Sickle cell anaemia

Question 1

What is sickle cell anaemia

Answer 1

Hereditary deformation of RBC as a result of faulty haemoglobin molecule

Question 2

Epidemiology of Sickle cell anaemia

Answer 2

More common in African populations

Sickle cell trait protects against malaria

Question 3

Inheritance pattern of sickle cell anaemia

Answer 3

Autosomal recessive

50% chance of being a carrier; 1 in 4 chance of disease (is 2 carrier parents)

Question 4

What is the difference between sickle cell anaemia and sickle cell trait

Answer 4

Sickle cell trait = heterozygous state - only one chromosome carries gene
Sickle cell anaemia - homozygous state - both genes are abnormal

Question 5

Why does sickle cell anaemia not manifest itself until about 6 months of age?

Answer 5

Since the synthesis of HbF (gamma or fetal) is normal, the disease does not manifest itself until the HbF decreases to adult levels at about 6 months of age

Question 6

Pathophysiology of Sickle cell anaemia

Answer 6

Sickle cell haemoglobin (HbS) results from a SINGLE-BASE MUTATION of ADENINE to THYMINE which produces a substitution of VALINE for
GLUTAMIC ACID at the SIXTH CODON of the beta-globin chain.
HbS is insoluble and polymerises when
deoxygenated.
Flexibility of the cells is decreased and they become rigid and take up their characteristic sickle appearance.
This process is initially reversible but, with repeated sickling, the cells
eventually lose their membrane flexibility and become IRREVERSIBLY
SICKLED
The irreversibly sickled cells are dehydrated and dense, and will not return to normal when oxygenated.

Question 7

True or False:
HbS releases its oxygen to the tissues less readily than normal RBCs and patients thus feel poor as well as being anaemic (except during crises or complications)

Answer 7

False
HbS releases its oxygen to the tissues MORE readily than normal RBCs and
patients thus feel well despite being anaemic (except during crises or
complications)

Question 8

What can precipitate sickling

Answer 8

Infection
Dehydration
Cold
Acidosis
Hypoxia

Question 9

What can result from sickling

Answer 9

A shortened RBC survival resulting in haemolysis.
Impaired passage of cells through the microcirculation, leading to obstruction of small vessels and tissue infarction and thus intense pain.

Question 10

Clinical presentation of Sickle cell trait

Answer 10

Asymptomatic with no disability except in hypoxia e.g. in unpressurised aircraft or anaesthesia when vaso-occlusive events may occur.

Can offer protection against *Falciparum Malaria

Question 11

Clinical presentation of Sickle cell anameia

Answer 11

Vaso-occlusion
Early childhood acute pain in hands and feet due to occlusion of small vessls and avascular necrosis of the bone marrow.
In adults this affects the long bones, ribs, spine and pelvis.
Variable frequency.
Avascular necrosis -> shortened bones in children

Also acute chest syndrome in 30% (vaso-occlusive crisis of pulmonary vasculature) and pulmonary hypertension in 10%

Anaemia symptoms

Question 12

What is most common cause of death in adults with sickle cell disease

Answer 12

Pulmonary hypertension

Chronic lung disease

Question 13

What can cause an acute fall in Hb level in sickle cell anaemia

Answer 13

Splenic sequestration (where sickle cells get trapped in spleen due to their shape)

Bone marrow aplasia (commonly follows viral infection of erythroid progenitors meaning no reticulocytes in peripheral blood due to failure of eryhtropoiesis in the marrow - aplastic crisis)

Question 14

Long term problems of Sickle cell anaemia

Answer 14

Growth and development:

• young children are short but regain height by adulthood
• remain below normal weight
• sexual maturation is delayed

Bones:

• common sites of vaso-occlusive crises resulting in chronic infarcts
• Avascular necrosis of the hips and shoulders, compression of vertebrae and shortening of bones in the hands and feet occur
• Osteomyelitis can occur due to Staphylococcus Aureus, Staph. pneumoniae and salmonella

Infection in bones, lungs and kidneys (most susceptible to vaso-occlusive crisis)
Cardiac problems
Impaired placental blood flow
Retinopathy etc
Nephritis
Chronic hepatomegaly and liver dysfunction
Neurological problems - TIA etc

Question 15

Diagnosis of Sickle cell anaemia

Answer 15

Neonatal screening
Blood count - raised reticulocyte, low Hb
*Blood films - sickled erythrocytes shown
Sickle solubility test will be Positive
Hb electrophoresis - confirm diagnosis

Question 16

What is expecting Hb concentration in SCA in blood count

Answer 16

60-80g/L

Question 17

How is Hb electrophoresis used to confirm SCA diagnosis

Answer 17

80-95% HbS and absent HbA shown

Aim for diagnosis at birth (cord blood) to aid prompt pneumococcal prophylaxis

Question 18

Treatment of SCA

Answer 18

Folic acid
Pain relief
BMT in severe disease

Question 19

What could be given for acute painful attacks in SCA

Answer 19

IV fluids
Analgesia - morphine, codeine, paracetamol, NSAIDs
Oxygen and antibiotics if required

Question 20

SCA - what could be done for anaemia treatment

Answer 20

Blood transfusion in cases
*Oral Hydroxycarbamide to increase HbF concentrations
(Stem cell transplant)

Question 21

In aplastic anaemia due to bone marrow failure, when would you treat with immunosuppressive therapy and give an example of the therapy

Answer 21

Immunosuppressive therapy with ANTITHYMOCYTE GLOBULIN (ATG) and
CICLOSPORIN in those:
• Over 40
• Below 40 with severe disease who do not have a HLA identical sibling donor
• Those who are transfusion dependent