Sickle Cell Disease

Question 1

Define sickle cell disease

Answer 1

A group of autosomal recessive haemoglobin disorders characterised by single gene defects
in the beta chain of HbA -> sickle cell haemolglobin (HbS)

Question 2

What are the causes/risk factors of sickle cell disease?

Answer 2

Autosomal recessive
Point mutation at codon 6 of beta-globin gene -> glutamate (polar, soluble) is replaced by
valine (non-polar, insoluble) -> haemoglobin S

Deoxygenation -> polymerisation of HbS -> sickling of RBCs with ↑ fragility and inflexibility

• Sequestration and haemolysis of RBC (reduced RBC lifespan ~20 days)
• Occlusion of small vessels -> hypoxia -> further sickling and occlusion

Sickling is triggered by:
• Infection
• Exertion
• Dehydration
• Hypoxia
• Acidosis
• Stress

Question 3

What are the signs and symptoms of sickle cell disease?

Answer 3

Anaemia
• Failure to thrive
• Fatigue
• Pallor
• Tachycardia
• Cardiac flow murmur

Brain
• Stroke
• Cognitive impairment

Eyes
• Proliferative retinopathy ->
haemorrhage -> retinal
detachment -> visual loss

Heart
• Cardiomyopathy

Lungs
• Pulmonary hypertension
(intravascular haemolysis -> free
plasma Hb scavenges NO ->
pulmonary vasoconstriction)

Hepatobiliary
• Gallstones
• Jaundice

Spleen
• Hyposplenism -> ↑ susceptibility to infection e.g. pneumococcus

Bones
• Dactylitis
• Shortening of digits
• Osteomyelitis
• Chronic shoulder or hip pain (avascular necrosis)

Rheumatological
• Myalgia/arthralgia
• Skin ulceration

Genitourinary
• Haematuria (papillary necrosis)
• Renal failure (chronic glomerular damage)
• Hyposthenuria (dilute urine -> dehydration -> sickling -> painful crises)
• Priapism

Crises
• Splenic sequestration crisis – pooling in spleen -> splenomegaly, abdominal pain,
low Hb, hypovolaemic shock
• Aplastic crisis – parvovirus B19 infects red cell precursors -> arrested RBC
development -> low Hb and reticulocytopenia
• Acute chest syndrome – SOB, cough, pain, fever

Question 4

What investigations are carried out for sickle cell disease?

Answer 4

• Bloods
- FBC – low Hb, reticulocytosis (or
reticulocytopenia in aplastic crisis)
- U&Es
• Blood film
- Sickle cells
- Boat cells
- Target cells
- Howell-Jolly bodies
• Sickle solubility test
• Haemoglobin electrophoresis
• Hip X-ray – avascular necrosis
• MRI/CT head

Question 5

What is the management for sickle cell disease?

Answer 5

Acute painful crises
• Oxygen – if hypoxic
• IV fluids – rehydration
• Analgesia (opioids)
• Antibiotics – if evidence of infection
• Keep warm
• Red cell transfusion – severe anaemia, crises
• Exchange transfusion – severe crises e.g. acute chest syndrome, stroke

Long-term conservative
• Folic acid (haemolysis -> huge RBC turnover)
• Penicillin and regular vaccinations
• Hydroxyurea (↑ HbF -> reduces sickling)
• Advice – avoid precipitants

Surgical
• Bone marrow transplant if <16 years with severe disease
• Joint replacement (avascular necrosis)

Question 6

What are the complications of sickle cell disease?

Answer 6

• Complications of vaso-occlusion and sequestration.
• Aplastic crises
• Gallstones and cholecystitis
• Renal papillary necrosis
• Leg ulcers
• Cardiomyopathy