Haemoglobinopathies Flashcards
Normal haemoglobin structure
4 globins and a haeme group
Globin chain genetics
4 alpha globin genes (2/parent)
2 beta globin genes (1/parent)
3 types of haemoglobin and their globin pairs
2 alpha + 2 beta = HbA
2 alpha + 2 delta = HbA2
2 alpha + 2 gamma = HbF
What mutation causes sickle cell disease
Autosomal recessive
Glutamine to Valine switching at codon 6 of beta globin chain
Sickle cell pathophysiology
First presents around 6 months (lower HbF)
Hypoxia → decreased oxygen tension → HbS polymerisation → sickling
Sickle cells fragile → haemolysis
Adherence to endothelium → accumulation of sickle cells in vessels → blockage of small blood vessels
Important features of sickle cell disease
How does age of onset affect presentation of sickle cell disease
Sickle Cell disease Dx
Blood film - sickle cells, target cells
Hb electrophoresis
Sickle cell disease Mx
Acute - opioids, blood transfusion
Chronic - PenV, pneumovax, HIB vax, folic acid, hydroxycarbamide, blood transfusions, carotid doppler monitoring, crizanlizumab, voxelotor
Thalassaemias pathophysiology
Unbalanced Hb synthesis → unmatched globins precipitate → haemolysis and ineffective erythropoiesis
Genetic pathophysiology of Beta thalassaemia
point mutations → decreased beta-chain sunthesis & excess alpha-chains
Features of beta thalassaemia
Increased HbA and HbF
Craniofacial changes
Hepatosplenomegaly
Explain the phenotypic variability of beta thalassaemia
Varying severity - major, intermedia and minor
Diagnosis of beta thalassaemia
Hb electrophoresis
Beta thalassaemia Mx
May not need treatment
Blood transfusion with iron chelation (desferrioxamine)
Regular screening for iron overload
Genetic pathophysiology of alpha thalassaemia
Deletions → reduced alpha chain synthesis and excess beta chains
Severity of alpha thalassaemia
4 alpha genes
1/2 deleted - asymptomatic, mild anaemia
3 deleted - HbH disease
4 deleted - Haemoglobin Bart’s Hydrops Foetalis - incompatible with life and death in utero
