Sickle Cell Anaemia Flashcards
what is sickle cell disease (SCD)?
a group of disorders associated with the deformation of red blood cells into a sickled shape
what is sickle cell anaemia (SCA)?
- the most common and serious form of SCD
- SCA is caused by the inheritance of two abnormal sickle cell genes
what is the most common type of haemoglobin in the foetus and neonate?
HbF
what is the composition of HbF?
two alpha chains + two gamma chains
by what age does HbF production decrease to less than 1% of total haemoglobin?
by 6 months of age
what is the most common haemoglobin type in people older than 6 months?
HbA
what is the composition of HbA?
two alpha chains + two beta chains
what percentage of total haemoglobin in adults is HbA?
97%
what genetic inheritance pattern does sickle cell disease (SCD) follow?
autosomal recessive
what causes sickled haemoglobin (HbS) in SCD?
a single point mutation in the beta-globin gene leading to an amino acid change from glutamic acid to valine at position 6
what type of haemoglobin is present in individuals with sickle cell anaemia (SCA)?
HbSS
what haemoglobin type is found in individuals with sickle cell trait?
HbAS
what happens to sickled haemoglobin (HbSS) under physiological stress?
it polymerises causing erythrocytes to deform into a sickled shape
what are some physiological stressors that can induce sickling in HbSS?
- hypoxia
- dehydration
- infection
- cold
- acidosis (e.g. lactic acidosis)
when do clinical features of sickle cell anaemia (SCA) typically begin to appear?
- between 3- 6 months of age
- this is when HbF levels fall and the proportion of HbSS in the blood rises
what are the symptoms of SCA?
- acute or chronic pain (e.g. due to vaso-occlusion)
- features of anaemia (e.g. pallor, lethargy)
- growth restriction
- delayed puberty
- splenomegaly (e.g. due to increased haemolysis in the spleen)
- recurrent infections (e.g. pneumococcus, haemophilus influenzae type b, meningococcus and salmonella)
- jaundice
what is the most common reason for hospital admission among SCA patients?
- vaso-occlusive crises
- sickled RBCs obstruct the microcirculation, causing pain and ischemia +/- infarction
what is the second most frequent reason for hospitalization and a leading cause of death in SCA patients?
acute chest syndrome presents as new pulmonary infiltrates on the chest radiograph with one or more of the following manifestations:
- fever
- cough
- tachypnoea
- dyspnoea
- sputum production
- new-onset hypoxia
what are the potential causes of acute chest syndrome in patients with SCA?
- infection
- pulmonary infarction
- pulmonary embolism or pulmonary fat embolism (e.g. as a complication from bone marrow infarction)
what is an aplastic crisis?
- the temporary cessation of erythropoiesis, causing severe anaemia
- usually precipitated by infection with parvovirus B19
- patients may present with high-output congestive heart failure secondary to anaemia
- a transfusion is usually required but recovery may also occur spontaneously
what is a sequestration crisis?
- the sudden enlargement of the spleen due to haemorrhage within it
- associated with an acute drop in haemoglobin and a markedly raised reticulocyte count
- may lead to circulatory collapse and hypovolemic shock
- recurrent splenic sequestration is an indication for splenectomy
what are the findings on examination of SCA?
- conjunctival pallor +/- pallor
- dactylitis
- jaundice
- splenomegaly
what are the investigations for SCA?
- FBC (e.g. Hb 60-80g/L, with a high reticulocyte count of 10-20% is often normal for the patient)
- blood film (e.g. sickling of erythrocytes and features of hyposplenism including target cells and howell-jolly bodies)
- sickle solubility test (e.g. when blood with HbS is mixed with sodium dithionite a precipitate is formed and the solution becomes turbid)
- Hb electrophoresis
how is newborn screening for SCD conducted in the UK?
neonatal heel prick blood spots are collected 3 to 10 days after birth for haemoglobin analysis
what test is necessary to diagnose SCD/SCA, and what are the typical findings?
Hb electrophoresis
SCA: no HbA, 80-95% HbSS, 1-20% HbF
SCD: both HbA and HbS are present
what is the preventative management of SCA?
- avoidance of potential triggers (e.g. cold, dehydration, smoking)
- prevention of infection with antibiotics (e.g. oral penicillin prophylaxis, vaccinations)
- prevention of severe anaemia (e.g. folic acid supplementation)
what is the medical management of SCA?
- ‘top-up’ transfusions
- exchange transfusions (e.g. if there is concern about hyperviscosity associated with ‘top-up’ transfusion)
- iron chelation therapy
- hydroxycarbamide
- ? allogeneic bone marrow transplant
- gene therapy
what is the mechanism of action of hydroxycarbamide in SCA?
is a once-daily medication which increases HbF production and thus reduces the proportion of HbS in the blood
at what age is hydroxycarbamide offered to patients with SCA?
from 9 months old onwards
what is the management of a painful vaso-occlusive crisis?
- analgesia (e.g. paracetamol +/-NSAIDs)
- warmth
- rehydration
- rest
- patients should be admitted if strong opioids are required
what is a risk of inadequate management of painful crises, especially in the chest wall?
atelectasis due to the subsequent reduced respiratory effort (e.g. in an attempt to reduce to pain)
how does atelectasis contribute to complications in patients with SCA?
- increases the risk of LRTIs, which leads to reduced pulmonary ventilation in the affected lung area and hypoxia; which may lead to further sickling
- this vicious circle increases the risk of acute chest crisis which can cause critical illness and death
what screening method is recommended in children with SCA to identify those at higher risk of stroke?
transcranial doppler ultrasonography
what is the management of acute chest syndrome?
- oxygen
- consider continuous positive airway pressure, intravenous antibiotics, transfusion or exchange transfusion and ventilation if necessary
what are the long-term complications of SCD/SCA?
- chronic pain
- cardiac failure
- respiratory (e.g. chronic pulmonary disease, pulmonary hypertension)
- gallstones (e.g. due to increased haemolysis)
- eye (e.g. retinopathy, retinal infarcts, retinal haemorrhage, retinal detachment)
- transfusion-associated (e.g. iron overload, alloimmunisation)
- chronic leg ulcers
- AVN
- CKD
