Haemoglobinopathy

Question 1

What are the major forms of haemoglobin?

Answer 1

HbA
HbA2
HbF

Question 2

HbA2 contains what globin chains?

Answer 2

2 x alpha

2 x delta

Question 3

Control of alpha globin chain production occurs on which chromosome?

Answer 3

16

Question 4

How many alpha genes are present per chromosome?

Answer 4

2

Question 5

Control of beta globin chain production occurs on which chromosome?

Answer 5

11

Question 6

How many beta genes are present per chromosome?

Answer 6

1

Question 7

At what age does one reach adult levels of haemoglobin?

Answer 7

6-12 months

Question 8

What are the two main groups of haemoglobinopathies?

Answer 8

Thalassaemia

Structural haemoglobin variants

Question 9

What occurs in thalassaemia?

Answer 9

There is decreased rate of globin chain synthesis

Question 10

Inadequate haemoglobin production due to thalassaemia will cause what type of anaemia?

Answer 10

Microcytic (hypochromic)

Question 11

The accumulation of globin chains can be toxic to what?

Answer 11

Bone marrow - causes ineffective erythropoeisis

Question 12

How many alpha genes have been deleted in an alpha + thalassaemia?

Answer 12

One

Question 13

How many alpha genes have been deleted in an alpha 0 thalassaemia?

Answer 13

Both

Question 14

How many genes are missing if a patient has an alpha thal trait?

Answer 14

One or two (alpha + / alpha; alpha 0 / alpha; alpha + / alpha +)

Question 15

Having only one alpha gene present results in what condition?

Answer 15

HbH disease

Question 16

What occurs in Hb Bart’s hydrops fetalis?

Answer 16

When there are no functional alpha genes present

Question 17

Do patients with the alpha thal trait need treated?

Answer 17

No - asymptomatic

Question 18

What are haemoglobin, MCV and MCH levels like in HbH disease?

Answer 18

Low - very low MCV and MCH

Question 19

What happens to the excess beta chains in HbH disease?

Answer 19

They form HbH tetramers which cannot carry oxygen

Question 20

Give some clinical features of HbH disease

Answer 20

Moderate anaemia
Splenomegaly
Jaundice

Question 21

Where is HbH disease particularly common?

Answer 21

SE Asia
Middle East
Mediterranean

Question 22

Why is it so significant to have no alpha genes present?

Answer 22

As neither HbA or HbF can be made

Question 23

Give some clinical features of Hb Bart’s hydrops fetalis

Answer 23

Severe anaemia
Cardiac failure
Hepatosplenomegaly
Skeletal/CV abnormalities

Question 24

Is Hb Bart’s hydrops fetalis compatible with life?

Answer 24

No

Question 25

What type of mutations will cause beta thalassaemia?

Answer 25

Point

Question 26

What are the classifications of beta thalassaemia?

Answer 26

Beta thalassaemia trait Beta thalassaemia intermedia Beta thalassaemia major

Question 27

Are patients with the beta thalassaemia trait symptomatic?

Answer 27

No

Question 28

What is the diagnostic feature of beta thalassaemia trait?

Answer 28

Raised HbA2

Question 29

When does beta thalassaemia major present? Why?

Answer 29

6-24 months - level of HbF falls

Question 30

Give some clinical features of beta thalassaemia major

Answer 30

Pallor Failure to thrive Hepatosplenomegaly Bone deformities

Question 31

How is beta thalassaemia major managed?

Answer 31

Regular transfusion

Question 32

What is the main danger of regular transfusion in beta thalassaemia patients?

Answer 32

Iron overload - main cause of death

Question 33

Give some effects of iron overload in transfused patients

Answer 33

``` Endocrine dysfunction (diabetes/osteoporosis) Cardiac disease (cardiomyopathy) Liver disease (cirrhosis) ```

Question 34

What is used to manage iron overload?

Answer 34

Iron chelating drugs (desferrioxamine)

Question 35

How do iron chelators work?

Answer 35

They bind to the iron and form complexes which are excreted in urine/stool

Question 36

What genetic change occurs in sickling disorders?

Answer 36

A point mutation in the beta globin gene substituting glutamine to valine

Question 37

What effect does the point mutation have on haemoglobin?

Answer 37

It alters the structure of Hb to HbS

Question 38

What happens if HbS is exposed to low oxygen levels for a prolonged period?

Answer 38

It polymerises and damages the RBC membrane

Question 39

Are people with sickle trait symptomatic?

Answer 39

No - unless exposed to severe hypoxia (high altitude etc.)

Question 40

Patients with sickle cell anaemia have two faulty beta chains. True/false?

Answer 40

True - HbSS

Question 41

What occurs in a sickle cell crisis?

Answer 41

There are episodes of tissue infarction due to vascular occlusion

Question 42

Give some features of sickle cell anaemia

Answer 42

Chronic haemolysis Hyposplenism Pain (sickle crisis)

Question 43

Give some causes of sickle crisis

Answer 43

``` Hypoxia Dehydration Infection Cold exposure Stress ```

Question 44

How is sickle crisis treated?

Answer 44

``` Opiate analgesia Hydration Rest Oxygen Red cell exchange transfusion (severe crises) ```

Question 45

What is involved in the long-term management of sickle cell anaemia?

Answer 45

Prophylactic penicillin/vaccination (hyposplenism) Folate supplementation Hydroxycarbamide Transfusion

Question 46

How does hydroxycarbamide work?

Answer 46

It induces HbF production

Question 47

What technique is used to diagnose haemoglobinopathy?

Answer 47

HPLC

Question 48

What can HPLC identify?

Answer 48

``` Abnormal haemoglobin (Hbs) Raised HbA2 (beta thal trait) ```