Haemoglobinopathies
Key points
Normal adult Hb (HbA) has 2 copies of α & β globin genes - chains
HbA2 - small amounts has 2 copies of α & δ globin genes - chains
Foetal Hb (HbF) has 2 copies of α & γ globin genes - chains
Gamma γ
Delta δ
Sickle cell disease
Sickle cell: 2 substitutions in β globin gene (chromosome 11) = HbS
Autosomal recessive
Heterozygous mutation - 'Sickle cell trait'
Homozygous mutation - moderate to severe phenotype with crises
10-15,000 in UK
1:365 black population
1: 16,000 hispanic population
Chronic haemolytic anaemia
Sickle crisis:
Abdominal manifestations
Mesenteric ischaemia
Cholelithiasis
Splenic infarct - wedge shaped infiltrate - conservative management
Splenic sequestration - Acute LUQ pain, splenomegaly, drop of >20 Hb
Other complications:
Stroke
Lung infarct
Obstructive sleep apnoea due to adenotonsillar hypertrophy - from compensatory asplenia and chronic infection
Priapism
Avascular necrosis of hip + shoulder, bone pain
Renal papillary necrosis
Renal medullary carcinoma
Rhabdomyolysis
Management
Sickle cell trait: Adequate hydration, avoid extremes of temperature and hypoxia
With abdominal pain, give IV fluids and oxygen 97% of crises should resolve in 48 hours. If it does not, consider surgical pathology
Pre-operative simple transfusion is as effective as exchange transfusions
Hydroxyurea - increases HbF, prevents sickling through multiple mechanisms
Splenic infarct - wedge shaped infiltrate - conservative management
Splenic sequestration - conservative, transfuse, or splenectomy - unclear which is optimal
Splenic abscess - percutaneous aspiration. Splenectomy if not possible
Hereditary Spherocytosis
Defect in red blood cell membrane proteins
In Europeans - combined Spectrin and Ankyrin deficiency
75% autosomal dominant
25% recessive forms and de novo mutations
Isolated beta-spectrin defects 15-30% - mild or moderate - autosomal dominant and do not require transfusion
Isolated alpha-spectrin defects 5% - usually severe, autosomal recessive
30% mild disease
70% moderate to severe
Neonates may drop Hb in first few weeks of life
Jaundice, haemolytic anaemia, splenomegaly
British Society for Haematology guidelines:
Grading Mild, Moderate, Severe
Based on Hb, Reticulocytes, Spectrin count, Bilirubin
Direct antiglobulin test to differentiate from autoimmune causes
Blood film - spherocytes
Management
Folate supplementation
Mild - Do not perform splenectomy in childhood
Moderate - Consider splenectomy based on symptoms
Severe - Perform splenectomy in childhood
Splenectomy around age 7, if either symptomatic, or before spleen too large - Splenectomy usually curative of anaemia and hyperbilirubinaemia
Cholecystectomy if symptomatic gallstones
Unclear evidence for benefit of cholecystectomy in asymptomatic gallstones, however cholecystectomy in childhood is risk of colonic cancer in later life
If doing partial splenectomy - can take 70-90% to preserve immune function
Can be complicated by parvovirus infection
Page edited by Mrs Charnjit Seehra BSc November 2024
References
Holcomb and Ashcraft’s Pediatric Surgery, 7th edition, 2020, Chapter 5
https://patient.info/doctor/sickle-cell-disease-and-sickle-cell-anaemia-pro
https://patient.info/doctor/thalassaemia-pro