Sickle Cell Disease

Question 1

Definition

Answer 1

A chronic condition with sickling of red blood cells caused by inheritance of
haemoglobin S (HbS)

Question 2

Types

Answer 2

o Sickle Cell Anaemia = Homozygous HbS

o Sickle Cell Trait = Carrier of one copy of HbS

o Sickle Cell Disease = includes compound heterozygosity for HbS and:
• HbC (abnormal haemoglobin in which glutamic acid is replaced by lysine at the 6th position in the beta-globin chain)
• Beta-thalassemia

Question 3

Aetiology

Answer 3

• Autosomal recessive
• Caused by a point mutation in the beta-globin gene resulting in the substitution of
glutamic acid in position 6 by valine
• This results in the formation of abnormal haemoglobin S
• Deoxygenation of HbS alters the conformation resulting in sickling of red cells
• Sickling makes the red cells more fragile and inflexible

• These sickled red cells are prone to:
o Sequestration and destruction (reduced red cell survival ~ 20 days)
o Occlusion of small blood vessels causing hypoxia, which leads to further sickling and occlusion

Question 4

Factors that precipitate sickling

Answer 4

o Infection
o Dehydration
o Hypoxia
o Acidosis

Question 5

Epidemiology

Answer 5

• Rarely presents before 4-6 months (because HbF can compensate for the defect in adult haemoglobin)
• Common in Africa, Caribbean, Middle-East and other areas with a high prevalence of malaria

Question 6

Presenting symptoms (secondary to vaso-occlusion or infarction)

Answer 6

Symptoms secondary to VASO-OCCLUSION or INFARCTION:

o Autosplenectomy (splenic atrophy or infarction)
• Leads to increased risk of infections with encapsulated organisms (e.g. pneumococcus, meningococcus)

o Abdominal Pain

o Bones
• Painful crises affect small bones of the hands and feet causing dactylitis in
CHILDREN
• Painful crises mainly affect the ribs, spine, pelvis and long bones in ADULTS

o Myalgia and Arthralgia

o CNS
• Fits and strokes

o Retina
• Visual loss (proliferative retinopathy)

Question 7

Presenting symptoms (sequestration crisis)

Answer 7

Symptoms of SEQUESTRATION CRISIS
o NOTE: sequestration crises occur due to pooling of red cells in various organs (mainly the spleen)

o Liver –> exacerbation of anaemia

o Lungs --> acute chest syndrome
• Breathlessness
• Cough
• Pain
• Fever

o Corpora cavernosa
• Persistent painful erection (priapism)
• Impotence

Question 8

Signs on physical examination

Answer 8

• Signs secondary to VASO-OCCLUSION, ISCHAEMIA or INFARCTION
o Bone - joint or muscle tenderness or swelling (due to avascular necrosis)
o Short digits - due to infarction in small bones of the hands
o Retina - cotton wool spots due to retinal ischaemia

• Signs secondary to SEQUESTRATION CRISES
o Organomegaly
• The spleen is ENLARGED in early disease
• Later on, the spleen will reduce in size due to splenic atrophy
o Priapism

• Signs of anaemia

Question 9

Investigations (bloods)

Answer 9

o FBC
• Low Hb
• Reticulocytes:
▪ HIGH - in haemolytic crises
▪ LOW - in aplastic crises

o U&Es

Question 10

Investigations (blood film)

Answer 10

o Sickle cells

o Anisocytosis (variation in size of red cells)

o Features of Hyposplenism:
• Target cells
• Howell-Jolly bodies

Question 11

Investigations (other)

Answer 11

• Sickle Solubility Test
o Dithionate is added to the blood
o In sickle cell disease you get increased turbidity

• Haemoglobin Electrophoresis
o Shows HbS
o Absence of HbA (if homozygous HbS)
o High HbF

• Hip X-Ray
o Femoral head is a common site of avascular necrosis

• MRI or CT Head
o If there are neurological complications

Question 12

Management plan (acute painful crises)

Answer 12

ACUTE (PAINFUL CRISES)

o Oxygen
o IV Fluids
o Strong analgesia (IV opiates)
o Antibiotics

Question 13

Management plan (advice)

Answer 13

Avoid precipitating factors,
good hygiene and nutrition,
genetic counselling,
prenatal screening

Question 14

Management plan (surgical)

Answer 14

o Bone marrow transplantation

o Joint replacement in cases with avascular necrosis

Question 15

Management plan (other)

Answer 15

• Infection Prophylaxis
o Penicillin V
o Regular vaccinations (particularly against capsulated bacteria e.g. pneumococcus)

• Folic Acid
o If severe haemolysis or in pregnancy

• Hydroxyurea/Hydroxycarbamide
o Increases HbF levels
o Reduces the frequency and duration of sickle cell crisis

• Red Cell Transfusion
o For SEVERE anaemia
o Repeated transfusions (with iron chelators) may be required in patients suffering from repeated crises

Question 16

Possible complications

Answer 16

• Aplastic crises
o Infection with Parvovirus B19 can lead to a temporary cessation of
erythropoiesis (which can cause red cell count to plummet in sickle cell patients because their red cells have a shortened life span and can’t tolerate a cessation
of erythropoiesis)

• Haemolytic crises
• Pigment gallstones
• Cholecystitis
• Renal papillary necrosis
• Leg ulcers
• Cardiomyopathy

Question 17

Prognosis

Answer 17

• Most patients with sickle cell disease who manage their disease well will survive until around the age of 50 yrs

• Mortality is usually the result of:
o Pulmonary or neurological complications in ADULTS
o Infection in CHILDREN