Haemoglobinopathy Flashcards
What causes HbS to form?
A missense mutation in the beta globin gene which results in a valine substitution for glutamic acid
What happens to HbS at low oxygen levels?
The de-oxy Hb polymerises into long intracellular fibres = tactoids which conforms the RBS into a highly unflexible sickle shape, which are more sticky and therefore cannot flow through the blood vessels
What is the solubility like of HbS?
it is highly insoluble
Which condition does the distribution of the Sickle Cell gene match?
Plasmodium falciparum malaria
Where is HbS particularly prevalent?
In tropical Africa and some parts of the Miditerranean, Middle East and India
What is the phenotype of. person carrying two copies of the Beta sickle gene?
Sickle Cell Anaemia
What is the lifespan of a sickled red blood cell like compared with a normal one?
10-20 days, compared with the 120 normal days
Why might a patient with sickle cell anaemia have a high reticulocyte count?
The bone marrow compensates for the destruction of sickle cells by producing more red blood cells, hence an increase in immature RBCs
Which type of blood cells might specifically be seen on a blood film?
Reticulocytes, target cells (Howell-Jolly Bodies) and Sickle Cells
What are Howell-Jolly Bodies?
Cells with DNA still present in the center of the cell - arises when patients have reduced splenic function
Why does sickle cell disease lead to splenic complications?
The microvasculature of the spleen is a prime place for sickling vaso-occlusion to occur - repeated occlusions leads to destruction and engoregement of the spleen with blood (spleen sequestration)
Why is haemolysis increased in SCD?
The RBCs have a shorter life span (20 days), and therefore are destroyed more quickly - when the spleen cannot cope with this high load, it can lead to pooling in the spleen
Why might you find elevated gall stones in patients with SCD?
More bilirubin is produced as there is more haemolysis of the RBCs, which as a result leads to more gall stones forming
Why might jaundice occur in patients with SCD?
More haemolysis of RBC = more bilirubin forming, leaving yellow tint to the skin and sclera of the eye
What is a common early manifestation of SCD?
Dactylitis which is inflammation of the digits
What is hypopslenism?
When the spleen doesnt work any more due to repeated vaso-occlusion
What can hyposplenism lead to in terms of infection\?
Increased succeptibility to encapsulated bacterial infections
What are sickle cell crises?
Vaso-occlusive crises which are a hallmark of sickle cell diease
They are acute episodes of pain, usually felt in the lower back, pelvis and legs
Why are SCD patients given hydroxyurea?
Hydroxyurea stimulates the production of HbF which has a high affinity for Oxygen, and therefore reduce the recurrent episodes of vaso-occlusive crises which SCD patients may face
In patients heterozygous for the beta sickle gene, what is seen on gel electrophoresis?
Both HbA and HbS are seen
What is acute chest syndrome in SCD?
Vaso-occlusion of the pulmonary vasculature, which should be treated as a medical emergency
How is acute chest syndrome diagnosed?
New pulmonary infiltrate on chest X-ray
with Fever
Cough
Chest pain
Tachypnoea (rapid breathing)What other conditions can SCD cause?
Stroke, Hyposplenism, jaundice, Acute Chest Syndrome, Avascular necrosis of femoral head, Osteomyelitis
How does the sickle solubility test work in diagnosing SCD
In the presence of a reducing agent oxyHb converted to deoxy Hb
Solubility decreases
Solution becomes turbid
What is the problem with the sickle solubility test in the diagnosis of SCD?
Does not differentiate AS from SS
What does the definitive diagnosis of SCD require?
Definitive diagnosis requires Electrophoresis or High Performance Liquid Chromatography (HPLC) to separate proteins according to charge
