Sickle cell disease (CH) Flashcards
Define sickle cell anaemia.
Caused by an autosomal recessive single gene defect in the beta chain of haemoglobin, resulting in the production of sickle cell haemoglobin (HbS)
What specific mutation happens in sickle cell anaemia?
Valine (non-polar) replaces glutamic acid (polar) at the 6th amino acid of the beta globin chain
How does the amino acid change in HbS explain the symptoms that occur in sickle cell anaemia?
Valine can fit into the hydrophobic pocket of another HbS molecule –> haemoglobin polymerises within the RBC –> long stiff fragile fibres of Hb tetramers
What is sickle cell trait vs sickle cell anaemia?
- sickle cell trait - HbS is inherited from one parent and normal HbA from the other
- sickle cell anaemia - sickle gene inherited from each parent
What are the different haemoglobins in normal vs sickle cell trait vs sickle cell anaemia?
- normal: HbAA
- carrier (sickle cell trait): HbAS
- sickle cell anaemia: HbSS
What % of black people carry the sickle cell gene?
8%
When does sickle cell anaemia typically present?
Presents after 6 months of age as the production of HbF decreases and HbS levels increase
What is the typical presentation of sickle cell anaemia?
Hand-foot syndrome = swelling, pain (crying baby), erythema in hands and feet
In which regions of the world is there positive selection for the sickle cell gene mutation?
Endemic regions for malaria as sickle cell trait/disease offers a protective effect against malaria
What are RBCs containing HbS like?
Rigid and distorted into a crescent shape
What can sickle cells cause?
Can cause occlusion of small vessels or adhere to vascular endothelium –> reduced blood flow and hypoxia –> more sickling and occlusion
What are sickle cells prone to?
Haemolysis - reduced RBC survival (around 20 days)
How do sickle cells cause anaemia?
Obstructs blood flow + breaks down prematurely –> anaemia
What factors precipitate sickling (sickle cell anaemia)? (7)
HADICSS
- hypoxia (HbAS sickle at pO2 2.5-4kPa, HbSS at pO2 5-6kPa)
- acidosis
- dehydration
- infection
- cold temperatures
- strenuous exercise
- stress
What are the clinical features of sickle cell anaemia? (10)
- bone pain / persistent pain in bones, chest, abdomen
- dactylitis (painful dorsa of hands and feet)
- anaemia Sx - tiredness, SOB, pallor
- high temperature
- pneumonia-like syndrome (sickling in pulmonary vessels)
- tachypnoea
- tachycardia
- jaundice
- splenomegaly in early disease (atrophy in late disease)
- visual floaters (sickling and occlusion of small retinal arterioles –> neovascularisation, cotton wool spots)
Are sickle cell carriers symptomatic?
Only if severely hypoxic
What crises are there in sickle cell anaemia? (4)
- vaso-occlusive crisis (persistent pain in skeleton, chest or abdomen)
- splenic sequestration (splenomegaly)
- acute chest syndrome (most dangerous)
- gallstones, chronic cholecystitis
Why do vaso-occlusive crises (causing persistent pain in skeleton, chest or abdomen) occur in sickle cell anaemia?
Sickle cells are fragile and haemolyse, which block small blood vessels and cause infarction
Why does splenic sequestration (–> splenomegaly) occur in sickle cell anaemia?
Sickle cells block blood vessels leading out of the spleen –> pooling of blood in the spleen (splenomegaly and low blood count) –> undergoes phagocytosis –> functional hyposplenism causing reduced immune function (increased risk of infections)
What is acute chest syndrome (sickle cell crisis)?
- pain, fever and respiratory symptoms e.g. dyspnoea, wheeze and cough
- caused by pulmonary infiltrates which can be seen on CXR
How do we manage acute chest syndrome (sickle cell anaemia)?
Attack On (A) Titan
- Analgesia
- Oxygen
- Antibiotics
- Transfusion
How do we manage gallstones and chronic cholecystitis due to sickle cell anaemia?
Cholecystectomy
What is the main risk factor for sickle cell anaemia?
Genetic - 25% chance of SCA if both parents are carriers
Which presentation of sickle cell anaemia can be diagnosed clinically?
Acute painful vaso-occlusive crisis
What is the gold-standard investigation for sickle cell anaemia?
Haemoglobin electrophoresis
What would haemoglobin electrophoresis show in sickle cell anaemia? (3)
- HbS
- no HbA
- raised HbF
What would a blood film show in sickle cell anaemia? (4+2)
- sickle cells
- nucleated RBCs
- anisocytosis
- features of hyposplenism: Howell-Jolly bodies, target cells
What would FBC show in sickle cell anaemia?
- anaemia - haemolytic
- elevated reticulocyte count in haemolytic (sequestration) crises
- may be low in aplastic crises (parvovirus B19)
What are sequestration crises characterised by? (2)
- high reticulocytes (haemolytic anaemia)
- splenomegaly
Why would you request an iron study in sickle cell anaemia?
To distinguish haemolytic anaemia from IDA
What does cellular acetate electrophoresis show in sickle cell anaemia vs sickle cell trait?
- sickle cell anaemia: 75-95% HbS, absent HbA
- sickle cell trait: 40% HbS, 60% HbA, <2% HbF
What are some differential diagnoses for sickle cell anaemia? (10)
- gout - can be seen in those with SCD
- septic arthritis
- connective tissue diseases
- avascular necrosis - hip/shoulder, differentiated from vaso-occlusive crisis by chronicity
- Perthe’s disease
- acute abdomen
- osteomyelitis
- trauma
- Parvovirus B19
- IDA
How do we manage an acute vaso-occlusive crisis (sickle cell anaemia)? (5)
F*ck Attack On (A) Titan:
- Fluids
- Analgesia (paracetamol, weak opioids +/- antihistamine if pruritus)
- Oxygen
- Antibiotics - if infection suspected
- Transfusion - if Hb low (<20)
What can we do if sickle cell crisis does not resolve, or if patient presents with stroke?
Exchange therapy - reduces sickle cells and increases normal cells
How do we manage chronic sickle cell anaemia?
- hydroxycarbamide / hydroxyurea - increases HbF which reduces frequency and duration of crises
- repeated blood transfusions - maintain HbS<30%
- infection prophylaxis (regular vaccinations) - particularly against encapsulated bacteria e.g. Pneumococcus due to hyposplenism
What vaccine should patients with sickle cell anaemia receive?
Pneumococcal polysaccharide vaccine every 5 years
What do we do for repeated splenic sequestration crises in sickle cell anaemia?
Splenectomy
How do we manage acute chest syndrome (sickle cell anaemia)? (4)
Attack On (A) Titan:
- Analgesia
- Oxygen
- Antibiotics
- Transfusion
What are some complications of sickle cell anaemia? (8)
- aplastic crises
- anaemia
- liver complications and cholelithiasis
- avascular necrosis
- dactylitis
- leg ulcers
- cardiovascular manifestations
- priapism (prolonged erection)
What are aplastic crises (sickle cell anaemia)?
Aplastic crises due to infection with parvovirus B19 which can lead to temporary cessation of erythropoiesis –> sudden drop in Hb and reduced reticulocytes
What is the median survival for sickle cell anaemia?
58 years
