Haemoglobinopathies

Question 1

When does homozygous sickle cell anaemia (HbSS) first present?

Answer 1

Usually in early childhood with anaemia + jaundice due to chronic haemolytic anaemia

Painful hands + feet w/ inflammation of fingers due to dactylitis

Question 2

What are precipitants of having a chest crisis?

Answer 2

Dehydration

Infection (eg. sore throat)

Cold or damp conditions

Unaccustomed exercise

Stress

Pregnancy

Operations

Question 3

What is the management of a chest crisis?

Answer 3

• hosp admission
• IV fluids, oxygen, adequate analgesia
• infection should be treated w/ antibiotics
• definitive investigation is haemoglobin electrophoresis which will demonstrate HbS, absent HbA, and variable HbF level
• exchange transfusion may be needed to reduce level of his sickle cells to less than 30%
• may benefit from long-term hydroxyurea which raises the HbF level + reduces number of crises

Question 4

What are haemoglobinopathies?

Answer 4

• caused by an abnormality in globin chain structure
• caused by single gene disorders
• most common = sickle cell diseases
• there are others eg. congenital dyserythropoietic anaemia (CDA)

Question 5

What are thalassaemias?

Answer 5

Absent or reduced alpha or beta globin chains which form the normal adult HbA (a2b2)

Caused by mutations in regulatory genes

Might overlap with haemoglobinopathies: HbS/beta-thalassaemia

Question 6

Genetics of sickle cell disease

Answer 6

Point mutation in the beta globin gene on chromosome 11

Amino acid substitution (adenine to thymine)

Causes glutamic acid being substituted by valine at position 6

Different mutations in beta globin chain structure lead to diff types of haemoglobin eg. HbD, HbC, HbE

Question 7

How do you take a sickle history?

Answer 7

Question 8

What are the chains and genes in normal haemoglobin?

Answer 8

Normal haemoglobin (HbA) consists of 2 alpha and 2 beta chains

This is made from 2 alpha and 4 beta globin genes

Question 9

What are the main categories of sickle cell disease?

Answer 9

1. Homozygous sickle cell anaemia:

Inherit the abnormal sickle gene from both parents so phenotype is HbSS

2. Heterozygous mutation (sickle cell disease):
   Inherit two different recessive alleles one of the sickle gene and the other another haemoglobin variant of the beta globin gene
3. Sickle-thalassaemia:
   Inherit a sickle gene and a thalassaemia gene causing abnormal production and structure - severity depends on which thalassaemia gene is inherited

Sickle cell trait:

Inherits a single sickle copy and rarely causes symptoms (a carrier)

Question 10

Inheritance pattern of sickle cell disease

Answer 10

Autosomal recessive

Question 11

How is sickle cell diagnosed?

Question 12

Blood results in sickle cell

Question 13

Examples of acute sickle cell crises

Answer 13

Vaso-occlusion

Acute chest syndrome

Aplastic crisis

Hand foot syndrome

Question 14

What is vaso-occlusive crisis?

Question 15

Symptoms and findings in an acute chest crisis

Question 16

Management of acute chest syndrome

Answer 16

Exchange transfusion

Question 17

What is an aplastic crisis?

Question 18

What is hand-foot syndrome?

Question 19

Complciartions of sickle cell disease

Answer 19

Jaundice
Dactylitis
Chronic organ damage
Retinopathy
Pulmonary HTN
Priapism
Stroke
Avascular necrosis
Sequestration
Sepsis
Increased susceptibility to encapsulated bacteria

Question 20

Ongoing management for sickle cell disease

Question 21

Indications for hydroxyurea in sickle cell disease

Answer 21

More than 3 acute painful episodes needing admission

Acute chest syndrome needing transfusion/HDU

Previous stroke

Question 22

Which bacterial infections are sickle cell patients more susceptible to?

Answer 22

Encapsulated such as H.influenzae and Strep pneumoniae due to hyposplenism

Question 23

What is alpha thalassaemia?

Question 24

What is beta thalassaemia?

Answer 24

A thalassaemia leading to reduced/absent production of the beta globin chains

Question 25

Inheritance pattern of thalassaemia

Answer 25

Autosomal recessive

Question 26

What mutation most commonly leads to alpha thalassaemia?

Question 27

Types of alpha thalassaemia

Answer 27

1. Alpha thalassaemia minima (aa/a-)
2. Alpha thalassaemia trait (a-/a-)
3. Haemoglobin H disease (a-/–)
4. Bart’s syndrome (–/–)