Sickle cell Anaemia

Question 1

what distinguishes HbA and HbS?

Answer 1

a single amino acid difference in beta-chain of Hb

Question 2

what is beta^S?

Answer 2

• point mutation at codon 6 of genes for beta globin
• glutamic acid is replaced by valine
• beta S insoluble
• HbS polymerises to form fibres called Tactoids
• inter-tetrameric contacts stabilise structure

Question 3

what are the stages in sickling of RBCs?

Answer 3

• distortion - polymersiation initially reversible with formation of oxyHbS but is then irreversible
• dehydration
• inc. adherence to vascular endothelium

Question 4

what is sickle cell disease?

Answer 4

sickle cell anaemia and all the other conditions that lead to a disease syndrome due to sickling of RBCs

Question 5

how does SCD affect the CVS?

Answer 5

• shortened red cell life span = haemolysis so get anaemia, gallstones, aplastic crisus
• blockage to microvascular circulation (infarction, pain and dysfunction)

Question 6

what does infarction cause in the spleen, bones/joints and skin?

Answer 6

• spleen: hyposplenism (leads to infarction)
• bones/joints: dactylitis (inflammation of bone), avascular necrosis and osteomyelitis (infection of bone)
• skin (ulcerations)

Question 7

how does SCD affect the lungs?

Answer 7

• acute: acute chest syndrome

- chronic: pulmonary hypertension

Question 8

how does it cause hypertenion?

Answer 8

• correlates with severity of haemolysis

- free plasma haemoglobin from haemolysis scavenges NO and causes vasoconstriction

Question 9

what is the effect of SCD on urinary tract?

Answer 9

• haematuria - due to papillary necrosis
• renal failure and hyposthenuria (impaired conc. of urine)
• priapism

Question 10

what are the effects of SCD on the brain?

Answer 10

stroke and cognitive impairment

Question 11

what are the effects of SCD on the eye?

Answer 11

proliferative retinopathy

Question 12

when is the clinical presentation seen?

Answer 12

• symptoms rare before 3-6 months

- as switch to adult HbA synthesis hasn’t occur yet

Question 13

what are the early manifestations?

Answer 13

• dactylitis (most common in children)
• splenic sequestration
• infection (mostly pneumoccocal)

Question 14

what can painful crises be triggered by?

Answer 14

• infection
• exertion
• dehydration
• hypoxia
• psychological stress

Question 15

what is the mortality of SCD?

Answer 15

• females = 48 years
• males = 42 years
• 21% from painful crises
• 14% from chest syndrome

Question 16

how do you generally manage it?

Answer 16

• folic acid (anaemia)
• penicillin (splenic dysfunction)
• vaccination (splenic dysfunction)
• monitor spleen size
• blood transfusion for acute anaemia, chest syndrome, stroke
• pregnancy care

Question 17

how do you manage painful crises?

Answer 17

• painful relief
• hydration
• keep warm
• oxygen if hypoxic

Question 18

when are haematopoietic stem cell transplantions used? what is the survival rate?

Answer 18

from sibling HLA or other haplo-identical donors
<16 years with SCD
survival rate = 90-95%
cure in 85-90%

Question 19

how can a chemotherapy agent reduce the occurence of SCD symptoms?

Answer 19

• hydroxyurea/ hydroxycarbimide
• induces expression of HbF
• up to 20% more HbF

Question 20

what are the lab features?

Answer 20

• Hb is low (6-8g/dL)

- reticulocytes high

Question 21

what would you see on the film?

Answer 21

• sickled cells
• boat cells
• target cells
• Howell-Jolly bodies

Question 22

what is the solubility test?

Answer 22

• in presence of reducing agent, oxyHb is converted to deoxyHb
• solubility dec. and solution becomes turgid
• doesn’t differentiate AS from SS though
• only checks to see if you have one or more sickle traits

Question 23

describe the features of the sickle cell trait

Answer 23

• normal life expectancy
• normal blood count
• usually asymptomatic
• caution taken with: anaesthetic, high altitude, extreme exertion