Clinical sesh - sickle cell 09/20 Faller

Question 1

why does sickle cell anema present around 6-7 months of age

Answer 1

by this time, most γHb has been eliminated from blood and the mutated βs protein is prevalent and causing problems

Question 2

rapid heart rate, rapid breathing, enlarged spleen, dactylitis, pale fingernails in a previously asymptomatic 6-month-old baby is suspicious of what protein misfolding disease?

Answer 2

sickle cell

• elevated HR/breathing to deliver O2 better
• enlarged spleen overworked breaking down sickled RBCs
• dactylitis = hand/foot syndrome = swollen fingers / toes, possibly due to vaso occlusion from sickled blockages
• pale fingernails = sign of anemia (low Hb, low hematocrit)

Question 3

hypoxia, stasis (slowing of blood flow), acidosis, increased 2,3-DPG, are pathophysiological signs of what protein misfolding disease?

Answer 3

sickle cell
-hypoxia = decreased O2 availability
-stasis = increased O2 extraction in tissues
-acidosis = loss of Hb buffering, infarction
-2,3-DPG to try to unload more O2
(vicious cycle)

Question 4

what is the HbS mutation?

Answer 4

Glu6Val mutation in β-Hb – allows aggregation through Val fit into hydrophobic pocket of another Hb molecule

Question 5

why are sickle cell patients susceptible to infection?

Answer 5

loss of spleen - infarcts from lack of blood

spleen functions as a large lymph node filtering blood, no spleen = risk of infection

Question 6

describe a molecular-based treatment (not just pain control or transfusions) for HbS patients

Answer 6

α-amino butyric acid can prevent switching off of γ-Hb, which allows continued production of HbF, which, in ratios >20% can ameliorate most complications of HbS by delivering O2 and preventing sickling

Question 7

why is α-amino butyric acid a successful therapy for sickle cell?

Answer 7

it can prevent switching off of γ-Hb, which allows continued production of HbF, which, in ratios >20% can ameliorate most complications of HbS by delivering O2 and preventing sickling