7. Sickle Cell Anaemia

Question 1

What is sickle cell anaemia?

Answer 1

Sickle cell anaemia,
or disease,

is a haemoglobinopathy with
autosomal recessive inheritance.

It occurs because of a point mutation on the gene
coding for

normal haemoglobin (HbA) on chromosome 11,

which causes the substitution of valine for glutamic acid at position 6 on the β-haemoglobin chain.

This results in the formation of an abnormal β-haemoglobin chain,
referred to as ‘HbS’.

Homozygotes (HbSS) have only abnormal haemoglobin.

Heterozygotes (HbAS) are said to have ‘sickle cell trait’,

and possess both abnormal and normal haemoglobin.

Question 2

Incidence

Answer 2

The trait is carried by 25% of West Africans,

10% of African Americans and also by those

of East Indian, Middle Eastern and
Mediterranean origin,

where selective pressures of malaria have driven its
inheritance.

Sickle cell trait is thought to confer some protection against falciparum malaria as the parasite normally completes part of its life cycle within red blood cells.

The lifespan of the red blood cells carrying HbS is
reduced, and this prevents the parasite from completing its life cycle.

Question 3

What do you understand by the term ‘sickling’?

Answer 3

At low partial pressures of

oxygen,

deoxygenated HbS polymerises,

becomes insoluble and
precipitates to form elongated crystals or ‘tactoids’

.
These cause the red blood cell to become
rigid and form a ‘sickle’ shape.

This process increases in the presence of

hypoxia,
acidosis,
dehydration and
hypothermia.

The degree of sickling is proportional to the concentration of the abnormal haemoglobin,
HbS, present in the blood.

Question 4

Homozygotes

PaO2 for sickling vs

Heterozygotes

What is the effect of sickling

What is the life span

What is the consequence of this lifespan

Answer 4

In homozygotes,

HbS polymerises at PaO2s between 5 and 6 kPa,

and so the red blood cells of these patients sickle continuously within the venous circulation.

In heterozygotes with only 20–45% of abnormal haemoglobin, sickling occurs at much lower PaO2 of 2–3 kPa.

Sickled blood cells increase blood viscosity, reduce flow and occlude smaller capillaries causing venous thrombosis and distal organ infarcts.

They have a reduced lifespan of 10–20 days, compared to the normal lifespan of 120 days.

Consequently, sickle cell disease sufferers are typically anaemic (haemolytic) and jaundiced. HbS shifts the oxyhaemoglobin dissociation
curve to the right.

Question 5

What are the complications associated with sickle cell

disease?

Answer 5

Patients with sickle cell trait are
usually asymptomatic under normal conditions.

Those with sickle cell disease can suffer multi-organ pathology associated with a life expectancy of 40–50 years.

Clinical features in those with sickle cell disease only appear from 6 months of age as adult
haemoglobin begins to replace fetal,

which has no β chains.

Homozygotes suffer periods where their disease is worse, called ‘sickle cell crises’.

Question 6

Sickle cell crises:

Answer 6

1
> Vaso-occlusive:
Sickled cells obstruct blood flow to an organ or tissue.

Most patients have infarcted their spleens by an early age and are on lifelong prophylactic penicillin.

Pain control is with simple analgesia and
opiates.

> Sequestration: Painful splenic enlargement results in anaemia and abdominal distension.
Management is supportive.

> Aplastic:
Usually triggered by infection with parvovirus B19, which arrests red cell production for 2–3 days.

Reticulocyte count and Hb fall acutely.

In normal individuals this is not clinically significant, but in sickle cell homozygotes who already have shortened red cell survival, it can result in life-threatening anaemia.

> Haemolytic:
The rate of red cell breakdown increases. This is rare and usually seen in only those with co-existing G6PD deficiency.

