutrophilia + basophilia + myelocytes + splenomegaly = ?

Answer 24

CML

Question 25

What malignancy: neutropenia + myeloblasts = ?

Answer 25

AML

Question 26

What does the FIP1L1-PDGFRa fusion gene cause?

Answer 26

Chronic eosinophilic leukaemia

Question 27

Which viral infections cause monocytosis?

Answer 27

CMV | VZV

Question 28

Which bacterial infections cause monocytosis?

Answer 28

EBV CMV Toxoplasmosis

Question 29

What technique is used to determine clonality of B cells?

Answer 29

light chain restriction

Question 30

What is normal B cell clonality?

Answer 30

Polyclonal k:l 60:40 Abnormal would be monoclonal e.g. k:l 99:1

Question 31

Which technique used to decide if myeloid or lymphoid?

Answer 31

Immunophenotyping

Question 32

What are the main 3 types of haem mutations?

Answer 32

Type 1 - pro-proliferation Type 2 - anti-differentiation Anti-apoptosis - pro-survival

Question 33

Name an anti-apoptosis mutation.

Answer 33

BCL-2

Question 34

Name a pro-proliferation mutation.

Answer 34

BCR-ABL, JAK2

Question 35

Name an anti-differentiation mutation.

Answer 35

PML-PARA

Question 36

Which neoplasm is TdT +ve, CD19 +ve , surface Ig -ve?

Answer 36

B cell ALL

Question 37

What does TdT +ve mean?

Answer 37

Immature cells - B

Question 38

What does TdT -ve, Ig +ve and CD138 +ve indicate?

Answer 38

MM

Question 39

Intravascular causes of haemolysis

Answer 39

``` Malaria (MOST COMMON) G6PdD ABO Cold AIHA Drugs MAHA PNH ```

Question 40

What is the mutation in Gilbert's?

Answer 40

UGT1A1

Question 41

Which anaemia has alpha and beta spectrin and protein 4.1?

Answer 41

Elliptocytosis

Question 42

Which anaemia has band 3, protein 4.2, beta spectrin and ankyrin?

Answer 42

Spherocytosis

Question 43

What is the inheritance of spherocytosis and elliptocytosis?

Answer 43

AD for both

Question 44

What tests can be done in spherocytosis?

Answer 44

Osmotic fragility | Less Eosin-5-maleimide binding on flow cytometry

Question 45

What does the homozygous state for elliptocytosis cause?

Answer 45

Hereditary pyropoikilocytosis - fragmentation, budding, vesciculation of membrane and variation in size of RBCs

Question 46

What is the inheritance of G6PD?

Answer 46

X linked recessive

Question 47

Role of G6PD normally?

Answer 47

Generates NADPH to protect cell against oxidative stress

Question 48

What cell types are seen in G6PD?

Answer 48

Hemi ghosts (Hb on one side) Bite cells Nucleated RBC

Question 49

What is seen on G6PD slide when stained with methylviolet?

Answer 49

Heinz bodies = deformed haemoglobin peripherally

Question 50

Which pathway is defective in PK deficiency?

Answer 50

Glycolytic

Question 51

What cells are seen in PKD?

Answer 51

Echinocytes - short projections on RBCs | Spherocytes

Question 52

Which HA is basophilic stippling seen in?

Answer 52

Pyrimidine 5'-nucleotidase deficiency (uncommon) - nucleotide metabolism pathway defect

Question 53

When can splenectomy be done in HA?

Answer 53

>3yo but <10yo for maximal benefit before puberty