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