Sickle Cell Disease Flashcards
What is Sickle Cell Anaemia?
Homozygosity for HbS
HbSS
What is Sickle Cell Disease?
Group of chronic conditions with sickling of RBCs caused by inheritance of haemoglobin S (HbS)
What is the genotype in Sickle Cell trait? How does this present?
HbAS
Asymptomatic except in conditions that favour sickling (hypoxia, dehydration)
What causes sickling of red blood cells?
Point mutation in B globin gene (Valine subs glutamic acid on position 6= non-polar so insoluble).
Results in formation of abnormal haemoglobin S
Describe the pathophysiology of sickling cells
HbS polymerises when deoxygenated, causing sickling of RBCs
Sickling makes RBC’s more fragile + inflexible
Triggered by any event associated with reduced O2 tension
Why are inflexible sickled cells pathological?
Lack elasticity + adhere to vascular endothelium
This disrupts microcirculation, causes vascular occlusion + subsequent tissue infarction.
List 4 triggers precipitating sickling of RBCs
Infection
Hypoxia
Acidosis
Dehydration
Describe the epidemiology of Sickle Cell disease
1 in 2000 births
African, Afro-Caribbean, Asian or Mediterranean
What deficiency may arise in sickle cell disease? Why? What is done to restore this?
Folate deficiency
Haemolysis + subsequent increased turnover of RBCs increases demand for folate
Give Folic Acid: If severe haemolysis or in pregnancy
Why is sickle cell disease more common in non UK populations?
Sickle cell trait confers resistance to Malaria, thus carrying HbS has a survival advantage
When do symptoms of sickle cell disease start to present?
Coincides with switch from HbF to HbA synthesis
~3-6 months
What are sickled red blood cells prone to?
Sequestration + destruction, leading to decreased RBC survival (20 days) through Extravascular (Spleen) + intravascular haemolysis
What are the acute manifestations of sickle cell anaemia?
Haemolytic crises
Infection
Vaso-occlusive events
What 2 acute haemolytic crises can occur in sickle cell disease?
Splenic sequestration crisis
Aplastic crisis
What is a splenic sequestration crisis?
Occlusion of blood flow out of spleen
Causes pooling of RBCs in spleen + splenomegaly
Results in anaemia + hypovolaemic shock
List 4 features of a splenic sequestration crisis
Acute LUQ pain
Anemia
Reticulocytosis
Intravascular volume depletion: hypotension
What 5 infections are those with sickle cell disease particularly susceptible to?
Pneumococcus Meningococcus Haemophilus Influenza Osteomyelitis: Salmonella, Staph aureus Sepsis: Strep. pneumoniae
What causes Aplastic Crises?
Infection by Parvovirus B19
infects developing red cells in BM + arrests maturation
With such reduced lifespan of RBC’s in SCD, results in dramatic fall in Hb
Why are people with sickle cell disease more susceptible to infection?
Recurrent crises causes atrophy or infarction of the spleen
Increases risk of infection with encapsulated organisms
List 5 vaso-occlusive crises in sickle cell disease
Acute chest syndrome Priapism Stroke (common in children) Infarctions of nearly any organ (esp. spleen) Avascular necrosis
What are Vaso-occlusive crises ?
Ischaemia caused by obstruction of microcirculation by sickled RBCs
List 6 symptoms of vaso-occlusive crises
Swollen painful joints + bones Abdo pain Visual loss (proliferative retinopathy) Loin pain Neuro signs e.g. Hemiplegia (Stroke) Tachypnoea
Which bones are commonly affected in adults and children by vaso-occlusion?
Adults: Ribs, Spine, Pelvis, Long bones
Children: Small bones of hand= Dactylitis
What symptom may indicate sequestration crises?
LUQ pain
Give 2 signs of sequestration crises on examination
Splenomegaly
Hypotension
Give 3 chronic features of sickle cell anaemia
Haemolytic anaemia: fatigue, weakness, pallor
Pain
Cholelithiasis (pigmented stones)
What may provoke vaso-occlusive crises?
Cold
Infection
Exertion
Dehydration
List 4 signs of vaso-occlusion and infarction
Joint or muscle tenderness or swelling (due to avascular necrosis)
Short digits: due to infarction in small bones of the hands
Retina: cotton wool spots due to retinal ischaemia
Jaundice (haemolysis)
What causes priapism in sickle cell anaemia?
Microvascular occlusion of the penis so blood can’t leave, it remains painful + erected for a long time
What characterises Acute Chest syndrome? What causes ACS?
New pulmonary infiltrate on CXR with:
fever, cough, chest pain, tachypnoea.
Vaso-occlusive crisis of the pulmonary vasculature
What investigations are performed in sickle cell disease?
Bloods: Anaemia
Blood smear
Sickle solubility test
Haemoglobin electrophoresis / HPLC
What other investigations may be used in sickle cell disease? Why?
MRI or CT Head: neuro complications
X-rays: identify avascular necrosis
Bacterial cultures: to confirm infection
CXR: if resp Sx
What is seen on a blood smear in sickle cell anaemia?
Sickle cells: crescent-shaped RBCs
Target cells
Howell-Jolly bodies
Reticulocytosis
What is a sickle solubility test?
Dithionate added to blood smear
SCD: increased turbidity (no difference between SCA or trait so need to do HPLC to confirm)
What sign may be seen on skull x-ray in sickle cell anaemia?
“Hair on end”
Which investigation gives a definitive diagnosis of sickle cell disease?
Hb Electrophoresis
Shows HbS
Absence of HbA (if homozygous HbS)
High HbF
How does reticulocyte count vary in sickle cell disease?
HIGH: in splenic sequestration crises
LOW: in aplastic crises
List 3 prophylactic measures used in management of sickle cell anaemia
Pneumococcal vaccines
Meningococcal vaccines
Daily penicillin
Give 2 indications for treatment in sickle cell anaemia with hyroxyurea
Frequent, acute painful episodes or other vaso-occlusive events
Severe symptomatic anaemia
Describe the mechanism of action of hydroxyurea in sickle cell anaemia. What adverse side effect may result from treatment with hydroxyurea?
Stimulates erythropoiesis + increases HbF HbS is proportionally reduced RBC polymerisation decreases Fewer vaso-occlusive episodes SE: Myelosuppression
What is used to prevent repeated admission due to septicaemia in febrile children?
Ceftriaxone
What drug can be used if patients are intolerant/ refractory to hydroxyurea?
L-glutamine
What treatment may be used in severe anaemia?
Red cell transfusion
When may an exchange transfusion be necessary in sickle cell patients?
Severe crises
Pre-op
Pregnancy
What advice is given to sickle cell patients?
Avoid precipitating factors
Good hygiene + nutrition
Genetic counselling
Prenatal screening
What surgical treatment may be used in some patients?
BM transplant
Joint replacement for avascular necrosis
Describe the management of acute painful crises
Oxygen
IV fluids
Strong analgesia (IV opiates)
Abx
List 9 complications of sickle cell anaemia
Cardiovascular manifestations Cholelithiasis Liver complications e.g. hepatomegaly, jaundice Leg ulcers Lung damage Poor growth in children Chronic renal failure Retinal disease Iron overload from repeated transfusion
What is the prognosis for those with sickle cell disease
Most survive to ~50 with good care
Major mortality results from pulmonary, neuro or infectious complications
