Haemoglobinopathies

Question 1

What are the genetics of sickle cell?

Answer 1

Autosomal recessive

Question 2

When do symptoms from sickle cell appear?

Answer 2

4-6 months
HbSS takes over from HbF

Question 3

What is the long term management of sickle cell?

Answer 3

Hydroxycarbamide - raises HbF levels
Exchange transfusion
Supportive

Question 4

What are the types of sickle cell crisis?

Answer 4

Vaso-occlusive (painful)
Acute chest crisis
Aplastic
Sequestration

Question 5

What precipitates vase-occlusive crises?

Answer 5

Infection
Dehydration
Altitude
Hypoxis

Question 6

How are vast-occlusive crises diagnosed in sickle cell?

Answer 6

Clinical diagnosis

Question 7

What is the pathophysiology of a chest crisis in sickle cell?

Answer 7

Vaso-occlusion in pulmonary microvasculature –> infarction in lung

Question 8

What is seen on CXR in chest crisis?

Answer 8

Pulmonary infiltrates

Question 9

What is the management of chest crisis?

Answer 9

Supportive - pain relief, antibiotics, oxygen
Transfusion - improves oxygenation

Question 10

What is an aplastic crisis in sickle cell?

Answer 10

Sudden fall in haemoglobin due to parovirus suppressing bone marrow

Question 11

What is seen on bloods in aplastic crisis?

Answer 11

Low Hb
Reduced reticulocyte count

Question 12

What is a sequestration crisis in sickle cell?

Answer 12

Sickling within organs such as spleen or lungs causes pooling of blood with worsening of anaemia

Question 13

What is seen on bloods in sequestration crisis?

Answer 13

Raised retics

Question 14

What is alpha thalassaemia?

Answer 14

Deficiency of alpha chains in Hb

Question 15

What are the genetics of alpha thalassaemia?

Answer 15

Affects 2 alpha globulin genes on chromosome 16

Question 16

What determines the severity of alpha thalassaemia?

Answer 16

Number of alpha globulin alleles affected

Question 17

What is the picture be on bloods if thalassaemia affected 1-2 alleles?

Answer 17

Microcytic and hypochromic but Hb normal

Question 18

What s the picture on bloods if 3 alpha globulin alleles affected?

Answer 18

Hypochromic microcytic anaemia with splenomegaly

Question 19

What is beta thalassaemia trait?

Answer 19

Some but not all beta globulin alleles affected

Question 20

What is the characteristic picture on bloods of beta thalassaemia trait?

Answer 20

Mild hypochromic microcytic anaemia
Microsytosis normally disproportionate to anaemia

Question 21

What is beta thalassaemia major?

Answer 21

Absence of beta globulin chains

Question 22

What are the genetics of beta thalassaemia?

Answer 22

Autosomal recessive
Chromosome 11

Question 23

What is the presentation of meta thalassaemia major?

Answer 23

Failure to thrive
Hepatosplenomegaly
Microcytic anaemia
Normally presents in first year of life
Raised HbA2 and HbF

Question 24

What is the management of beta thalassaemia major?

Answer 24

Transfusion with iron chelation therapy

Question 25

What is the pathophysiology of G6PD deficiency?

Answer 25

Decreased G6PD --> decreased NADPH --> reduced glutathione --> increased red cell sensitivity to oxidative stress

Question 25

What is G6PD deficiency?

Answer 25

Glucose 6 phosphate deficiency Most common red blood cell enzyme defect

Question 26

What are the common features of G6PD deficiency?

Answer 26

Neonatal jaundice Intravascular haemolysis Gallstones

Question 27

What is seen on blood film with G6PD?

Answer 27

Heinz bodies Bite and blister cells

Question 28

What is the inheritance of G6PD?

Answer 28

X linked recessiveWhat

Question 29

population is G6PD normally seen in?

Answer 29

African or Mediterranean

Question 30

What is the typical history of G6PD?

Answer 30

Neonatal jaundice Gallstones Drugs precipitate haemolysis

Question 31

What drugs are associated with haemolysis in G6PD?

Answer 31

Anti-malarials - primaquine Cipro Sulphonamides, sulphasalazine, sulphonylureas

Question 32

How is G6PD diagnosed?

Answer 32

G6PD enzyme assay - 3 months post acute episode to allow time to recover

Question 33

What are the genetics of hereditary spherocytosis?

Answer 33

Autosomal dominant

Question 34

What population is hereditary spherocytosis seen in?

Answer 34

Northern Europeans

Question 35

What is the common presentation of hereditary spherocytosis?

Answer 35

Normally more chronic picture Failure to thrive Jaundice, gallstones, splenomegaly

Question 36

What precipitated haemolytic crisis in hereditary spherocytosis?

Answer 36

Parvovirus infection

Question 37

How is hereditary spherocytosis diagnosed?

Answer 37

Family history, typical clinical features and lab features - spherocytes, raised relics, raised MCHC

Question 38

What is used to diagnose hereditary spherocytosis if there is uncertainty?

Answer 38

EMA binding test

Question 39

What kind of haemolysis is seen in hereditary spherocytosis?

Answer 39

Extravascualr - so gets splenomegaly

Question 40

What kind of haemolysis is seen in G6PD?

Answer 40

Intravascular