Path Haem 2

Question 1

What proteins are most commonly mutated in hereditary spherocytosis?

Answer 1

Spectrin

or ankyrin

(they are RBC membrane proteins)

Question 2

What is the inheritance pattern of hereditary spherocytosis?

Answer 2

Autosomal dominant (75% cases)

however 25% of cases are recessive or de novo

Question 3

severity of hereditary spherocytosis

Answer 3

there is a range

mild (20-30%, often asymptomatic)
moderate (most common, usually presents in infancy or childhood)
severe (can even present in utero with hydrops fetalis)

Question 4

What is the classic triad that hereditary spehrocytosis presents with?

Answer 4

anaemia
splenomegaly
jaundice (due to increased unconjugated bilirubin)

Question 5

What additional risks are patients with hereditary spherocytosis at risk of?

Answer 5

• gallstone formation
• susceptibility to the effect of parvovirus B19 infection
• haemolytic / aplastic crises
• megaloblastic anaemia

Question 6

What is the underlying pathophysiology in hereditary spherocytosis?

Answer 6

1. Genetic mutation

→ defects in RBC membrane protein → sphere-shaped RBCs with decreased membrane stability
→ inability to change form while going through narrowed vessels

• Entrapment within splenic vasculature → splenomegaly
• Destruction via splenic macrophages → extravascular hemolysis

Question 7

What type of gallstones do people with hereditary spehrocytosis get?

Answer 7

black pigment gallstones

(can lead to cholecystitis)

Question 8

What findings can you see on blood smear in hereditary spherocytosis?

Answer 8

spherocytosis

potentially anisocytosis

Question 9

How do you diagnose hereditary spherocytosis?

Answer 9

• spherocytes
• flow cytometry (EMA binding test)
• positive osmotic fragility test (increased osmotic fragility (lysis in hypotonic solutions))
• DAT -ve (Coombs) -> not immune mediated

Question 10

Management of hereditary spherocytosis?

Answer 10

folic acid
splenectomy (sole definitive treatment)

phototherapy in neonates to prevent kericterus
blood transfusions may be required

Question 11

What vaccines should you give before splenectomy?

Answer 11

strep pneumoniae
HiB
N. meningitidis

Question 12

What are the functions of the spleen?

Answer 12

elimination of damaged erythrocytes from the blood stream

opsonisation and removal of encapsulated organisms from the bloodstream

Question 13

What is asplenia?

Answer 13

absence of normal spleen function (functional asplenia) or of the spleen itself (anatomic asplenia)

you can also have congenital asplenia, but this is very rare (1 in 10 000)

Question 14

typical blood smear + FBC findings in patients with asplenia

Answer 14

Howell-Jolly bodies
neutrophilia
thrombocytosis

Question 15

Important considerations in the management of asplenia in patients

Answer 15

MedicAlert bracelet
prevent dog/tick bites
caution when travelling to malaria endemic areas
immunise against encapsulated organisms
treat with antibiotics early

Question 16

What are the myeloproliferative disorders?

Answer 16

CML
ET (essential thrombocythaemia)
PV (polycythaemia vera)
PMF (primary myelofibrosis)

Question 17

What can be seen on BM in myelofibrosis?

Answer 17

fibrosis
‘‘dry tap’’

Question 18

What mutations are common in myelofibrosis?

Answer 18

JAK2 (60%) - Janus kinase
MPL mutation

CALR mutation

Question 19

What is Budd-Chiari syndrome?

Answer 19

a rare condition resulting from hepatic vein obstruction that leads to hepatomegaly, ascites, and abdominal discomfort.

• It is most commonly due to a thrombotic occlusion secondary to a chronic myeloproliferative neoplasm (e.g., polycythemia vera), but may be caused by other conditions associated with hypercoagulable states.

Question 20

What is the commonest and second most common inherited cause of exocrine pancreatic insufficiency in children?

Answer 20

1. CF
2. Schwachmann Diamond Syndrome

Question 21

What is the classical inheritance pattern of G6PD deficiency?

Answer 21

X-linked recessive

Question 22

What first line small molecule inhibitor is used in the treatment of chronic lymphocytic leukaemia?

Answer 22

Ibrutinib (tyrosine kinase inhibits)

Question 23

What does CML do to the spleen and how?

Answer 23

Classically it causes massive splenomegaly due to splenic infiltration of myeloid cells.

Question 24

What haematological changes are seen in pregnancy?

Answer 24

++ increased plasma volume
+ increased cell mass
- decreased Hb
+ increased MCV
decreased haemltocrit
decreased platelets
+ increased WCC
+ increased factors VII, VIIII, IX, X, XII
decreased Factor XI
decreased Protein S

Question 25

route of administration of Anti-D in pregnancy

Answer 25

IM but can also be given IV

Question 26

When is routine antenatal prophylaxis of anti-D given?

Answer 26

28 and 34 weeks

Question 27

What dose of anit-D is given during the routine antenatal timings and when are these?

Answer 27

250 IU given IM at 28 and 34 weeks