73. Sickle cell

Question 1

An unbooked Afro-Caribbean primagravida arrives on the ward in
advanced labour. Fetal distress is diagnosed and the obstetricians wish
to do an emergency caesarean section. Her full blood count shows an Hb
of 8.3 g/dl with a microcytic picture (normal platelets). Time will not
permit electrophoresis.
What may explain the blood picture?

Answer 1

A haemoglobin concentration of less than 10.5 g/dl is due to something other
than the dilutional anaemia of pregnancy. Some causes of a microcytic
anaemia with normal platelets are:

Iron deficiency

Hb SS (Sickle cell disease) – the patient would know this diagnosis
Hb AS (Sickle cell trait)
Hb SC

a-Thalassaemia
b-Thalassaemia (less common in Africans)
Some anaemias of chronic disease.

The blood film should be examined and electrophoresis should be organised
because it may influence future management.

Question 2

Sickle cell trait (AS)

Answer 2

Usually no clinical abnormality unless exposed to extreme hypoxia
(sickling if PaO2 < 15 mmHg).

Increased risk of pyelonephritis during pregnancy.

Question 3

Sickle cell haemoglobin C (SC) disease

Answer 3

Less severe clinical course than SCD but can suffer the same complications.

Prevalent in West Africans.

May not develop symptoms until late pregnancy
(splenic sequestration and marrow necrosis).

Can develop proliferative retinopathy.

Question 4

How would you manage anaesthesia for the Caesarean section?

Answer 4

Pregnancy exacerbates the complications of sickle cell anaemia. Maternal
mortality of 1% is due to pulmonary infection and infarction.
Blood transfusions are indicated for:

Severe anaemia
Hypoxaemia
Pre-eclampsia
Septicaemia
Renal failure
Acute chest pain syndrome
Anticipated surgery.

A haemoglobin concentration of 10 g/dl is commonly aimed for in patients
having a caesarean section.

Question 5

Either regional or general anaesthesia is acceptable. Principles of
management are

Answer 5

Oxygen

Crystalloids for intravascular volume

Transfusion to maintain oxygen carrying capacity

Venous stasis prophylaxis

Normothermia.

Question 6

Anaesthetic problems with Sickle cell disease

Answer 6

Avoidance of precipitants of sickle crises

Difficult i.v. access

Pain/opioid tolerance

Anaemia and high output failure

Infection (salmonella)

Psychiatric problems

Intra-operative crisis/thrombo-embolic phenomena

Acute chest syndrome

Renal impairment

Pulmonary hypertension

Question 7

Precipitants of a Sickle crisis

Answer 7

Dehydration

Hypoxia

Cold

Alcohol

Stress

Infection

Menstruation

Vascular stasis

Acidosis.

Question 8

Surgery proceeds uneventfully, but post-operatively she develops acute
pleuritic chest pain. What may be causing this

Answer 8

Possible causes
Pulmonary embolus
Acute chest syndrome
Pneumothorax
Pneumonia.

Question 9

If this were a Sickle crisis, how would you manage the case?

Answer 9

The mainstays of management of a Sickle crisis are:

Analgesia

Fluid replacement

Avoidance of hypoxia.

Question 10

Types of Sickle crisis:

Answer 10

Aplastic

Sequestration

Infarctive

Question 11

Aplastic

Answer 11

Depression of erythropoiesis secondary to infection
(esp. parvovirus) or folate deficiency in pregnancy

Question 12

Sequestration

Answer 12

This can result from massive pooling in the spleen
(esp. with SC disease).

Question 13

Infarctive

Answer 13

These are vaso-occlusive events, often in the
abdomen, back or long bones.

Question 14

Pain

Answer 14

Can be very severe (and often underestimated).

Treat with: High dose opioids (PCA may be used)

NSAIDs

Epidural

Paracetamol

Fentanyl patches

Tricyclic antidepressants

Benzodiazepines for spasms and anxiolysis.

Question 15

Dehydration

Answer 15

Causes increased haematocrit and increased sickling.

Question 16

If fever is present

Answer 16

Search for focus of infection
(cultures of blood, sputum and urine).

It may be due to the crisis itself.

Broad-spectrum antibiotics, which must cover strep. Pneumonii (hyposplenism).

Question 17

If refractory:

Answer 17

Exchange transfusion
Steroids have been used (Methylprednisolone

Question 18

Acute chest syndrome

Answer 18

Cause
Unknown exactly
? Hypoventilation due to pain from rib infarcts
? infarcted marrow embolism
? PE

Signs Acute chest pain
Fever
Cough
Basal X-ray changes
↓SaO2

Treatment O2/CPAP/IPPV
Exchange transfusion with HbS < 30% causes a response within 1–2 days

Question 19

Sickling mechanism

Answer 19

The HbS tetramer
undergoes a conformational change in the deoxygenated state
and leaves hydrophobic residues (valine instead of glutamic acid) exposed.

These react with other globin chains forming an insoluble polymer.
Hb S begins to aggregate at a PO2 of less than 50 mmHg.

The process is also time dependent.

When exposed to oxidant stress,
HbS produces free radicals that damage
the erythrocyte membrane proteins.

Abnormal adhesion to endothelium then occurs.

Infection or minor sickling events cause leucocytes to produce IL-6, IL-1
and TNF that up-regulate cell adhesion molecules (CAMs) on the vascular
endothelium.

These cause activation of the haemostatic mechanism.

Platelets and sickle reticulocytes bind easily to CAMs causing clot
formation and vascular occlusion → hypoxia → more sickling