Haematology (sickle cell) Flashcards
What is sickle cell disease?
commonest genetic disorder in children. 1 in 2000
HbS is inherited- HbS forms as a result of a point mutation in codon 6 of the β-globin gene, which causes a change in the amino acid encoded from glutamine to valine
More common in afro-caribbean, African, Middle East
What are the 3 main forms of sickle cell disease?
o Sickle cell anaemia (HbSS): patients are homozygous for HbS, they have small amounts of HbF and no HbA because they have the sickle mutation in both β-globin genes.
o HbSC disease (HbSC)- affected children inherit HbS from one parent and HbC from the other parent, so they also have no HbA because they have no normal β-globin genes. HbC is formed as a result of a different point mutation in β-globin
o Sickle β-thalassaemia: affected children inherit HbS from one parent and β-thalassaemia trait from the other, they have no normal β-globin genes and most patients can make no HbA, therefore have similar symptoms to those with sickle cell anaemia
What is sickle trait?
inheritance of HbS from one parent and a normal β-globin gene from the other parent
Approximately 40% of the haemoglobin is HbS, they do not have sickle cell disease but are carriers of HbS, so can transmit HbS to their offspring, they are asymptomatic and are only identified as a result of blood tests
What occurs in sickle cell disease?
HbS polymerises within red blood cells forming rigid tubular spiral bodies which deform the red cells into a sickle shape
• Irreversibly sickled red cells have a reduced lifespan-trapped in the microcirculation, resulting in blood vessel occlusion (vaso-occlusion) and therefore ischaemia in an organ or bone. Exacerbated by low oxygen tension, dehydration and cold
What are the clinical manifestations in sickle cell disease?
Moderate anaemia (Hb 6-10) with jaundice from chronic haemolysis
Infection: increased susceptibility due to hyposplenism and micro infarction in the spleen. (His, pneumococci, osteomyeliti- salmonella)
Painful crises- hand-foot syndrome, dactylitis, swelling and pain of the fingers/feet. Bones of limbs and spine.
Priapism- treat with exchange transfusion, lead to erectile impotence
Splenomegaly
What occurs in painful crises in sickle cell?
Vaso-occlusive crises causing pain
Actute chest syndrome- severe hypoxia and need for mechanical ventilation and emergency transfusion
Avascular necrosis of femoral heads
Crises may be precipitated by exposure to cold, dehydration, excessive exercise or stress, hypoxia or infection
What causes acute anaemia in sickle cell?
Haemolytic crises- associated with infection
Aplastic crises- parvovirus infection- cessation of blood cell production
Sequestration crises- sudden splenic or hepatic enlargement, abdominal pain and circulatory collapse from accumulation of sickled cell in spleen
What are the long term problems in sickle cell?
Short stature and delayed puberty
Stroke and cognitive problems
Adenotonsillar hypertrophy- sleep apnoea, vaso-occlusive crises
Cardiac enlargement- chronic anaemia
Heart failure
Renal dysfunction- may exacerbate enuresis
Pigment gallstones- increased bile pigment production
Leg ulcers
Psychosocial problems
What is the prophylaxis for sickle cell?
Vaccinations- pneumococcal, Haemophilus influenzae type B and meningococcus infection
Daily oral penicillin- coverage of all pneumococcal subgroups
Daily folic acid- increased demand caused by chronic haemolytic anaemia
Avoid exposure to cold, dehydration, excessive exercise, undue stress or hypoxia
What is the management for sickle cell disease?
Acute crises- oral or IV analgesia, good hydration, antibiotics, oxygen if sats low, exchange transfusion in acute chest syndrome, stroke and priapism
Chronic problems- hydroxyurea, drug which increases their HbF production and helps protect against further crises (monitor for WCC suppression)
Bone marrow transplant in severe cases- only if HLA-identical sibling who can donate their bone marrow- the cure rate is 90% but there is a 5% risk of fatal transplant-related complications
What is the prognosis of sickle cell disease?
• Around 50% of patients with the most severe form of sickle cell disease die before the age of 40 years-
however, the mortality rate during childhood is around 3%, usually from bacterial infection
What is the prenatal screening for sickle cell disease?
perform neonatal screening on dried blood spots (Guthrie test) collected in the first week of life
• Early diagnosis of sickle cell disease allows penicillin prophylaxis to be started in early infancy instead of awaiting clinical presentation- possibly due to a severe infection
• Prenatal diagnosis can be carried out by chorionic villus sampling at the end of the first trimester if parents wish to choose this option to prevent the birth of an affected child
