Haematology - Haemoglobinopathies Flashcards
How can you diagnose a haemoglobinopathy?
Through Hb electrophoresis
What is normal haemoglobin comprised of?
4 Globins arranged around a haem molecule in 2 pairs
- 4 α globin genes (2 from each parent)
- 2 β globin genes (1 from each parent)
What is the default Hb?
HbA - 95%
2 α + 2 β globins
What is HbA2 comprised of?
2 α + 2 delta globins
What is HbF comprised of?
2 α + 2 gamma globins
- Common in babies <6months
Which conditions affect the β globin genes?
- Sickle Cell disease
- β thalassaemia
Which conditions affect the α globin genes + how?
- α thalassaemia
- HbH disease
- mutations cause deletions of α globin genes
What is the mode of inheritance of Sickle Cell disease?
Autosomal recessive
What is the mutation in Sickle Cell disease?
- Single base mutation
- GAG –> GTG
- Glu –> Val at codon 6 of β chains
- Causes HbS instead of HbA
What type of haemoglobin is present in sickle cell anaemia?
HbSS
What type of haemoglobin is present in sickle cell trait?
HbAS
What is sickle-haemoglobin C disease?
- HbSC
- Where one HbS is inherited from one parent and one HbC (defective β chain) is inherited from another
- Milder than HbSS usually
What is sickle β thalassaemia?
- HbS/β
- HbS from one parent, β thalassaemia trait/β0 from the other
- Similar in severity to HbSS
At what age does sickle cell anaemia manifest and why?
At 3-6 months
- Coinciddes with decreasing HbF
What causes sickling
Decreased O2 tension leads to HbS polymerisation, thus causing sickling
What type of haemolysis is present in a sequestration crisis?
Extravascular
What features are present in haemolysis in a sickle cell patient?
- Anaemia 60-80g/L
- Splenomegaly
- Folate deficiency
- Gallstones
- Aplastic crisis (parvovirus B19)
What features are seen in vaso-occlusion/infarction in a sickle cell patient?
- Stroke
- Infections (hyposplenism, CKD)
- Crises (splenic, sequestration, chest + pain)
- Kidney (papillary necrosis, nephrotic)
- Liver (gallstones)
- Eyes (retinopathy)
- Dactilitis (impaired growth)
- Mesenteric ischaemia
- Priapism
What does salmonella cause in a sickle cell patient?
Osteomyelitis
What does strep. pneumoniae cause in a sickle cell patient?
Sepsis
What symptoms are seen in a sickle cell child?
- Strokes
- Splenomegaly + splenic crises
- Dactylitis
What symptoms are seen in a sick cell teenager?
- Impaired growth
- Gallstones
- Psych
- Priapism
What symptoms are seen in a sickle cell adult?
- Hyposplenism
- CKD
- Retinopathy
- Pulmonary hypertension
- Iron overload (from transfusions)
What is seen on a blood film of a sickle cell patient?
- Sickle cells
- Target cells
Whta does a sickle solubility test show?
It’s positive in HbSS + HbAS
What test is done at birth to identify sickle cell anaemia and what treatment is given?
- Guthrie test
- Pneumococcal prophylaxis
What is the treatment for acute sickle cell anaemia?
- Opioid analgesia (for painful crises)
- Blood transfusion (usually exchange transfusion in severe crises)
What is the treatment for chronic sickle cell anaemia?
- Penicillin V
- Pneumovax
- HIB vaccine
- Folic acid
- ?Hydroxycarbamide
- regular exchange transfusions
- carotid doppler monitoring in early childhood
- ?Hydroxyurea
- ?Crizanlizumab
- ?Voxelotor
How does thalassaemia affect the body?
Unbalanced Hb synthesis leads to unmatched globins precipitate which causes haemolysis and ineffective erythropoeisis
What is seen on a peripheral blood smear of a thalassaemic patient?
- Basophilic stippling
- Target cells
What is the pathophysiology of β thalassaemia?
Point mutations in Chr 11 leads to reduced β chain synthesis which causes excess α chains
What signs are seen in β thalassaemia?
- SKULL BOSSING
- MAXILLARY HYPERTROPHY
- HAIRS ON END SKULL X-RAY
- Hepatosplenomegaly
What are the different genotypes in β thalassaemia?
- B0 = no expression of gene
- B+ = some expression of the gene
- B = normal gene
What are the different genotypes for β thalassaemia minor?
- B/B0
- B/B+
- Heterozygous
What is seen in a patient with β thalassaemia minor?
- Asymptomatic (carrier)
- Mild anaemia
What are the different genotypes for β thalassaemia intermedia?
- B+/B+
- B+/B0
- moderate reduction in β globin chain production
What is seen in a patient with β thalassaemia intermedia?
- Moderate anaemia
- Splenomegaly
- Bony deformity
- Gallstones
What is the genotype for β thalassaemia major?
- B0/B0
- Homozygous
What is seen in a patient with β thalassaemia major?
- 3-6mnths severe anaemia
- FTT
- Hepatosplenomegaly (extramedullary erythropoeisis)
- Bony deformity
- Severe anaemia
- Heart failure
How is β thalassmia diagnosed?
- Guthrie test at birth
- Hb electrophoresis
- High performance liquid chromatography
What is the treatment for β thalassaemia?
- Minor + some intermedia don’t need regular Tx
- Blood transfusion with iron chelation (to prevent overload)
- Folic acid
- Regular screening for iron overload in heart + liver
What is the pathophysiology of α thalassaemia?
Deletions in Chr16 cause reduced α chain synthesis, resulting in excess β chains
What are the different types of α thalassaemia and how are they differentiated?
- α thalassaemia trait: 1/2 deletions
- HbH disease: 3 deletions
- Hydrops foetalis: 4 deletions
What is seen in a patient with α thalassaemia trait?
- Asymptomatic
- Mild anaemia
If 1 deletion = silent
If 2 deletions = trait
What is seen in a patient with HbH disease?
- Moderate anaemia
- Splenomegaly
What is seen in a patient with hydrops foetalis?
- Incompatible with life
(also known as HbBarts)
What is the management of a patient with α thalassaemia?
- Trait doesn’t need regular Tx
- Blood transfusion with iron chelation (to prevent overload)
- Folic acid
- Regular screening for iron overload in heart + liver
