Haemoglobulinopathies

Question 1

What is Haemoglobin made up of?

Answer 1

2 alpha globin like chains
2 Beta globin like chains
One haem group attached to each globin chain

Question 2

What are the three main types of haemoglobin?

Answer 2

HbA
HBA2
HbF

Question 3

What is HbA made of?

Answer 3

a2b2

Question 4

What is HbA2 made of?

Answer 4

a2d2

Question 5

What is HbF made of?

Answer 5

a2y2

Question 6

What % of Hb in adults is HbA?

Answer 6

97%

Question 7

Where are alpha like genes found?

Answer 7

chromosome 16

Question 8

How many alpha genes are found per chromosome/cell?

Answer 8

2 per chromosome

4 per cell

Question 9

How many beta genes are found per chromosome/cell?

Answer 9

1 per chromosome

2 per cell

Question 10

What chromosome are beta like genes found on?

Answer 10

Chromosome 11

Question 11

When are adult levels of Hb reached?

Answer 11

6-12 months of age

Question 12

What is affected in haemoglobulinopathies?

Answer 12

Globin chain synthesis

Question 13

What do haemoglobulinopathies behave as?

Answer 13

Autosomal recessive

Question 14

What are the two main groups of haemoglobulinopathies?

Answer 14

Thalassaemias

Structural haemoglobin variants

Question 15

What occurs in thalassaemias?

Answer 15

Decreased rate of globin chain synthesis

Question 16

What occurs in structural haemoglobin variants?

Answer 16

Normal production of abnormal globin chain

Question 17

what are the 2 types of thalassaemias?

Answer 17

Alpha

Beta

Question 18

What occurs in thalassaemia?

Answer 18

Inadequate Hb production

Microcytic hypochromic anaemia

Question 19

What happens in severe thalassaemia?

Answer 19

Unbalanced accumulation of globin chains
Haemolysis
Innefective erythropoeisis

Question 20

Where are thalassaemias more common?

Answer 20

Africa

Middle east

Question 21

What chains are affected in alpha thalassaemia?

Answer 21

A globin chain

Question 22

What alpha genes do unaffected individuals have?

Answer 22

aa/aa

Question 23

How does alpha thalassaemia occur?

Answer 23

Deletion of one A+ or bot A0 on chromosome 16

A-/AA) or (AA/–

Question 24

What HB are affected in Alpha thalassaemia?

Answer 24

All
HbA
HbA2
HbF

Question 25

What is alpha thalassaemia trait?

Answer 25

One or two alpha genes missing

Question 26

What is HbH disease?

Answer 26

Only one alpha gene (--/-a)

Question 27

What is Hb Barts hydrops fetalis?

Answer 27

No functional alpha genes

Question 28

What is alpha thalassaemia trait?

Answer 28

Asymptomatic carrier state Microcytic hypochromic red cells Mild anaeia

Question 29

What is the treatment or apha thalassaemia trait?

Answer 29

None needed

Question 30

What are the ferritin levels in alpha thalassaemia trait?

Answer 30

Normal

Question 31

What occurs in HbH disease?

Answer 31

Anaemia with very low MCV and MCH

Question 32

What is HbH?

Answer 32

Excess B chains form B4 called HbH

Question 33

What is the complication of HbH?

Answer 33

Jaundice Splenomegaly May need transfusion

Question 34

What is the severest form of A thalassaemia?

Answer 34

Hb barts hydrops foetalis syndrome

Question 35

What cannot be produced in Hb barts hydrops foetalis syndrome?

Answer 35

HbF and HbA

Question 36

What happens as there is no alpha chains in Hb barts hydrops foetalis syndrome?

Answer 36

``` Hb Barts tetramers (y4) HbH tetramers (B4) ```

Question 37

What can avoid risk of Hb barts hydrops foetalis syndrome?

Answer 37

Antenatal screening

Question 38

What are the clinical features of Hb barts hydrops foetalis syndrome?

Answer 38

``` Profound anaemia Cardiac failure Growth retardation Hepatosplenomegaly Skeletal abnormalities Cardiovascular abnormalities Almost all die in utero ```

Question 39

What are beta thalassaemias?

