Sickle Cell Disease Flashcards
Definition
A chronic condition with sickling of red blood cells caused by inheritance of haemoglobin S (HbS)
Types
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
Aetiology
• 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
Factors that precipitate sickling
o Infection
o Dehydration
o Hypoxia
o Acidosis
Epidemiology
- 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
Presenting symptoms (secondary to vaso-occlusion or infarction)
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)
Presenting symptoms (sequestration crisis)
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
Signs on physical examination
• 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
Investigations (bloods)
o FBC • Low Hb • Reticulocytes: ▪ HIGH - in haemolytic crises ▪ LOW - in aplastic crises
o U&Es
Investigations (blood film)
o Sickle cells
o Anisocytosis (variation in size of red cells)
o Features of Hyposplenism:
• Target cells
• Howell-Jolly bodies
Investigations (other)
• 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
Management plan (acute painful crises)
ACUTE (PAINFUL CRISES)
o Oxygen
o IV Fluids
o Strong analgesia (IV opiates)
o Antibiotics
Management plan (advice)
Avoid precipitating factors,
good hygiene and nutrition,
genetic counselling,
prenatal screening
Management plan (surgical)
o Bone marrow transplantation
o Joint replacement in cases with avascular necrosis
Management plan (other)
• 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