Thalassaemia & SCA

Question 1

Define Thalassaemia

Answer 1

Genetic defect in the protein chains that make up haemoglobin

Question 2

Defects in alpha-globin chains lead to..

Answer 2

Alpha thalassaemia

Question 3

Defects in the beta-globin chains lead to..

Answer 3

Beta thalassaemia

Question 4

Both thalassaemia conditions are autosomal dominant/ recessive

Answer 4

Recessive

Question 5

Explain the pathophysiology of thalassaemia

Answer 5

The RBCs are more fragile and break down easily, causing haemolytic anaemia. The spleen acts as a sieve, filtering the blood and removing older cells, it collects all the destroyed red blood cells, resulting in splenomegaly

Question 6

Microcytic anaemia (low mean corpuscular volume)

Answer 6

Thalassaemia

Question 7

Raised ferritin on Thalassaemia suggests..

Answer 7

Iron overload

Question 8

Ix for Thalassaemia

Answer 8

FBC
Haemoglobin electrophoresis for globin abnormalities
DNA testing for genetic abnormality

Question 9

Iron overload may occur in thalassaemia due to..

Answer 9

Increased iron absorption in the gastrointestinal tract
Blood transfusions

Question 10

Iron overload in thalassaemia can cause symptoms and complications of..

Answer 10

Liver cirrhosis
Hypogonadism
Hypothyroidism
Heart failure
Diabetes
Osteoporosis

Question 11

For iron overload, serum _____ levels are monitored. Management involves __________ and __________

Answer 11

For iron overload, serum ferritin levels are monitored. Management involves limiting transfusions and iron chelation

Question 12

The genes that code for alpha-globin are found on chromosome..

Answer 12

16

Question 13

The severity of symptoms in thalassaemia varies depending on the type and number of genetic defects. What are these?

Answer 13

Carrier
Moderate anaemia (haemoglobin H disease)
Intrauterine death due to severe fetal anaemia (alpha thalassemia major)

Question 14

Mx for alpha thalassaemia

Answer 14

Monitoring
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative

Question 15

If 1 or 2 alpha globulin alleles in alpha-thalassaemia are affected then the blood picture would be…

Answer 15

Hypochromic and microcytic, but the Hb level would be typically normal

Question 16

If there are 3 alpha globulin alleles affected in alpha-thalassaemia it results in..

Answer 16

Hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease

Question 17

f all 4 alpha globulin alleles are affected in alpha-thalassaemia (i.e. homozygote) then it results in..

Answer 17

Death in utero (hydrops fetalis, Bart’s hydrops)

Question 18

The gene coding for protein chains in beta-thalassaemia is on chromosome..

Answer 18

11

Question 19

In beta-thalassaemia, the gene defects can either consist of..

Answer 19

Abnormal copies that retain some function or deletion genes with no function in the beta-globin

Question 20

Beta-thalassaemia can be split into three types..

Answer 20

Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major

Question 21

What is Thalassaemia Minor?

Answer 21

Carriers of an abnormally functioning beta-globin gene. They have one abnormal and one normal gene. Causes mild microcytic anaemia and usually only requires monitoring

Question 22

What is Thalassaemia Intermedia?

Answer 22

Two abnormal copies of the beta-globin gene. This can be either:

Two defective genes
One defective gene and one deletion gene

Question 23

Mx for Thalassaemia Intermedia

Answer 23

Significant microcytic anaemia so require monitoring and may need occasional blood transfusions. May require iron chelation to prevent iron overload

Question 24

What is Thalassaemia Major?

Answer 24

Most severe form. Homozygous for the deletion genes. They have no functioning beta-globin genes

Question 25

Why does Thalassaemia Major causes fractures?

Answer 25

The bone marrow is under so much strain to produce extra red blood cells to compensate for the chronic anaemia that it expands enough to increase the risk of fractures and change the patient’s appearance

Question 26

Abnormal features relating to bone changes in Thalassaemia Major include..

Answer 26

Frontal bossing (prominent forehead) Enlarged maxilla (prominent cheekbones) Depressed nasal bridge (flat nose) Protruding upper teeth

Question 27

Mx for Thalassaemia Major

Answer 27

Repeated transfusions and splenectomy. A bone marrow transplant can be curative Transfusion can lead to iron overload → organ failure. So iron chelation therapy is important (e.g. desferrioxamine)

Question 28

Mild hypochromic, microcytic anaemia. It is usually asymptomatic HbA2 raised (> 3.5%)

Answer 28

Beta thalassaemia trait

Question 29

What is sickle cell anaemia?

Answer 29

Genetic condition that causes sickle (crescent) shaped red blood cells. This makes it more fragile and easily destroyed leading to haemolytic anaemia

Question 30

Patients with sickle cell anaemia are prone to..

Answer 30

Various sickle cell crises

Question 31

Patients with sickle-cell disease have an abnormal variant called..

Answer 31

Haemoglobin S (HbS)

Question 32

Sickle cell disease is more common in patients from areas traditionally affected by..

