Haem - Sickle Cell Anaemia Flashcards
How is sickle cell anaemia inherited?
Autosomal recessive
What gene is affected in sick cell?
Beta-globin gene on chromosome 11
Responsible for the beta hb subunit
What does the HbS allele result from?
Single nucleic acid substitution
GAG to GTG
In the beta globin coding gene
What does a GAG to GTG result in?
Glutamic acid substitution to Valine
Why does sickling occur in the deoxygenated state?
HbS tetramers bind to each other, this leads to polymerisation
This causes growth into long fibres which distort the shape of the RBC
In SCD gene carriers what is the expected amount of different haemoglobins?
HbA 60%
HbS 40%
How is sickle cell related to malaria?
More common in patients from areas traditionally affected by malaria e.g. Africa, India, Middle East and Caribbean
Sickle cell trait reduced severity of malaria
Patients with sickle cell trait more likely to survive to pass genes on, therefore selective advantage in areas of malaria
What is the incidence of SCD in Black, Asian and White people?
Black
1/200 affected
1/10 carriers
Asian
1/6,000 affected
1/60 carriers
White
1/90,000 affected
1/600 carriers
How is sickle cell disease screened for?
New born blood spot
When is new born heel prick test done?
5 days of age
When are pregnant women offered sickle cell testing?
When they are at higher risk of being a carrier of the gene
Why is the burden of SCD set to increase?
Higher survival rates among infants
Increased HbS prevalence in high-income countries
What investigations are used for SCD?
Haemoglobin electrophoresis - detects HbA absence
Blood film
FBC and reticulocyte count
X-ray of long bones- confirm presence of bone infarctions
CXR - infiltrates
What are the complications of SCD?
Anaemia
Increased infection risk
CKD
Sickle cell crises
Acute chest syndrome
Stroke
Avascular necrosis
Pulmonary hypertension
Gallstones
Priapism
What joints are affected by avascular necrosis in SCD?
Large joints such as the hip
What happens in sickle cell crisis?
Acute exacerbation caused by SCD, range from mild to life-threatening
What causes a sick cell crisis?
Spontaneous
Dehydration
Infection
Stress
Cold weather
How is sickle cell crisis managed?
Supportive management
- Low hospital admission threshold
- Treating infections that triggered crisis
- Keep warm
- Good hydration, may need IV fluids
- Analgesia, avoid NSAIDs in renal impairment