Haemoglobinopathy Flashcards
Describe the structure of haemoglobin
Tetramer made up of 2 alpha globin like chains and 2 beta globin like chains One haem group attached to each globin chain
What are the 3 major forms of Hb?
HbA (2 alpha and 2 beta chains), HbA2 (2 alpha and 2 delta chains) and HbF (2 alpha and 2 gamma chains)
Where are the alpha like genes found?
Chromosome 16 - 2 alpha genes per chromosome (4 per cell)
Where are the beta like genes found?
Chromosome 11 - one beta gene per chromosome (2 per cell)
What is a haemoglobinopathy?
A hereditary condition affecting globin chain synthesis
What are the 2 main groups of haemoglobinopathies?
Thalassaemias and structural haemoglobin variants
What is the difference between thalassaemias and structural haemoglobin variants?
Thalassaemia - decreased rate of globin chain synthesis resulting in impaired Hb production Structural haemoglobin variants - normal production of structurally abnormal globin chain -> variant Hb e.g. HbS
What happens as a result of thalassaemias?
Inadequate Hb production -> microcytic hypochromic anaemia. Unbalanced accumulation of globin chains is toxic -> ineffective erythropoiesis and haemolysis
Where are thalassaemias most common?
Parts of Africa, SE Europe, India and most of Asia
What is alpha thalassaemia?
Mutations affecting alpha globin chain synthesis. Results from deletion of one a+ or both a0 alpha genes from chromsome 16. Reduced a+ or absent a0 alpha chain synthesis. a chains present in all adult forms of Hb therefore HbA HbA2 and HbF all affected
How is alpha thalassaemia classified?
alpha thal trait - one or two genes missing HbH disease - only one alpha gene left Hb Barts hydrops fetalis - no functional alpha genes
How does alpha thalassaemia trait present and how is it managed?
Asymptomatic, no treatment needed.
Describe the red cell appearance in alpha thalassaemia trait
Microcytic, hypochromic red cells with mild anaemia
What is the pathophysiology of HbH disease?
Severe form of alpha thalassaemia. Only one alpha gene per cell. Anaemia with very low MCV and MCH. Excess beta chains form tetramers called HbH which can’t carry oxygen. Red cell inclusions of HbH can be seen with special stains
Where is HbH disease most common and what are the clinical features?
Most common in SE Asia, Middle East and Mediterranean where a0 is prevalent. Features - moderate anaemia, splenomegaly, jaundice, growth retardation, gallstones and iron overload
What is Hb Barts hydrops foetalis syndrome?
Severest form of alpha thalassaemia. No alpha genes inherited from either parent. Minimal or no alpha chain production -> HbA can’t be made! Hb Barts and HbH are the majority of Hb present at birth
What are the clinical features of Hb Barts hydrops fetalis syndrome?
Severe anaemia, cardiac failure, growth retardation, severe hepatosplenomegaly, skeletal and cardiovascular abnormalities, almost all die in utero
What is beta thalassaemia?
Disorder of beta chain synthesis. Only have beta chains and hence only HbA affected
What causes beta thalassaemia?
Usually point mutations. Reduced or absent beta chain production depending on the mutation.
How is beta thalassaemia classified?
Based on clinical severity: - beta thalassaemia trait - asymptomatic - beta thalassaemia intermedia - moderate severity, occasional transfusions - beta thalassaemia major - severe, lifelong transfusions
How does beta thalassaemia major present?
Presents aged 6-24 months, as HbF falls, with pallor and failure to thrive
What does beta thalassaemia major cause?
Extramedullary haematopoiesis which causes hepatosplenomegaly, skeletal changes, organ damage, cord compression
How is beta thal major treated?
Regular transfusions to maintain Hb at 95-105g/L Bone marrow transplant may be an option if done before complications develop
What is the main cause of mortality in beta thal major?
Iron overload! (>70% of deaths are due to iron)
