Sickle cell disease

Question 1

What are the clinical features of sickle cell anaemia?

Answer 1

Clinically heterogenous

Early:

• Dactylitis
• Splenic sequestration
• Infection - S. pneumoniae
• Growth retardation
• Delayed puberty
• Low weight

Haemolysis:

• Anaemia
• Increased risk of gall stones
• Aplastic crisis (Parvovirus B19)

Blockage to microvascular circulation (vaso-occlusive crisis):

• Tissue damage and necrosis (infarction)
• Pain
• Dysfunction

Pulmonary hypertension

Question 2

What are the haematological features of SCD?

Answer 2

Low Hb (6-8g/dl)
High reticulocytes (except in aplastic crisis

Film:
Sickled cells
Boat cells
Target cells
Howell-Jolly bodies

Question 3

How is SCD generally managed?

Answer 3

Folic acid
Penicillin
Vaccination
Monitor spleen size
Blood transfusion for acute anaemic events, chest syndrome and stroke
Pregnancy care

Question 4

What conditions are included in SCD?

Answer 4

Sickle cell anaemia (HbSS)
Sickle cell trait (HbAS)
Sickle B-thalassaemia
HbSC disease

Question 5

Explain the genetic basis of SCD

Answer 5

Autosomal recessive

Single missense mutation at codon 6 of b globin gene

Question 6

Explain the pathophysiology of SCD

Answer 6

1. Glutamic acid (polar, soluble) replaced by valine (non-polar, insoluble)
2. Deoxyhaemoglobin S is insoluble
3. HbS polymerises to form fibres - “tactoids”
4. Intertetrameric contacts stabilise structure
5. Shortened red cell lifespan - haemolysis

Question 7

What are the stages of red cell sickling?

Answer 7

1. Distortion:
   Polymerisation initially reversible with formation of oxyHbS
   Subsequently irreversible
2. Dehydration
3. Increased adherence to vascular endothelium - get stuck in small post-capillary venules

Question 8

What are the consequences of tissue infarction in SCD?

Answer 8

Hyposplenism
Dactylitis
Avascular necrosis
Osteomyelitis
Chronic/recurrent leg ulcers

Question 9

How are painful SC crises managed?

Answer 9

Pain relief - opioids
Hydration
Keep warm
Oxygen if hypoxic
Exclude infection: blood and urine cultures, CXR
Exchange transfusion - lifesaving in stroke and acute chest syndrome
Haematopoietic stem cell transplantation (<16yr w/severe disease)
Induction of HbF

Question 10

How can hydroxyurea be used in SCD treatment?

Answer 10

Hydroxyurea induces HbF production
HbF inhibits polymerisation of HbS
Patients with higher HbF levels have fewer complications and improved survival

Question 11

What are the clinical features of sickle cell trait?

Answer 11

HbAS
Normal life expectancy
Normal blood count
Usually asymptomatic
Rarely painless haematuria
Caution: anaesthetic, high altitude, extreme exertion

Question 12

How is SCD diagnosed?

Answer 12

Solubility test:
In presence of reducing agent, oxyHb –> deoxyHb
Solubility decreases
HbS - solution becomes turbid

Definitive:
Electrophoresis
HPLC separates proteins according to charge

Question 13

What is the limitation of the solubility test in diagnosing SCD?

Answer 13

Doesn’t differentiate between AS and SS (trait and anaemia)

Question 14

What are some complications of SCD?

Answer 14

Lungs:
Acute chest syndrome
Chronic damage
Pulmonary hypertension

Urinary tract:
Haematuria (papillary necrosis)
Hyposthenuria (impaired conc of urine)
Renal failure
Priapism (prolonged erection)

Brain:
Stroke
Cognitive impairment

Eyes:
Proliferative retinopathy

Question 15

How does SCD present?

Answer 15

Symptoms rare before 3-6 months
Dactylitis (can lead to stubbing)
Splenic sequestration
Infection - S. pneumoniae

Question 16

Why does SCD rarely present before 3-6 months?

Answer 16

Onset coincides with switch from foetal to adult Hb synthesis (gamma globin to b globin)