Haemoglobinopathy Flashcards
What causes HbS to form?
Missense mutation in the beta globin gene
Substitution of glutamic acid by valine
What happens to HbS at low oxygen levels?
Deoxy Hb polymerises into long intracellular fibres called tactoids
This conforms the RBC into an inflexible sickle chape which cannot flow easily through blood vessels
What is the solubility like of HbS?
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 in a sickle cell anaemia patient?
Reticulocytes
Target cells (with Howell-Jolly Bodies)
Sickle cells
What are Howell-Jolly Bodies (in target cells) and what are they caused by?
Clusters of DNA still present in circulating RBCs
Arises when patients have reduced splenic function
Why does sickle cell disease lead to splenic complications?
Sickling vaso-occlusion can occur in the microvasculature of the spleen
Repeated occlusions leads to destruction and splenic sequestration
Why does splenic sequestration occur 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 blood pooling in the spleen
Why might you find elevated gall stones in patients with SCD?
Increased haemolysis leads to increased bilirubin production and increased gall stone formation
Why might jaundice occur in patients with SCD?
More haemolysis of RBC thus more bilirubin
Leaves yellow tint to skin and sclera of eye
What is a common early manifestation of SCD?
Dactylitis which is inflammation of the digits
What is hyposplenism?
Reduced splenic function 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 HbF production which has higher O2 affinity
This reduces recurrent vaso-occlusive crises
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?
Chest X-ray shows new pulmonary infiltrate
With fever, cough, chest pain, tachypnoea
What other conditions can SCD cause?
Acute chest syndrome
Avascular necrosis of femoral head
Hyposplenism
Jaundice
Stroke
Osteomyelitis
How does the sickle solubility test work in diagnosing SCD?
In presence of reducing agent (sodium dithionite), oxyHb is converted to deoxyHb
HbA dissolves easily but HbS is insoluble and 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?
Electrophoresis or high performance liquid chromatography to separate proteins according to charge
