Haemoglobulinopathies

Question 1

What are the 2 Haemoglobulinopathies that we are going to discuss?

Answer 1

Sickle cell anaemia and Thalassaemia

Question 2

What is a haemoglobulinopathy?

Answer 2

Hereditary condition involving an abnormality in the structure of haemoglobin, in other words a structurally abnormal globulin chain

Question 3

How is Sickle cell anaemia inherited?

Answer 3

Autosomal Recessive fashion

Question 4

So if there are 2 carrier parents of SCD what is the chance of an effected child and a carrier child?

Answer 4

1 in 4

1 in 2

Question 5

What do the Hb chains look like in SCD?

Answer 5

2 alpha chains and 2 Beta sickle chains

Question 6

w=What is the basic pathophysiology in SCD?

Answer 6

RBCs contain Hbs, when when the cells become oxygenated they sickle, when they re-oxygenate again they DO nOT return to their normal biconcave shape and therefore cannot carry as much oxygen

Question 7

What is HbSS polymerisation?

Answer 7

There is red cell damage, cation loss and dehydration leading to haemolysis
This causes endothelial activation, inflammation, activation of coagulation, dysregulation of vasomotor tone and then VASO-OCCLUSION

Question 8

What is the prevalence and the affected group in SCD?

Answer 8

1/700 of those form an African heritage

Question 9

What are the features of a SCD crises?

Answer 9

Vaso-occlusove crises: causes severe pain in the bones
Chest crises: Chest pain, fever and worsening hypoxia
Stroke, infections, aplastic crises after parvovirus

Question 10

What are other clinical findings of SCD?

Answer 10

Retinopathy
Cerebral infarcts
Cardiomegalu and congestive HF
Pulmonary infarcts and pneumonia
Splenomegaly
Ulcers
Bone necrosis

Question 11

What is THE diagnostic test f SCD?

Answer 11

Sickle cells disease

Often high Bilirubin

Question 12

What tests are you going to do un a crises?

Answer 12

CXR infiltrates

Infection: blood cultures and parvovirus B19 screen

Question 13

What is the long-term prophylaxis of SCD?

Answer 13

Vaccinations
Penicillin and anti-malarial
Folic acid
Sometimes blood transfusion 
DMD: hydroxycarbimide 
Only cure is BONE MARROW TRANSPLANT

Question 14

What is the management of general crises?

Answer 14

Hydration 
Oxygenation 
Prompt treatment of infection 
analgesia
Thromboprophylaxis

Question 15

What is the management of a bone Crises?

Answer 15

Give analgesia within 30 mins of presentation

Hydration and oxygenation

Question 16

What is the management of a chest crises?

Answer 16

Respiratory support, antibiotics and IV fluids’ analgesia and transfusion

Question 17

What is the life prognosis of someone with SCD?

Answer 17

Decrease in life expectancy
M = 42yo
F = 48yo
Most live to 18

Question 18

What is the defining features of thalassaemia’s?

Answer 18

This is a haemoglobulinopaty where there is abnormal or no production of one of the globulin chains causing haemolysis whilst the cells are still in the bone marrow

Question 19

What are the 2 types of thalassaemias

Answer 19

Alpha and Beta

Question 20

What do the chains look like in alpha?

Answer 20

• α/αα “α+”: one alpha gene gone

- -/αα “α0”: both gone

Question 21

What are betaT’s usually caused by?

Answer 21

A point mutation in the beta globulin on chromosome 11, causing lack of beta chain

Question 22

What are the defining features of beta thalassaemia major?

Answer 22

Severe anaemia 
Presents at 3-6 months of age 
Expansion of ineffective bone marrow 
Bone deformities 
Splenomegaly 
Growth retardation

Question 23

What are the 2 types of beta thalassaemias?

Answer 23

Minor and major

Question 24

What is the diagnostic test of thalassaemia?

Answer 24

Hypochromic Microcytic RBC’s with NORMAL ferritin

Question 25

How are you going to treat major BetaT?

Answer 25

Chronic transfusion support:
o 4-6 weekly for normal growth and development
o Combine w/ iron chelation therapy to PREVENT OVERLOAD e.g. s/c DESFERRIOXAMINE INFUSIONS or oral DEFERASIROX
The curative treatment is bone marrow transplant

Question 26

What is the life expectancy?

Answer 26

Life expectancy if untreated or infrequent transfusions <10 years