Expansion
A single amino acid substitution causes polymerisation of deoxygenated haemoglobin
Expansion
A glutamate to valine substitution at position 6 of the beta chain produces HbS. When deoxygenated, HbS polymerises, distorting the cell into a sickle shape.
Consequences:
- Vaso-occlusion: rigid cells obstruct the microcirculation, causing painful crises, acute chest syndrome, stroke, priapism and avascular necrosis
- Haemolysis: the sickled cell has a lifespan of only 10 to 20 days
- Hyposplenism: repeated infarction causes autosplenectomy by early childhood, hence susceptibility to encapsulated organisms and the need for penicillin prophylaxis and vaccination
- Parvovirus B19 causes aplastic crisis by arresting erythropoiesis in a patient with no reserve
Precipitants: hypoxia, dehydration, cold, infection, acidosis, stress and pregnancy.
Timing: symptoms begin at 3 to 6 months, when HbF is replaced by HbS.
Hydroxycarbamide works by increasing HbF, which does not participate in polymerisation, and this is why it reduces crisis frequency.
Sickle trait is largely asymptomatic and confers protection against falciparum malaria, which explains its geographical distribution.