Question 7

Systemic complications:

Answer 7

1
> Haematological:
• Chronic haemolytic anaemia
• Crises, as above

2
> Respiratory:
• Acute chest syndrome, 
which manifests as pleuritic pain, cough,
dyspnoea, haemoptysis and fever. 
Recurrent episodes can lead to
pulmonary hypertension and 
chronic respiratory failure

3
> Cardiovascular:
• Hypertension and left ventricular hypertrophy

4
> Gastrointestinal:
• Acute sequestration syndrome of
red blood cells in the liver or spleen

• Haemosiderosis, secondary to repeated transfusions
• Gallstones, secondary to chronic haemolysis

5
> Genitourinary:
• Haematuria
• Renal failure secondary to acute papillary necrosis
• Priapism

6
> Neurological complications:
• Stroke
• Meningitis

7
> Immune system:
• Splenic infarction increases the risk of infection by encapsulated organisms including Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.
Asplenic patients must be
vaccinated against these organisms and take oral penicillin daily

8
> Eyes:
• Proliferative retinopathy

9
> Musculoskeletal:
• Deformity of skull and long bones secondary to compensatory hyperplasia
• Bone pain
• Osteomyelitis, commonly caused by Salmonella
• Avascular necrosis, most commonly affects hip joint, but other major joints may be involved

10
> Skin:
• Ulceration

11
> Chronic pain:
• Opioid tolerance
• Pain management issues

Question 8

Which investigations would help confirm a diagnosis of sickle cell anaemia?

Answer 8

> FBC:
• ↓ Hb (6–8 g/dL)
• Reticulocyte count (10–20%)

> LFTs:
• Bilirubin
> Blood film:
• Target cells
• Sickled cells
• Howell–Jolly bodies

> Sickledex test:
• Sickling is induced by the addition of sodium metabisulfite to the sample.

• This confirms only the presence of HbS but cannot differentiate between HbAS and HBSS so is only a screening test.

> Electrophoresis (definitive test)
• Determines the type and proportion of HbS present and is therefore diagnostic

Question 9

How would you prepare for and administer an anaesthetic to a patient with sickle cell disease?

Answer 9

> Pre-operative:

• Involve the haematology team.
• Assess disease severity by assessing clinical features and laboratory findings.
• For major elective intra-cavity surgery, aim for an HbS concentration of <40% and an Hb of 10–12 g/dL. This may be achieved by exchange transfusion.
• Cross-match blood early, as antibodies can be generated in response to previous transfusions.

Consequently, the process of crossmatching
maybe prolonged and it can take up to 48 hours to source suitable blood when unusual antibodies are present.

• Ensure the patient is fully vaccinated and on regular penicillin and folic acid.
• Keep nil by mouth for the minimum possible duration and prescribe intravenous fluids during this time.
• Avoid sedatives as this can cause hypoventilation leading to respiratory acidosis and hypoxia.

Question 10

> Peri-operative: `

Answer 10

Standard anaesthetic techniques may be used but

particular attention must be paid to the potential problems of
 hypoxia, 
hypothermia, 
acidosis, 
dehydration and pain.

• Oxygenation:
Pre-oxygenate patients well and maintain oxygenation
with an appropriate FiO2.

• Normothermia:

Use fluid warmers and warming blankets throughout
the procedure and minimise shivering as this consumes a vast amount of oxygen.

• Avoid circulatory stasis: Position the patient well to prevent blood stasis in dependent parts or limbs.

Avoid the use of arterial tourniquets: although not absolutely contraindicated, they should be
used with extreme caution. Maintain good cardiac output to prevent venous sludging. Ideally, vasopressors should be avoided.

• Hydration: Give intravenous fluids to maintain hydration and prevent venous sludging.
• Avoid acidosis: Ventilate to normocapnia to prevent respiratory acidosis.

• Analgesia: Maintain good analgesia as this reduces catecholamine surges and minimises oxygen consumption. Be aware that these patients may be opioid tolerant and therefore are likely to benefit from
early review by the pain management team.

• Intravenous regional anaesthesia (e.g. Bier’s block): Such techniques are absolutely contraindicated in sickle cell disease, because the prolonged venous stasis would result in sickling through
the limb.

Question 11

> Post-operative

Answer 11

: Vigilance to avoid precipitating a crisis must continue
into the post-operative period for both homo- and heterozygous patients.

• Homozygotes are not suitable candidates for day surgery and those undergoing intermediate to high-risk procedures should be considered for critical care post-operatively.
• Administer supplemental oxygen.
• Continue intravenous fluids until patient is eating and drinking.
• Ensure effective analgesia using a multimodal approach and involve the pain team.
• Avoid hypothermia.