Anaemia II

Question 1

THALASSAEMIA

• When would defects in the β genes manifest?
• When would defect in the α genes manifest?

What is a thalassaemia?

• Where are thalassaemias prevalent?

Answer 1

Only as of 6 months old

In foetal life, because HbF depends on α globin

Reduced or absent synthesis of one or more of the globin chains

In the central belt of the world

Question 2

What types of β thalassaemia are there + effect?

β thalassaemia trait (carrier)

β thalassaemia intermedia

β thalassaemia major

Answer 2

One normal
One faulty
Normal life, asymptomatic

Both faulty genes but not completely non-functional
Variable phenotype and life span.

Both faulty
Can’t make any HbA due to no Beta globin → death if untreated

Question 3

Pathophysiology of β thalassaemia major

Answer 3

No β chains so the α chains build up

You get extra-medullary haematopoiesis, where other organs (e.g. liver/spleen) try and take over and make RBCs, but also fail. Iron overload

Question 4

• What are the clinical features of β thalassaemia major?

why do you see on Xray ?

why do you get hepatosplenomegaly?

Answer 4

2. Anaemia in first few months of life (as HbA takes over)
3. Jaundice
4. Growth Retardation
5. Medullary hyperplasia (as bone marrow tries desperately to make RBCs) leading to:
   i. Facial changes due to medullary hyperplasia and frontal bossing
   ii. ‘Hair on end’ appearance of cranium due to medullary expansion
6. Splenomegaly/hepatomegaly (due to the extra-medullary haematopoiesis)

Question 5

• What does β thalassaemia major look like on a blood film?

Answer 5

2. Hypochromia (pale cells)

3. Target cells (with a little dot in the middle)

Question 6

• What is the treatment for β thalassaemia major?

what problem do you have to overcome with Tx?

Answer 6

1. Life long regular blood transfusions
   However, with transfusions – problem of iron overload.
2. Iron chelation (to prevent iron overload from transfusions)
3. Folic acid
4. Bone marrow transplantation in early life

Question 7

• What is β thalassaemia trait commonly mistaken for?

* What is the danger of this?

Answer 7

Iron-deficiency anaemia, because they also get a microcytic hypochromic anaemia; therefore. Differentiated from iron deficiency as they have an increase proportionally of HbA2 in B – thalassaemia.

That you give iron. This can do more harm than good in someone who isn’t iron deficient!

Question 8

α thalassaemia

o 1 in 4 genes mutated ?
o 2 in 4 genes mutated ?
o 3 in 4 mutated ?
o 4 in 4 mutated ?

Answer 8

o 1 in 4 genes mutated = silent carrier, asymptomatic.

o 2 in 4 genes mutated = asymptomatic trait,

o 3 in 4 mutated = haemoglobin H disease (not transfusion dependent but have some issues), reduced MCV/MCH, jaundice, hepatosplenomegaly, leg ulcers and gallstones.

o 4 in 4 mutated = haemoglobin Bart’s (can’t make HbF so 100% die in utero/stillborn)

Question 9

• How do we diagnose HbH disease?

How do we make diagnosis to know what genotype of alpha thalassaemia you are

Answer 9

Staining

DNA diagnosis

Question 10

SICKLING DISORDERS

• alpha or beta globin mutation?
• • What inheritance pattern do sickling disorders show?
• • What is the specific mutation leading to HbS?

• How does this change the haemoglobin protein?

Answer 10

are inherited Beta globin mutation.

autosomal recessive

Substitution mutation at the 6th amino acid of the β-globin protein (Glu → Val)

o This forms long inflexible strings of HbS
o This alters the shape of the RBCs into the characteristic sickle shape

Question 11

• How do normal RBCs compare to sickle RBCs?

Shape
Flexibility
Life span

Answer 11

Normal RBCs
Biconcave disc
Deformable
120 days

Sickle RBCs
Sickle shaped
Rigid – hence they get stuck in small vessels → ischamia
<20 days

Question 12

What is the clinical features of sickle cell anaemia?

Answer 12

1. Haemolysis (due to decreased life span) leading to:
   i. ⇑reticulocytes
   ii. ⇑ LDH
   iii. Anaemia (⇓Hb)
2. Vaso-occlussion leading to acute and chronic problems
3. Hyposplenism → risk of infection

Question 13

• What emergencies are there in people with sickle cell anaemia?

Acute chest syndrome = get pulmonary infiltrate - requires what ?

Neurological deficits - get stroke - requires what?

Infection - what is given to prevent this?

Acute splenic sequestration - spleen rapidly expands?

Answer 13

Requires close monitoring and potentially a transfusion to ⇓ the % of HbS

Ischaemic – more common in children and elderly, haemorrhagic more common in 20-29 yr olds. Difficult to be picked up as these patients don’t present like usual stroke victims
Needs usual stroke care and a transfusion to ⇓ the % of HbS

Prophylactic penicillin is used to prevent this

Spleen rapidly expands and Hb drops rapidly

Question 14

Why are transfusions rarely used in sickle patients early on like in thalassaemias?

Answer 14

don’t know how affected the individual will be

They are reserved for emergencies mentioned above.

Question 15

• What is HPLC? (High pressure liquid chromatography )

Answer 15

a lab test to look for haemoglobinopathies where you separate the different types of Hb to see if there are any odd types of Hb.

Question 16

• What is the sickle cell solubility test?

o When you hold the test tube up and compare it to a normal sample, you can see that it is what? - hence showing HbS is present

Answer 16

o A simple, cheap, crude screening test for sickle cell anaemia

cloudier - insoluble in phosphate buffers