Answer 32

Malaria, such as Africa, India, the Middle East and the Caribbean

Question 33

T or F: Having one copy of the gene (sickle cell trait) reduces the severity of malaria

Answer 33

True - patients with sickle cell trait are more likely to survive malaria and pass on their genes. Therefore, there is a selective advantage to having the sickle cell gene in areas of malaria, making it more common.

Question 34

Screening for Sca

Answer 34

Newborn blood spot screening test at around five days of age Pregnant women at high risk of being carriers of the sickle cell gene are offered testing

Question 35

What is Sickle cell crisis?

Answer 35

Spectrum of acute exacerbations caused by sickle cell disease. These range from mild to life-threatening. They can occur spontaneously or triggered by dehydration, infection, stress or cold weather

Question 36

Symptoms in homozygotes SCA don't tend to develop until..

Answer 36

4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin

Question 37

Some patients inherit one HbS and another abnormal haemoglobin (HbC) resulting in..

Answer 37

Milder form of sickle cell disease (HbSC)

Question 38

Pathophysiology of SCA

Answer 38

Polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6). This decreases the water solubility of deoxy-Hb In the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle

Question 39

Definitive diagnosis of sickle cell disease is by..

Answer 39

Haemoglobin electrophoresis

Question 40

Long term mx for SCA

Answer 40

Hydroxyurea - increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes Sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years

Question 41

Type of sickle cell crises

Answer 41

Thrombotic, 'vaso-occlusive', 'painful crises' Acute chest syndrome Anaemic - aplastic, sequestration Infection

Question 42

What causes thrombotic crises?

Answer 42

Infection, dehydration, deoxygenation (e.g. high altitude)

Question 43

Ix for thrombotic crises

Answer 43

Diagnosed clinically

Question 44

What is acute chest syndrome?

Answer 44

Vaso-occlusion within the pulmonary microvasculature → infarction in the lung parenchyma

Question 45

Dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, low pO2

Answer 45

Acute chest syndrome

Question 46

Mx of acute chest syndrome

Answer 46

Pain relief Respiratory support e.g. oxygen therapy Antibiotics: infection may precipitate acute chest syndrome and the clinical findings (respiratory symptoms with pulmonary infiltrates) can be difficult to distinguish from pneumonia Transfusion: improves oxygenation

Question 47

The most common cause of death after childhood

Answer 47

Acute chest syndrome

Question 48

What causes aplastic crises?

Answer 48

Caused by infection with parvovirus

Question 49

Sudden fall in haemoglobin

Answer 49

Aplastic crises

Question 50

In an aplastic crises, ______________ causes a reduced reticulocyte count

Answer 50

Bone marrow suppression

Question 51

What is Sequestration crises?

Answer 51

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

Question 52

Sequestration crises is associated with a decreased/increased reticulocyte count

Answer 52

Increased

Question 53

Mx for sickle-cell crises

Answer 53

Analgesia e.g. opiates Rehydrate Oxygen Consider antibiotics if evidence of infection Blood transfusion

Question 54

When is exchange transfusion indicated in sickle cell crises?

Answer 54

Acute vaso-occlusive crisis (stroke, acute chest syndrome, multiorgan failure, splenic sequestration crisis) It rapidly reduce the percentage of Hb S containing cells

Question 55

When is blood perfusion indicated in sickle cell crises?

Answer 55

Severe or symptomatic anaemia, pregnancy, pre-operative Do not rapidly reduce the percentage of Hb S containing cells exchange transfusion

Question 56

Pain and swelling in the hands or feet but can affect the chest, back, or other body areas. It can be associated with fever It can cause priapism in men by trapping blood in the penis, causing a painful and persistent erection

Answer 56

Vaso-occlusive Crisis

Question 57

Hypovolaemic shock occurs secondary to which type of SCA crises?

Answer 57

Splenic Sequestration Crisis

Question 58

A vaso-occlusive crisis, fat embolism or infection can trigger..

Answer 58

Acute Chest Syndrome

Question 59

Which medications are used in Acute Chest Syndrome?

Answer 59

Hydroxycarbamide (stimulates HbF) Crizanlizumab (targets P-selectin)

Question 60

T or F: In alpha thalassaemia, α chains are present in HbA, HbA2 and HbF therefore all are affected

Answer 60

True

Question 61

Excess β chains form tetramers (β4) called..

Answer 61

HbH

Question 62

One or two alpha genes missing

Answer 62

α thalassaemia trait

Question 63

Only one alpha gene left

Answer 63

HbH disease

Question 64

No functional α genes

Answer 64

Hb Barts hydrops fetalis

Question 65

β+/β or β0/β

Answer 65

β thalassaemia trait

Question 66

β+/β+ or β0/β+

Answer 66

β thalassaemia intermedia

Question 67

β0/β0

Answer 67

β thalassaemia major

Question 68

β thalassaemia major leads to Extramedullary haematopoiesis which can cause..

Answer 68

Cord compression

Question 69

Mx of iron overload

Answer 69

Iron chelating drugs (eg desferrioxamine)

Question 70

Hb→ HbS (α2βs2)

Answer 70

Sickling disorder

Question 71

β/βs

Answer 71

Sick cell trait

Question 72

βs/βs

Answer 72

SCA

Question 73

Chronic haemolysis + hyposplenism

Answer 73

SCA