Sickle cell disease

Question 1

what is a haemoglobinopathy and what are the two types?

Answer 1

A defect in the haemoglobin molecule and they are divided into:

Haemoglobin variants: 4 chains are present but structurally there is something wrong with the chains. Sickle cell is the main example.

Thalassaemias- There is a problem with the production of the haemoglobin leading to structurally normal haemoglobin with decreased or absent production.

Question 2

what are the chains and genes in normal haemoglobin?

Answer 2

Normal haemoglobin (HbA) consists of 2 alpha and 2 beta chains. This is made from 2 alpha and 4 beta globin genes.

Question 3

If you inherit normal alpha and beta globin genes what is your haemoglobin made up of?

Answer 3

94-98% HbA (normal),
2-4% HbA2,
0.8-2% HbF
0% HbS (sickle)

Question 4

What are the main categories of sickle cell?

Answer 4

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 5

what is the inheritance pattern of sickle cell?

Answer 5

A.Recessive

Question 6

what is the mutation in the beta globin gene causing sickle cell?

Answer 6

A point mutation on chromosome 11 causing valine to be swapped to glutamic acid

Question 7

How is sickle cell diagnosed?

Answer 7

New born heel test at day 5.

Antenatal screening by week 10 in high risk couples

Identification of the sickle erythrocytes: haemoglobin electrophoresis, DNA sequencing.

Question 8

what blood results are shown in sickle cell?

Answer 8

Raised reticulocytes, low haptoglobin and raised billirubin due to increased haemolysis

Blood film microscopy: sickle shaped erythrocytes and Howell- Jolly bodies (HJB only if hyposplenic).

Question 9

what are examples of acute crises?

Answer 9

• Vaso-occlusion
• Acute chest syndrome
• Aplastic crisis
• Hand foot syndrome

Question 10

what is vaso-occlusion?

Answer 10

This is an acute pain crisis.

The cells sickle causing blockage of multiple vessels and organs.

Question 11

what are symptoms and findings in an acute chest crisis?

Answer 11

Clinical features:

• SOB
• fever
• resp symptoms

Findings:

• new pulmonary infiltrate on CXR
• hypoxia

Question 12

what is the main management for acute chest syndrome?

Answer 12

Urgent exchange transfusion

Question 13

what is aplastic crisis?

Answer 13

Due to infection (mainly Parvovirus B19) there is a sudden hault to the production of RBC’s causing a sudden drop in Hb.

Question 14

What is hand-foot syndrome?

Answer 14

A crisis causing dactylitis which normally lasts for around a week.

Question 15

what are complications/features of sickle cell?

Answer 15

Jaundice
Dactylitis
Chronic organ damage
retinopathy
pulmonary HTN
priapism
stroke
avascular necrosis
sequestration
sepsis
increased susceptibility to encapsulated bacteria

Question 16

what factors can trigger a vaso-occlusive episode?

Answer 16

Hypoxia
dehydration
infection
cold exposure stress

Question 17

what investigations should be done for an acute painful presentation?

Answer 17

Bloods and ABG if chest signs
CXR
plain XR of line bones
ECG

Question 18

what are the categories of management for sickle cell?

Answer 18

Prevention
Acute complications
Chronic complications

Question 19

what is the ongoing management for sickle cell?

Answer 19

Long term Abx especially penicillin
Folic acid 5mg daily
Immunisations (seasonal influenza, 5 yr pneumococcal, meningitis and hep B)
Hydroxyurea (increases the amount of foetal Hb and helps RBC’s last longer than 20 days)

Question 20

what are the indications for hydroxyurea to be started?

Answer 20

More than 3 acute painful episodes needing admission
Acute chest syndrome needing transfusion/ high dependency unit
Previous stroke

Question 21

what is the management of an acute painful episodes?

Answer 21

ABCDE
Observations
Check sickle cell care plan
Fluids
Oxygen
Analgesia
Abx
Referral

Question 22

what is the management of acute chest syndrome?

Answer 22

ABCDE
Observations
Oxygen
Invasive spirometry (goal to prevent atelectasis)
Analgesia
Broad spec Abx as can't rule out bacterial pneumonia
Blood transfusion
Fluids

Question 23

what bacteria are sickle cell patients more at risk of?

Answer 23

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

Question 24

what is done for stroke prevention in younger patients with sickle cell?

Answer 24

Annual transcranial doppler ultrasounds to assess risk. If high risk they will be offered regular transfusions

Question 25

what are key questions to ask a patient who is presenting with an acute presentation of known sickle cell disease?

Answer 25

What is their diagnosis?
Do they have their care plan?
What is their preventative strategy ie hydroxyurea/exchange programme?
Last sickle percentage and haemoglobin baseline?

Question 26

what findings does an aplastic crisis find?

Answer 26

Sudden anaemia

low reticulocyte count