Sickle Cell Disease Flashcards
Recall the prevalence of SCA in the UK?
Most prevalent monogenic disorder in UK
What is genotype that produces full SCA?
HbS HbS
Recall two compound heterozygous states of sickle cell disease
- SC (C is another structural variant of HbC)
2. S-beta-thalassaemia = HbS and beta thalassaemia
Recall the variance of symptoms in sickle cell anaemia
Even those with same genotype can be clinically heterogenous
What does the term “sickle cell disease” refer to?
Any disease state that results from sickling
Recall the 2 pathogenesis pathways that lead to anaemia in sickle cell disease
- Shortened red-cell lifespan –> haemolysis
2. Reduced erythropoietic drive due to HbS having a low O2 affinity
What is the difference between HbA and HbS?
Glutamic acid replaced by a valine at position 6
Other than anaemia, what 2 pathologies are often seen in sickle cell disease as a direct result of shortened red cell lifespan?
Gall stones
Aplastic crisis
What is an aplastic crisis and what is its most likely cause?
Temporary cessation of erythropoiesis
Parvovirus B19
What are the 3 categories of pathology seen in sickle cell disease?
Haemolysis
Blockage to microvascular circulation
Limited NO availability
What are the 3 main effects of microvascular circulation being blocked in sickle cell disease, and what are the subsequent effects of these?
Pain, dysfuction adn tissue necrosis
Necrosis –> bone disorders, skin ulceration and hyposplenism (due to repeated vaso-occlusive damage)
What is the main effect of NO availability being limited in sickle cell disease? What causes availability to be low?
Pulmonary hypertension
Low due to NO being free in plasma following haemolysis
When do symptoms of sickle cell disease first present and why?
Around 6 months when transition is made between HbF and HbA
What are the 3 primary early manifestations of sickle cell disease?
Dactylitis
Splenic sequestration
Infection
What is splenic sequestration?
Sudden acute pooling of blood in spleen
What sort of infection is commonly seen in early sickle cell disease and why?
Pneumococcal - this is an encapsulated bacteria and so more likely to occue in SCD as there is hyposplenism
Recall 3 later-stage manifestations of sickle cell disease (pre-crisis)
Stroke
Gall stones
The acute chest syndrome
Why is the risk of gallstones increased in sickle cell disease?
Co-inheritance of Gilbert syndrome
What is the acute chest syndrome?
Vaso-occlusive crisis of pulmonary vasculature
Recall 4 symptoms of sickle cell emergencies
Septic shock
Cerebral haemorrhage
Hypoxia
Priapism
Recall the 2 main consequences sickling of red cells
Dehydration of cells
Increased adherence to vascular endothelium
What is the main feature of sickle cell disease shown by an FBC
High reticulocytes
What 4 structures can be identified on a blood film that is positive for sickle cell disease
Sickled cells (obviously)
Boat cells
Target cells
Howell-Jolly bodies
What is the first test done in suspected sickle cell disease and how does it work?
Solubility test: in the presence of a reducing agent ocyHb –> Hb causing solubility to decrease and solution to become turgid
What method is used to definitively diagnose sickle cell disease?
HPLC
Recall 2 preventative measures used in sickle cell disease?
Prophylactic penicillin for encapsulated bacteria infection risk
Train parents to examine abdomen for splenomegaly
What supplement is given in sickle cell disease, and why?
Folic acid
Supplies folate for haematopoiesis
Name and explain the mechanism of action of a drug used to treat sickle cell disease
Hydroxyurea: introduces HbF into blood to prevent sickling
