Thalassaemia

Question 1

Major form of adult haemoglobin

Answer 1

Alpha-2, beta-2 (HbA)

Question 2

Main groups of haemoglobinopathies (2)

Answer 2

Thalassaemias- decreased rate of globin chain production

Structural haemoglobin variants- normal production of abnormal globin chains e.g. HbS

Question 3

What pattern of anaemia do thalassaemias give rise to?

Answer 3

Microcytic hypochromic

Question 4

How many copies of alpha globin genes does a normal person have?

Answer 4

Four copies (two genes)

Question 5

Alpha-thalassaemias usually result from which kind of mutation?

Answer 5

Deletions of alpha genes

Question 6

How many copies of the alpha gene need to be deleted for symptoms? What is this condition called?

Answer 6

Three. HbH disease

Question 7

Features of HbH disease (3)

Answer 7

Microcytic anaemia
Splenomegaly
Jaundice due to haemolysis

Question 8

What causes Barts hydrops fetalis?

Answer 8

Lack of any functional alpha genes (–/–)

Question 9

Inheritance of HbH disease

Answer 9

Autosomal recessive

Question 10

Management of HbH disease

Answer 10

Transfusion (mild- during illness, severe- transfusion dependent)
Folic acid supplementation

Question 11

Diagnosis of alpha thalassaemia (4)

Answer 11

Suspected from red cell indices
Blood film
High performance liquid chromatography
Haemoglobin electrophoresis
PCR genotyping

Question 12

Features of blood film in alpha thalassaemia (4)

Answer 12

Microcytosis
Hypochromia
Anisocytosis (abnormal variation in red cell size)
Poikilocytosis (presence of abnormally shaped RBCs)

Question 13

Why is only HbA affected in beta thalassaemia?

Answer 13

Only Hb which has beta chains

Question 14

What is beta thalassaemia caused by?

Answer 14

Autosomal recessive point mutations which either inactivate (B^0) or reduce function (B^+) of beta-globin

Question 15

Classification of beta thalassaemia (3)

Answer 15

Trait- asymptomatic
Intermedia- requires occasional transfusion
Major- lifelong transfusion dependency

Question 16

Diagnostic features of beta thalassaemia major (3)

Answer 16

Elevated HbA2
Film: microcytic, target cells, anisopoikilocytosis
HPLC- mainly HbF

Question 17

Clnical features of beta thalassaemia major (4)

Answer 17

Aged 6-24 months
Failure to thrive
Pallor
Signs of extramedullary haematopoiesis

Question 18

Signs of extramedullary haematopoiesis in beta thalassaemia major (3)

Answer 18

Hepatosplenomegaly
Bony deformities
Organ damage

Question 19

Management of B-thal major

Answer 19

Regular transfusion programme to maintain Hb above 95-105g/l

Question 20

Main cause of morbidity/mortality from treated B-thal major

Answer 20

Iron overload

Question 21

Manifestations of iron overload

Answer 21

Cardiac- CCF,arrythmias
Liver cirrhosis, HCC
Endocrine dysfunction

Question 22

Other complications of B-thal major

Answer 22

Tranfusion-related
Hypersplenism
Increased sepsis risk due to leucopenia

Question 23

Management of iron overload in B-thal major

Answer 23

Iron chelating drugs such as desferrioxamine

Question 24

Why is compliance poor with desferrioxamine?

Answer 24

Parenteral administration

Question 25

Pathophysiology of sickle cell anaemia

Answer 25

Autosomal recessive specific point mutation in codon 6 of beta globin gene, creating Hb which polymerises at low [o2], distorting red cell membrane

Question 26

Manifestations of sickle cell trait (2)

Answer 26

Usually asymptomatic | Spontaneous haematuria may occur due to microvascular renal infarction

Question 27

Consequences of sickle cell anaemia

Answer 27

Tissue infarction due to vascular occlusion Chronic haemolysis Sequestration of RBCs in spleen/liver

Question 28

Long-term treatment of sickle cell anaemia

Answer 28

``` Prophylactic penicillin Vacccination Folic acid Top-up and exchange transfusions Hydroxycarbamide ```

Question 29

What does hydrocarbamide do?

Answer 29

Induces HbF production