Sickle Cell Anaemia Flashcards
what is the definition of sickle cell anaemia?
Disorder affecting beta haemoglobin in RBCs
what is the epidemiology of sickle cell anaemia?
Common throughout africa, follows patterns of malaria (sickle cell carriers have resistance against bad forms of malaria, don’t tend to die from malaria)
Also common in india, middle east, southern europe
what is the aetiology of sickle cell anaemia?
Autosomal recessive inherited disorder, 1 in 4 chance of disease, 50% chance of carrier, 1 in 4 chance being disease free
what are the risk factors for sickle cell anaemia?
African
Family history
what is the pathophysiology of sickle cell anaemia?
Single point mutation in β globin gene → HbS (adenine to thymine, valine subbed for glutamic acid at the 6th codon of the beta globin chain
Autosomal recessive: HbSS / compound heterozygote
HbS polymerises when deoxygenated
Blocks blood vessels – ischaemia, sequestration
Chronic haemolysis – low baseline Hb
Acute complications and chronic organ damage
- In the heterozygous state (sickle cell trait), only one chromosome carries the gene - these are carriers of the disease
- In the homozygous state (SICKLE CELL ANAEMIA), both genes are abnormal
what are the key presentations of sickle cell anaemia?
Pain, varying in frequency depending on patient
what are the signs of sickle cell anaemia?
Sickle cell trait = protection against falciparum malaria
Sickle cell anaemia = CNS infarction, stroke, seizures
Pulmonary crisis
COPD / pulmonary hypertension, hypoxia
Infection
Enlarged spleen, fibrotic and non-functioning
Children short and underweight, delayed puberty
Avascular necrosis
Osteomyelitis
Cardiomegaly / MI
Chronic hepatomegaly
Chronic tubulointerstitial nephritis
Retinopathy
Spontaneous abortion in pregnancy
Bone marrow aplasia
what are the symptoms of sickle cell anaemia?
Sickle cell trait = no symptoms Sickle cell anaemia = acute pain in hands and feet Pain in long bones Shortness of breath, chest pain Pain in spleen Fits
what are the first line investigations for sickle cell anaemia?
FBC - Hb in range of 60-80g/L
Blood film = sickle erythrocytes shown
Sickle solubility test (not diagnostic, positive for both carriers (trait) and diseased
what are the gold standard investigations fro sickle cell anaemia?
Hb separation (all separate types of Hb an individual has based on size and charge of molecule, e.g. HbS peaks only = sickle cell, HbS and HbA = carrier, HbA only = no sickle cell) NOT DIAGNOSTIC, not confirmatory o HPLC o Capillary electrophoresis o Gel electrophoresis o Isoelectric focusing
what other tests could be done for sickle cell anameia?
Antenatal: molecular genetics
what are the differential diagnoses for sickle cell anaemia?
Valvular heart disease, septic arthritis, sepsis
how is sickle cell anaemia managed?
Precipitating factors such as infection, cold and dehydration should be avoided or treated quickly e.g prophylaxis vaccines
- FOLIC ACID to all haemolysis patient
- Acute painful attacks:
• IV fluids
• Analgesia - morphine, codeine, paracetamol and NSAIDs
• Oxygen and antibiotics if required
- Anaemia:
• Blood transfusion given for: Acute chest syndrome, Acute anaemia due to acute splenic sequestration, aplastic crisis, Stroke, Heart failure (Note: increased risk of iron overload)
Oral HYDROXYCARBAMIDE: Increases HbF concentrations
• Stem cell transplant
how is sickle cell anaemia monitored?
Supportive
o stay warm and hydrated
o vaccinations and antibiotics
o monitoring including transcranial dopplers
Regular blood transfusion – exchange / top up
Hydroxycarbamide - ↑ HbF
New drugs: crizanlizumab, voxelotor
Transplant only curative therapy currently available
Genetic therapies – in clinical trials
what are the complications of sickle cell anaemia?
Stroke (ischaemic or haemorrhagic)
Acute painful crisis (= veno occlusive crisis / VOC)
Gallstones
Hyposplenism – Risk of sepsis
Retinal bleed / detachment
liver / kidney failure
Leg ulcers
Cardiac failure
pulmonary hypertension
Acute chest syndrome (treated with red cell exchange transfusion)
Sequestration (blood pools in liver / spleen)
Acute anaemia: Haemolytic crisis, viral infection, sequestration
Priapism
VTE
