W2 LECT 4: Sickle cell disease

Question 1

Sickle cell disease

Answer 1

• Is a B chain varient
• Results from a point mutation in position 6 of a Beta chain where Glutamic acid (CAG) is replaced by valine (CTG)
• The mutated B globin chain is then referred to as HbS

Question 2

List the Precipitants of sickling

• factors or conditions that can trigger the sickling of red blood cells (RBCs) in individuals with sickle cell disease (SCD)

Answer 2

↓ O2 tension
 ↓ pH
 Infection
 Cold
 Dehydration
 Injury/surgical trauma

Question 3

Name the 2 divisions of pathophysiology of the sickle cell disease

Answer 3

• Vaso-occlusion (major problem): blockage or occlusion of blood vessels by abnormally shaped red blood cells.
• Haemolysis (mostly IVH)

Question 3

Describe the impacts of vaso-occlusive episodes

Answer 3

• acute episode- cause sever pain
• repeated episode cause organ damage»organ dysfunction

Question 4

What are the clinical presentations of Sickle Cell Disease?

Answer 4

1. Anaemia (Haemolysis: IVH > EVH)
2. Crises:

Crises in sickle cell disease
1. Infarctive crisis
Sickle crisis is the hallmark of the disease. Infarction can occur in any organ or tissue but occurs commonly in bones, the chest or abdomen. Patients experience severe pain at the site of infarction. Blockage of cerebral vessels with cerebral infarction
leads to development of stroke.
2. Haemolytic crisis:
Catastrophic declines of haemoglobin can result from
i. Acute malaria.
ii. Acute haemolytic episodes in G6PD deficient subjects.
3. Aplastic crisis
This is most commonly caused by parvovirus B19 which infects and destroys red cell
precursors
4. Splenic sequestration crisis:
In this instance the spleen enlarges rapidly, often within hours, causing rapid pooling
of red cells in the spleen. This results in a sudden drop in the Hb which can be life
threatening. The mechanism is not known but pre-existing splenomegaly constitutes
a risk factor. Patients should be transfused urgently as a life saving measure. Rarely,
an urgent splenectomy may be necessary. More than one life threatening episode is
an indication for elective splenectomy.

3. Chronic organ damage (from infarction)

Question 5

Name the vaso-occlusive crisis

Answer 5

• Pain at site of ischaemia
  musculo-skeletal: long bones, joints, dactylitis ( “sausage digit,” refers to the painful swelling of the fingers and/or toes)*
  abdominal viscera → can mimic acute abdomen
  lungs → acute chest syndrome

Brain
Internal capsule → stroke
Frontal cortex → impaired cognition (silent
infarct)

Question 6

Chronic organ damage seen with SCD

Answer 6

Bone
Avascular necrosis- hip
Long bone fractures
Osteomyelitis- usu staph, salmonella, serratia

 Lungs
Pulmonary HT
Restrictive

 Spleen
Hyposplenism (due to progressive splenic damage)- which increases risk of infections

Renal
Tub damage- hyposthenuria (enuresis in children -bedwetting)
Glomerular damage  ESRD (median survival 2 years)

 CNS
CVA, cognition
 Substrate deficiency
 Fe / folate deficiency
(Frequent T/F  Fe overload)
 Leg ulcers

Question 7

Name various ways or procedures to Diagnose SCD

Answer 7

• Clinical presentation
   Peripheral blood smear
   Slide sickle test
  Drop of blood incubated with reducing agent →
  induces sickling
   Hb separation studies
  Hb electrophoresis
  HPLC

Question 8

Treatment- acute sickle crisis

Answer 8

Treatment- acute sickle crisis
 Pain relief
 Re-hydration
 Warmth
 Antibiotics if infection
 T/F if symptomatic anaemia
 (Steady state Hb: ~ 7-8 g/dl)

Question 9

For Long term management of SCD

Answer 9

• Preventive measures:
  Hydroxyuria: Induces HbF production
  50% ↓ion acute crisis, limits organ damage
  Infection: Immunisations, prophylactic penicillin
  Lifestyle change: maintain hydration, keep warm, avoid
  strenuous sports activity

 Substrate replacement: Folate/Fe
 Zn supplementation
 Newer therapies: attenuate severity  high cost

Question 10

Treatment of complications / organ damage from SCD

Answer 10

• Gall stones
  Cholecystectomy

 Avascular necrosis (AVN) hip
hip replacement

 Renal failure
dialysis
-Renal transplant

 Cardiac failure (Chronic anaemia)
Anti-failure treatment

 Hyposplenism
Prophylactic penicillin
Immunisation (encapsulated organisms)

 Pulmonary Hyper Tension
pulmonary vasodilators

Question 11

CURE for SCD

Answer 11

 Bone marrow transplantation;

Limitations
Compatible sibling
Mortality & morbidity (4%)
Expensive

 Gene therapy: Awaiting larger clinical trials

Question 12

What are the characteristics of Heterozygous sickle cell disease?

Answer 12

• Partial protection against malaria
   Generally asymptomatic - undiagnosed
   Hyposthenuria → enuresis
   Avoid excessive exertion

Question 13

What are the hereditary spherocytosis lab findings?

Answer 13

 FBC -pancytopaenia

Question 14

When is HbF replaced by HbS?

Answer 14

6 months after birth, when HbF subsides

Question 15

Clinical features of sickle cell disease

Answer 15

• Sickle cell crisis (pain from blockage of microvasculature): Patients are generally pale and may be jaundiced during a sickle crisis
• The spleen is enlarged in early childhood, but shrinks to a fibrotic mass due to repeated
  infarction.
• Height and weight are below average throughout childhood ( loss of height is in part due to
  damage to the spinal column from repeated infarction)
• Arms and legs are thin and long in comparison to body length
• The bones of the skull and face show ‘bossing’ as a result
  of bone marrow expansion.
• Onset of puberty is often delayed but fertility is usually not affected.