Sickle cell disease

Question 1

Define:

Answer 1

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

Sickle cell disease = trait and Hbs

Question 2

Aetiology/risk factors:

Answer 2

• 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

This leads to Sickling makes the red cells more fragile and inflexible - more prone to sequestration and destruction.

Question 3

What are the factors that precipitate sequestration:

Answer 3

I HAD
Infection 
Hypoxia
Acidosis
Dehydration

Question 4

Epidemiology:

Answer 4

Will not present till after 4-6 months are there HbF predominates before this.

Common in areas with high prevalence of malaria such as - Africa, carribean and middle east

Question 5

Symptoms:

Answer 5

o Autosplenectomy (splenic atrophy or infarction) - Leads to increased risk of infections with encapsulated organisms (e.g. pneumococcus, meningococcus)
o Abdominal Pain due to mesenteric ischaemia
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
• Avascular necrosis
o Myalgia and Arthralgia
o Leg ulcers
o Low flow priapism
o CNS
• Fits and strokes, cognitive defects
o Retina
• Visual loss (proliferative retinopathy)

Question 6

Symptoms of sequestration crisis:

Answer 6

o	NOTE: sequestration crises occur due to pooling of red cells in various organs (mainly the spleen). Mainly affects children as spleen has not yet undergone atrophy.
o	Liver --> exacerbation of anaemia 
o	Lungs --> acute chest syndrome
•	Breathlessness 
•	Cough 
•	Pain 
•	Fever 
o	Corpora cavernosa
•	Persistent painful erection (priapism)
•	Impotence

Question 7

Signs of aplastic anaemia:

Answer 7

due to parvovirus B19 with sudden reduction in marrow production, especially RBCs
Anaemia and infection

Question 8

Signs:

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

• Retina - cotton wool spots due to retinal ischaemia

Question 9

Signs of sequestration crisis:

Answer 9

• 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 10

Investigations:

Answer 10

o FBC - Low Hb
• Reticulocytes: HIGH - in haemolytic crises but LOW - in aplastic crises
o U&Es
• Blood Film -Sickle cells , Anisocytosis (variation in size of red cells)
o Features of Hyposplenism:
• Target cells
• Howell-Jolly bodies

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

Haemoglobin Electrophoresis
o Shows HbS , Absence of HbA (if homozygous HbS, 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 11

Management of acute painful crisis:

Answer 11

o	Oxygen
o	IV Fluids 
o	Strong analgesia (IV opiates)
o	Antibiotics
o	Cross match blood 
o	Give transfusion if Hb or reticulocytes fall sharply

Question 12

Management:

Answer 12

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

• Folic Acid-If severe haemolysis or in pregnancy

Hydroxyurea/Hydroxycarbamide –
o Increases HbF levels

• Red Cell Transfusion
o For SEVERE anaemia

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

• Surgical
o Bone marrow transplantation – may be curative + Joint replacement in cases with avascular necrosis

Question 13

Complications:

Answer 13

•	Infection
•	Poor growth in children
•	Chronic renal failure
•	Haemolytic crises 
•	Pigment gallstones 
•	Retinal disease
•	Cholecystitis 
•	Renal papillary necrosis 
•	Leg ulcers 
•	Cardiomyopathy
•	Iron overload from repeated transfusion 
•	Lung damage
 Aplastic crisis

Question 14

What is aplastic crisis:

Answer 14

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)

Question 15

Prognosis:

Answer 15

• 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