BJA SCD Flashcards
BJA Edu - Sickle Cell disease
1 Sickle cell disease is an inherited disorder, with multisystem complications resulting from vaso-occlusion and chronic haemolysis.
2 Long-term management involves education; early vaccination and prophylaxis with penicillin; and prevention of end-organ damage.
3 Common life-threatening complications include infections, acute chest syndrome, splenic sequestration, and stroke.
4 Perioperative management involves careful planning and optimisation to ensure adequate oxygenation, hydration, tissue perfusion, and pain control.
5 Prompt pain assessment and multimodal analgesia are essential in treating acute painful events.
Genetics
Abnormal β-globin chain from both parents,
where at least one is the sickle cell gene.
Sickle cell anaemia (SCA), the most severe and common form of SCD,
results from inheriting sickle β-globin genes from both parents, leading to a homozygous HbSS state.
Other disease forms include heterozygous states involving other abnormal β-globin alleles such as β-thalassaemia (HbSß), C (HbSC), and D-punjabi (HbSD
one sickle cell and one normal haemoglobin gene leads to sickle cell trait (SCT), which usually has no clinical consequences
The WHO reports that the sickle cell gene is responsible for more than 80% of all inherited haemoglobinopathies, with 85% of SCD cases in Africa
The distribution of SCD closely matches the distribution of malaria, because the heterozygous states are protective against Plasmodium falciparum infection
neonatal screening, immunisation, and penicillin prophylaxis
Pathogenesis
HbA (containing two α and two β polypeptide chains) is the predominant haemoglobin type.
In sickle cell disorders, chromosome 11,
which codes for the β chain,
has a valine substituted for glutamic acid at codon 6;
this results in a hydrophobic β chain that tends
to polymerise at lower oxygen tensions
Polymers bundle together to create the red cell ‘crescent-shape’ causing microcirculatory occlusion.3 At birth, fetal haemoglobin (HbF) predominates containing γ rather than β chains.4 Therefore, haemoglobin is essentially normal and clinical features rare until the child begins to produce HbA at 4–6 months of age.
individual phenotypes are determined by other modifiers, and red blood cell sickling may not be the only pathology
Pathogenesis
HbA (containing two α and two β polypeptide chains) is the predominant haemoglobin type.
In sickle cell disorders, chromosome 11,
which codes for the β chain,
has a valine substituted for glutamic acid at codon 6;
this results in a hydrophobic β chain that tends
to polymerise at lower oxygen tensions
Polymers bundle together to create the red cell ‘crescent-shape’ causing microcirculatory occlusion.3 At birth, fetal haemoglobin (HbF) predominates containing γ rather than β chains.4 Therefore, haemoglobin is essentially normal and clinical features rare until the child begins to produce HbA at 4–6 months of age.
individual phenotypes are determined by other modifiers, and red blood cell sickling may not be the only pathology
Diagnosis
Universal newborn blood spot screening
Antenatal screening is also offered to all pregnant women.
After a positive result, the test is repeated using another of these techniques to confirm the diagnosis.
In SCA, full blood count shows low haemoglobin concentrations secondary to chronic haemolysis; high mean cell volume and red cell distribution width reflect early release of reticulocytes in response to anaemia
. Folate deficiency occurs because of high cell turnover and limited folate stores.
Chronic management
Complications
MDT
parent education, vaccination, and prophylactic penicillin before the expected fall in HbF concentrations.
cerebrovascular disease, heart failure secondary to thrombotic disease or pulmonary hypertension, and early signs of chronic kidney disease caused by ischaemic damage and loss of renal tubules
Protection against encapsulated organisms, particularly Streptococcus pneumoniae, is routine practice.
Vaccination
cludes vaccination against Haemophilus influenzae (Hib), Neisseria meningitidis (Men C), and hepatitis B.
hildren with SCD receive the pneumococcal, meningitis ACWY, the annual influenza vaccine, and an additional dose of HiB and Men C vaccines
Prophylaxis
Oral penicillin prophylaxis is continued from 3 months to 5 yr of age and significantly reduces pneumococcal infection
In endemic areas, malaria prophylaxis is also indicated.
Folate and micronutrient supplementation are also given routinely and these limit the consequences of rapid cell turnover.
HbF production can be prolonged pharmacologically with hydroxyurea
Acute complications
- Infection
- Vaso-occlusive episodes.
- Acute chest syndrome (acute CS)
- Splenic sequestration
- Stroke
Others
include priapism and renal tubular necrosis
- Infection
Multiple splenic microinfarcts secondary to sickling is an early complication of SCA, with 90% of affected children reported to have functional asplenia by age 6 yr.
isk of bacterial infections, most notably with S. pneumoniae in addition to atypical organisms
Parvovirus B19 is also an infective cause of acute complications in SCD, the most severe being aplastic crisis.
- Vaso-occlusive episodes.
Pain
Infection - hypoxia
- Acute chest syndrome (acute CS)
life-threatening complication of SCD defined as ‘an acute illness characterised by fever, respiratory symptoms, or both, accompanied by new pulmonary infiltrate on chest X-ray
Poor ventilation within the lung, which becomes hypoxic, with mismatching of ventilation and perfusion.
Hypoxia and acidosis then cause firstly sickling of red blood cells, leading adhesion of these sickle cells to other red blood cells, leukocytes and vascular endothelium, and secondly pulmonary vasoconstriction
Often the precipitant in children is infection, most commonly respiratory syncytial virus.
Treatment is supportive, using oxygen (high-flow humidified devices are particularly useful) and analgesia adequate to prevent hypoventilation.15 Broad-spectrum i.v. antibiotics with atypical cover are given and children should also receive a transfusion aiming for a haemoglobin concentration of 10 g dl
Procedures more common
Cholecystectomy
Gallstones occur in SCD secondary to chronic high circulating unconjugated bilirubin
Tonsillectomy and adenoidectomy
Hypertrophy of lymphoid tissues causing obstructive symptoms
Splenectomy
More than two episodes of splenic sequestration
Chronic hypersplenism with secondary pancytopaenia
Caesarean section Increased incidence of maternal and fetal complications in pregnancy including antepartum haemorrhage and delivery by caesarean section
Anaesthetic considerations
postoperative complications are vaso-occlusive episodes and acute CS
ostoperative sepsis is also a concern, but has substantially decreased since the introduction of early vaccinatio
The key to the anaesthetic management of children with SCD is planning and optimisation, ensuring adequate oxygenation, hydration, and pain control throughout the perioperative period.
Preop
- assess for complications of SCD including end-organ damage.
- Neutropenia is common as a complication of hydroxyurea therapy
- Haemoglobin electrophoresis may determine the percentage of HbS
- Urea and electrolyte measurement may reveal chronic kidney disease.
- Blood should be screened for antibodies and cross-matched blood made available
- multiple chest infections or acute CS, a chest X-ray and spirometry should be considered.
- Hydrated before surgery to decrease blood viscosity and the tendency for sickling.
first on the operating lis
- transfuse children presenting for low- or medium-risk surgery to the same protocol before surgery
(TAPS) - higher complications in not transfused patients
commonly receive an exchange transfusion or top-up transfusion, aiming for a preoperative haemoglobin concentration of 10 g dl−1 and Hb SS <30%