Answer 39

Disorders of beta chain synthesis

Question 40

What causes beta thalassaemias?

Answer 40

Usually caused by point mutations

Question 41

What are B+?

Answer 41

Reduced function

Question 42

What are B0?

Answer 42

Absent

Question 43

What Hb chains are affected in Beta thalassaemia?

Answer 43

Only HbA

Question 44

What is Beta thalassaemia trait?

Answer 44

B+/B or B0/B

Question 45

What happens in B thalassaemia trait:?

Answer 45

Asymptomatic No/mild anaemia Low MCV/MCH Raised HbA2

Question 46

What is B thalassaemia intermedia?

Answer 46

B+/B+ or B0/B+

Question 47

What is the treatment for B thalassaemia intermedia?

Answer 47

Occasional transfusion

Question 48

What is B thalassaemia major?

Answer 48

B0/B0 | Severe

Question 49

When does BTM present?

Answer 49

6-24months as HbF falls

Question 50

What are the symptoms of Beta Thalassaemia major?

Answer 50

Pallor | Failure to thrice

Question 51

What does extramedullary haematopoiesis cayse?

Answer 51

Hepatosplenomegaly Skeletal changes Organ damage Cord compression

Question 52

What is seen in haemoglobin analysis of BTM?

Answer 52

Mainly HbF | No HbA

Question 53

What is the management of B thalassaemia major?

Answer 53

Regular transfusion programme

Question 54

What level is Haemoglobin maintained in B thalassaemia major?

Answer 54

95-105g/l

Question 55

What do transfusions do in B thalassaemia major?

Answer 55

Suppresses ineffective erythropoiesis | Inhibits over-absorption of iron

Question 56

What is the main cause of death in B thalassaemia major?

Answer 56

Iron overload

Question 57

What are the consequences of iron overload?

Answer 57

``` Endocrine dysfunction -Impaired growth and pubertal development Diabetes Osteoporosis Cardiac disease -Cardiomyopathy -Arrhythmias Liver disease -Cirrhosis -Hepatocellular cancer ```

Question 58

What is the treatment of iron overload?

Answer 58

Iron chelating drugs

Question 59

What causes sickiling disorders?

Answer 59

Point mutation in codon 6 of the B globin gene that produces Bs Changes Hb to HbS HbS polymerises and distorts the red cell and damages the membrane

Question 60

What is sickle cell trait?

Answer 60

B/Bs

Question 61

What is sickle cell anaemia?

Answer 61

Two abnormal B genes (Bs/Bs)

Question 62

What is the % of HB that is HbS in sickle cell anaemia?

Answer 62

>80%

Question 63

WHat is sickle crisis?

Answer 63

Episodes of tissue infarction due to vascular occlusion

Question 64

What are the consequences of sickle cells anaemia?

Answer 64

Chronic haemolysis Sequestration of sickeled Rbcs in liver and spleen Hyposplenism -Repeated splenic infaracts

Question 65

What can precipitate sickle crisis?

Answer 65

``` Hypoxia Dehdration Infection cold exposure Stress/fatigue ```

Question 66

What is the treatment of sickle crisis?

Answer 66

``` Opiate analgesa Hydration Rest Oxygen Antibiotics if infected ```

Question 67

What is the long term management of sickle cell anemia/

Answer 67

Hyposplenism: Reduce infection risk - prophylactic penicllin and vaccinations Folic acid supplements Hydroxycarbamide Regular transfusion

Question 68

How are haemoglobinopathies diagnosed?

Answer 68

``` FBC Hb Red cell indicies Blood film Enthic origin HPLC (High performance liquid chromatography ```

Question 69

What is diagnostic of beta thalassaemia?

Answer 69

Raised HbA2

Question 70

What is seen on blood analysis of a normal patient?

Answer 70

HbA >80% HbF <1% HbA2 1.5-3.5%