Therapy Analysis - Sickle cell anaemia
Carrier or sufferer?
This hereditary disease is due to a single amino acid substitution of glutamic acid by valine on the ß-globin gene. Sickle-cell anaemia is autosomally recessive, meaning two copies of the defective gene must be present in the genome for the disease to take hold. If only one defective ß-globin gene is present, the dominant healthy gene overcomes protein production, and the offspring will only be a carrier of the sickle-cell trait. The condition is passed on to the offspring through the hereditary movement of the defective gene, which, if received from both mother and father, will make the offspring a sufferer. If one parent has sickle-cell anaemia and the other is normal, all of the children will be carriers. If one parent has the disease and the other has the trait, there is a 50% chance of having the disease or trait. When both parents have the trait, there is a 25% chance of having the disease and a 50% chance of having the trait (figure 1).
The disease materializes when two wild-type a-globin subunits and two mutant ß-globin subunits become associated to form HbS (the abnormal type of Hb), which polymerizes under low oxygen concentrations, distorting the shape of RBCs and causing them to lose their elasticity and thus have difficulty passing through capillaries.
Obstruction of the capillaries caused by sickle-shaped
RBCs can restrict blood flow to organs and therefore
reduce the amount of oxygen transported downstream
to tissue, resulting in ischaemic pain and organ damage
termed "vasoocclusive crisis" (VOC). The severity of
symptoms varies from person to person. Some people
have mild symptoms, while others are frequently
hospitalized for more serious complications.
The spleen
is frequently affected due its narrow vessels and its
function in clearing defective RBCs. This may lead to
lowered serum immunoglobulin levels and subsequent
decreased immunity, which in turn increases the risk of
infections such as pneumonia, influenza and meningitis.
Patients are often recommended for preventative
antibiotic and vaccination treatments. Painful
enlargements of the spleen (spleenic sequestration
crises) may require blood transfusions.
Aplastic crisis in sickle-cell patients causes baseline anaemia to be worsened because the production of RBCs is prevented for 2-3 days, leading to a further drop in Hb levels. Aplastic crisis is often a consequence of human parovirus B19 infection which affects erythropoiesis.This will result in tachychardia and fatigue. Other complications of sickle-cell anaemia include infection of the gallstones resulting from excessive bilirubin production due to prolonged haemolysis, as well as acute papillary necrosis of the kidney, leg ulcers, eye damage and pregnancy complications.
