Haematology - 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
What is a vaso-occlusive crisis?
AKA painful crisis
Most common type of sickle cell crisis
Sickle cells clog capillaries causing distal ischaemia
How does a vaso-occlusive crisis present?
Dactylitis (pain and swelling in hands or feet)
Can affect chest, back
Can be associated with fever
What is present on examination of a patient with a vaso-occlusive crisis?
Pallor- anaemia
Jaundice- haemolysis
Fever
Tachycardia
Tachypnoea
Digital redness, swelling and pain - inflammation
What are some differential diagnoses for a vaso-occlusive crisis?
Gout
Acute abdominal pain
- Pancreatitis
- Appendicitis
- Cholecystitis
If a vaso-occlusive crisis lasts more than 7 days what should be considered?
Other causes of bone pain e.g.
Osteomyelitis
Avascular necrosis
What usually causes vaso-occlusive crisis?
Strenuous exercise
Dehydration
Infection
Why does a vaso-occlusive crisis cause priapism?
Blood trapped in the penis, causes painful and persistent erection
How is priapism treated?
Urological emergency
Treated by aspirating blood from penis
How can SCD lead to hyposplenism?
Splenic sequestration crisis
RBCs block blood flow within spleen
Causes an acute enlarged and painful spleen
This can lead to splenic infarction leading to hyposplenism
What does blood pooling in the spleen due to splenic sequestration crisis lead to?
Severe anaemia
Hypovolaemic shock
What infections are more likely in hyposplenism?
Encapsulated bacteria
- Streptococcus pneumoniae
- Haemophilus influenzae
- Meningococcus
How are recurrent splenic sequestration crises prevented?
Splenectomy
What regular vaccinations should patients with a splenectomy receive?
- Seasonal flu vaccines
- Pneumococcal vaccines - every 5 years
- Meningococcal C vaccine
- Haemophilus influenza B vaccine
- Hepatitis B vaccine - if getting regular blood transfusions
What is an aplastic crisis?
Temporary absence of RBC production
What can trigger an aplastic crisis?
Parvovirus B19 infection
What does an aplastic crisis lead to?
Significant aplastic anaemia
How do you manage an aplastic crisis?
Supportive
Blood transfusions if necessary
Usually resolves within a week spontaneously
What is acute chest syndrome?
Vessels supplying lungs become clogged with RBCs
What causes acute chest syndrome?
Vaso-occlusive crisis
Fat embolism
Infection
How does acute chest syndrome present?
Fever
Shortness of breath
Chest pain
Cough
Hypoxia
What does a CXR show in acute chest syndrome?
Pulmonary infiltrates
How is acute chest syndrome managed?
Medical emergency with high mortality
Supportive management and treat underlying cause
- Analgesia
- IV fluids
- Antibiotics or antivirals for infections
- Blood transfusions for anaemia
- Incentive spirometry
- Respiratory support, oxygen, NIV or MV
How is SCD managed generally?
Specialist MDT
- Avoid triggers for crises e.g. dehydration
- Up-to-date vaccinations
- Antibiotic prophylaxis
- Hydroxycarbamide
- Crizanlizumab
- Blood transfusions
- Bone marrow transplant (can be curative)
What are blood transfusions used for prophylactically?
Maintain HbS < 30%
What is the typical antibiotic prophylaxis for infection?
Penicillin V
What does hydroxycarbamide do?
Stimulates HbF
HbF does not lead to sickling of RBCs
Reduces frequency of vaso-occlusive crises, improves anaemia and can extended lifespan
When can patients with SCD first present?
6 months old when HbF decreases
What is crizanlizumab?
Monoclonal antibody
Targets P-selectin
What is P-selectin?
Adhesion molecule found on endothelial cells on the inside walls of blood vessels and platelets
Prevents RBCs from sticking to blood vessel wall
Reduces frequency of vaso-occlusive crises
