Haemoglobinopathy

Question 1

HbA?

Answer 1

2 alpha

2 beta

Question 2

HbA2?

Answer 2

2 alpha

2 delta

Question 3

HbF?

Answer 3

2 alpha

2 gamma

Question 4

What chromosome are alpha genes on?

Answer 4

16

2 genes per chromosome

Question 5

What chromosome are beta genes on?

Answer 5

11

One gene per chromosome

Question 6

What is the pattern of inheritance for haemoglobinopathies?

Answer 6

Autosomal recessive

Question 7

What is a thalassaemia?

Answer 7

Reduced glob in chain synthesis, leads to impaired haemoglobin production

Question 8

Two types of thalassaemia?

Answer 8

Alpha

Beta

Question 9

Alpha thalassaemia is a result of what?

Answer 9

Mutations affecting alpha globin chain synthesis

Question 10

The 3 types of alpha thalassaemia?

Answer 10

Trait
HbH disease
Hb Barts hyrops fetalis

Question 11

Gene situ in alpha thalassaemia trait?

Answer 11

One or two genes missing

Question 12

Gene situ in HbH disease ?

Answer 12

Only one alpha gene left

Question 13

Gene situ in Hb Barts hydrops fetalis ?

Answer 13

No functional alpha genes

Question 14

How do you distinguish alpha thalassaemia trait from iron deficiency?

Answer 14

Normal ferritin

Question 15

What happens to the excess beta chains in HbH disease?

Answer 15

The form tetramers which cannot carry oxygen

Question 16

Treatment of severe HbH disease?

Answer 16

Maybe need splenectomy +/- transfusion

Question 17

Can any HbA be made in Hb Barts hydrops fetalis?

Answer 17

No

Question 18

Beta thalassaemia is the result of what?

Answer 18

Disorder of beta chain synthesis

Question 19

What types of haemoglobin are affected in beta thalassaemia?

Answer 19

Only HbA as it is the only Hb that contains beta chains

Question 20

Which is the worst thalassaemia to have?

Answer 20

Alpha because it affects all types of haemoglobin - cannot substitute loss of HbA by making more of another

Question 21

When does beta thalassaemia major tend to present?

Answer 21

6-24 months old

Question 22

Why does beta thalassaemia major present at 6-24 months old?

Answer 22

Reduction in HbF so when trying to make HbA, realises there is a disorder in making the beta chains

Question 23

Haemoglobin analysis in beta thalassaemia major?

Answer 23

Mainly HbF

Minimal HbA

Question 24

Management of beta thalassaemia major?

Answer 24

Regular transfusion

Bone marrow transplant if be for complications develop

Question 25

Features of extramedullary haematopoiesis?

Answer 25

Hepatosplenomegaly Skeletal changes Organ damage

Question 26

Consequences of iron overload - endocrine

Answer 26

Impaired growth and pubertal development Diabetes Osteoporosis

Question 27

Consequences of iron overload - cardiac

Answer 27

Cardiomyopathy | Arrhythmias

Question 28

Consequences of iron overload - liver

Answer 28

Cirrhosis | Hepatocellular cancer

Question 29

Management of iron overload?

Answer 29

250mg of iron per unit of red cells | Iron chelating drugs - eg desferrioxamine

Question 30

How do iron chelating drugs manage iron overload?

Answer 30

Chelators bind to iron -> complexes form -> excreted in urine or stool

Question 31

What is the pathophysiology of sickling disorder?

Answer 31

Point mutation in codon 6 of beta globin gene - substitutes glutamine to valine -> Bs Alters Hb -> HbS HbS polymerises if exposed to low O2 -> distorts red cell, damaging RBC membrane

Question 32

Types of sickling disorder?

Answer 32

``` Sickle trait (HbAS) Sickle cell anaemia (HbSS) ```

Question 33

What happens in sickle cell trait?

Answer 33

One normal and one abnormal beta gene Asymptomatic Mainly HbA / <50% HbS

Question 34

What happens in sickle cell anaemia?

Answer 34

``` Two abnormal beta genes No HbA Sickle crisis Chronic haemolysis Hypospelnism due to repeated infarcts ```

Question 35

What happens in sickle crisis?

Answer 35

Sickle cell vaso-occlusion -> tissue ischaemia and sever pain

Question 36

Precipitants of sickle crisis?

Answer 36

``` Hypoxia Dehydration Infection Cold exposure Stress/fatigue ```

Question 37

Treatment of sickle crisis?

Answer 37

``` Opiate analgesia Hydration Rest Oxygen Antibiotics if evidence of infection Red cell exchange transfusion if severe ```

Question 38

Long term management of sickle crisis?

Answer 38

If hyposplenism- prophylactic penicillin and vaccinations to reduce risk of infection Folic acid supplementation Hydroxycarbamide can reduce severity of disease by inducing HbF production