Haemoglobinopathies Flashcards
Structure of Hb + different forms
4 globin chains each with haem group
3 normal forms - HbA (A2B2), HbA2 (A2D2), HbF (A2G2) - all have 2 alpha
HbF in utero then A2 and A increase with HbA taking over at 3-6m
Hb genetics
4 copies of alpha globin gene (chromosome 16)
2 copies of beta, gamma and delta globin genes (chromosome 11)
Qualitative vs. quantitative defect in B-globin chain synthesis
Qualitative = Sickle cell anaemia Quantitative = Thalassaemia
Mutation in SCD
Point mutation GAG -> GTG
= Glu -> Val at 6th position in B-globin protein = Bs-globin protein
a) Asymptomatic unless hypoxic trigger BBs (HbA + HbS)
b) Sickling at rest + after hypoxic trigger BsBs (HbS only)
a) Sickle cell trait
b) Sickle cell anaemia
Pathophysiology of sickle cell anaemia
Bs aggregates Hb molecules together - RBCs elongate then sickle - destroyed by haemolysis (anaemia) + prone to get stuck in capillaries (vaso-occlusion + infarction)
Blood film features of SCD
Sickle cells
Howell-Joly bodies from hyposplenism
HbA
2 alpha, 2 beta
HbA2
2 alpha, 2 delta
HbF
2 alpha, 2 gamma
Reduced B-chain synthesis, excess alpha chains Point mutations Bony deformity (skull bossing, maxillary hypertrophy, hairs on end on skull X-ray)
B-thalassaemia
Spectrum of disease (minor, major, intermedia) depending on how many B-cahins are mutated
Pathophysiology thalassaemia
Reduced alpha / beta globin chain synthesis
Reduced synthesis of Hb involving that chain
Haemolysis of RBCs with unbalanced Hb + also reduced synthesis of RBCs
Asymptomatic carrier
May be mild anaemia
B-thalassaemia minor ‘trait’
1 B-globin chain mutated, 1 B-globin chain normal
Severe anaemia
HF - will die without transfusion
B-thalassaemia major
Both B-globin chains mutated
Decreased alpha chain synthesis, excess B-chains
Less of all Hb types
Point deletions
Alpha thalassaemia
