Sickle cell Flashcards
Genetics of SCD
Point mutation in beta-globin gene- valine (no charge) substituted for glutamic acid (negatively charged) at the 6th amino acid.
This mutation forms HbS, when forms parallel aggregates when deoxygenated- forms ‘sickly’ looking rbc.
This mutation is inherited in an autosomal recessive fashion.
Physiological effects of sickled red cells
The cells have an increased mechanical fragility, thus shorter lifespan: 6-10 days.
Rigid sickle cells make the blood more viscous, which can occlude small blood vessels.
Sickle cells also stick to the endothelium.
Epidemiology of SCD
The disease is distributed mainly across the Afro-Caribbean population.
Also mainly present in: India, Middle East, North Africa
Distribution of the condition correlates with incidence of Plasmodium falciparum- the sickle cell carriers have a selective advantage against the infection.
Oxygen dissociation curve for SCD
Due to low Hb, this is compensated by an increase in 2,3-DPG.
This stabilises R state further.
The dissociation curve shifts to the right, having even less affinity to O2, thus oxyhaemoglobin releases its O2 to tissues at higher PO2 levels.
Clinical features of SCD
Presents usually during infancy.
Anaemia
Jaundiced
Dactylitis
Splenic sequestration in children
Vaso-occlusive crisis
Pneumococcal septicaemia.
Dactylitis
Inflammation of of an entire finger or toes.
A clinical presentation of sickle cell anaemia.
If the epiphyseal plate is damaged, it can shorten the digit.
Chest syndrome
A clinical feature of sickle cell anaemia:
Dyspnoea
Pleuritic chest pain
Patchy shadowing on the CXR
Progressive hypoxia and fever.
Brain syndrome
A clinical feature of sickle cell which presents as stroke.
Aplastic crisis
A clinical feature of sickle cell.
It is a temporary cessation of RBC production.
When a SC person is infected with a parvovirus, this crisis occurs.
This causes severe anaemia.
Blood film for SCD
Sickle cells- spindle/boat shape.
Polychromasia: an abnormally high number of immature rbc (usually reticulocytes).
Howell-Jolly bodies: red blood cells with nuclear remnants- they are being pushed out of the cells prematurely
Sickle solubility test
Diagnosis for SCD:
Sodium dithionite is added to blood and will make RBC lyse and release Hb.
RBC with HbA will dissolve easily and form clear, red plasma.
RBC with HbS, will not dissolve as easily, The plasma will be cloudy due to the formation of crystals.
RBC with HbS and HbA (sickle cell trait), will have some clouding but not full blown like HbS.
Haemoglobin analysis
Diagnostic test used for SCD:
Hb electrophoresis-
Different Hb types have different charges. Electrophoresis separates the different Hb according to their charge.
Hb HPLC:
High performance liquid chromatography.
It analyses the types of Hb according to chemical properties- like gas chromatography.
Management of SCD
Antenatal screening
Prophylaxis against infections: penicillin, vaccinates
Prevention of crises.
Prevention of stroke in SCD
Transcranial doppler
If the blood flow is >200 cm/sec, this shows that the risk of stroke is significantly increased.
Stroke risk is reduced by exchange transfusion or hydroxyurea.
Management of crisis in SCD
Exclude any underlying infection.
Administer IV fluids.
O2 and analgesia
Antibiotics
FBC and reticulocyte count.
