Sickle Cell Disease

Question 1

Recall the prevalence of SCA in the UK?

Answer 1

Most prevalent monogenic disorder in UK

Question 2

What is genotype that produces full SCA?

Answer 2

HbS HbS

Question 3

Recall two compound heterozygous states of sickle cell disease

Answer 3

1. SC (C is another structural variant of HbC)

2. S-beta-thalassaemia = HbS and beta thalassaemia

Question 4

Recall the variance of symptoms in sickle cell anaemia

Answer 4

Even those with same genotype can be clinically heterogenous

Question 5

What does the term “sickle cell disease” refer to?

Answer 5

Any disease state that results from sickling

Question 6

Recall the 2 pathogenesis pathways that lead to anaemia in sickle cell disease

Answer 6

1. Shortened red-cell lifespan –> haemolysis

2. Reduced erythropoietic drive due to HbS having a low O2 affinity

Question 7

What is the difference between HbA and HbS?

Answer 7

Glutamic acid replaced by a valine at position 6

Question 8

Other than anaemia, what 2 pathologies are often seen in sickle cell disease as a direct result of shortened red cell lifespan?

Answer 8

Gall stones

Aplastic crisis

Question 9

What is an aplastic crisis and what is its most likely cause?

Answer 9

Temporary cessation of erythropoiesis

Parvovirus B19

Question 10

What are the 3 categories of pathology seen in sickle cell disease?

Answer 10

Haemolysis
Blockage to microvascular circulation
Limited NO availability

Question 11

What are the 3 main effects of microvascular circulation being blocked in sickle cell disease, and what are the subsequent effects of these?

Answer 11

Pain, dysfuction adn tissue necrosis

Necrosis –> bone disorders, skin ulceration and hyposplenism (due to repeated vaso-occlusive damage)

Question 12

What is the main effect of NO availability being limited in sickle cell disease? What causes availability to be low?

Answer 12

Pulmonary hypertension

Low due to NO being free in plasma following haemolysis

Question 13

When do symptoms of sickle cell disease first present and why?

Answer 13

Around 6 months when transition is made between HbF and HbA

Question 14

What are the 3 primary early manifestations of sickle cell disease?

Answer 14

Dactylitis
Splenic sequestration
Infection

Question 15

What is splenic sequestration?

Answer 15

Sudden acute pooling of blood in spleen

Question 16

What sort of infection is commonly seen in early sickle cell disease and why?

Answer 16

Pneumococcal - this is an encapsulated bacteria and so more likely to occue in SCD as there is hyposplenism

Question 17

Recall 3 later-stage manifestations of sickle cell disease (pre-crisis)

Answer 17

Stroke
Gall stones
The acute chest syndrome

Question 18

Why is the risk of gallstones increased in sickle cell disease?

Answer 18

Co-inheritance of Gilbert syndrome

Question 19

What is the acute chest syndrome?

Answer 19

Vaso-occlusive crisis of pulmonary vasculature

Question 20

Recall 4 symptoms of sickle cell emergencies

Answer 20

Septic shock
Cerebral haemorrhage
Hypoxia
Priapism

Question 21

Recall the 2 main consequences sickling of red cells

Answer 21

Dehydration of cells

Increased adherence to vascular endothelium

Question 22

What is the main feature of sickle cell disease shown by an FBC

Answer 22

High reticulocytes

Question 23

What 4 structures can be identified on a blood film that is positive for sickle cell disease

Answer 23

Sickled cells (obviously)
Boat cells
Target cells
Howell-Jolly bodies

Question 24

What is the first test done in suspected sickle cell disease and how does it work?

Answer 24

Solubility test: in the presence of a reducing agent ocyHb –> Hb causing solubility to decrease and solution to become turgid

Question 25

What method is used to definitively diagnose sickle cell disease?

Answer 25

HPLC

Question 26

Recall 2 preventative measures used in sickle cell disease?

Answer 26

Prophylactic penicillin for encapsulated bacteria infection risk
Train parents to examine abdomen for splenomegaly

Question 27

What supplement is given in sickle cell disease, and why?

Answer 27

Folic acid

Supplies folate for haematopoiesis

Question 28

Name and explain the mechanism of action of a drug used to treat sickle cell disease

Answer 28

Hydroxyurea: introduces HbF into blood to prevent sickling