Sickle Cell disease Flashcards
Define sickle cell disease?
Sickle cell anaemia is caused by an autosomal-recessive single gene defect in the beta chain of haemoglobin, which results in production of sickle cell haemoglobin (HbS).
outline the different genotypes for sickle cell disease?
- sickle cell anaemia = Homozygoes HbSS
- Sickle cell trait= carrier of one copy of HbS therefore HbAS
- Sickle cell diseae= 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) - HbSC
- Beta-thalassemia – HbS/Bthal
describe the disease severity of sickle cell trait?
Causes no disability (except in hypoxia e.g. anaesthesia, high altitudes and extreme exertion – may cause vaso-occlusive event)
-protects from falciparum malaria
what is HbC?
Abnormal haemoglobin in which glutamic acid is replaced by lysine at the 6th position in the beta-globin chain
what are the factors that precipitate sickling?
IHAD
infection
hypoxia
acidosis
dehydration
outline the aetiology of sickle cell disease?
Autosomal recessive
Point mutation in the beta-globin generesulting in the substitution of glutamic acid in position 6 by valine (non-polar so insoluble)-> results in formation of abnormal HbS
Deoxygenationof HbS alters the conformation resulting in sicklingof red cells – can polymerize and form fibres known as tactoids
Sickling makes the red cells more fragile and inflexible
Once dehydrated the sickled cells adhere to the vasc endo more(particularly the post-capillary venules)
These sickled red cells are prone to:
Sequestration and destruction (reduced red cell survival ~ 20 days)
Occlusion of small blood vessels causing hypoxia, which leads to further sickling and occlusion
what is the point mutation in sickle cell disease?
point mutation in the beta-globin gene resulting in the substitution of glutamic acid in position 6 by valine (non-polar so insoluble)
summarise the epidemiology of sickle cell disease?
Rarely presents before 4-6 months (because HbF can compensate for the defect in adult haemoglobin)
Common in Africa, Caribbean, Middle-Eastand other areas with a high prevalence of malaria
what are the presenting symptoms of sickle cell disease?
what are the signs of sickle cell disease on physical examination?
Signs secondary to VASO-OCCLUSION, ISCHAEMIA or INFARCTION
- Bone - 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 – indication of haemolysis
Signs secondary to SEQUESTRATION CRISES
Signs of anaemia
what are the signs secondary to sequestrian crises?
Organomegaly
- spleen is enlarged in early disease
- later on spleen will reduce in size due to splenic atrophy
Priapism
- Microvascular occlusion of the penis so blood can’t leave and it remains painful and erected for a long time
what are the symptoms of sickle cell disease secondary to vaso-occlusion or infarction?
Autosplenectomy ( splenic atrophy or infarction) - leads to increased risk of infections with encapsulated organisms ( eg pneumococcus meningococcus)
Abdominal pain - due to messenteric ischaemia
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
which bones are affected in painful crises in children?
small bones of hands and feet- cause dactylitis in children
which bones are mainly affected in painful crises in adults?
ribs, spine, pelvis and long bones
what are the symptoms of avascular necrosis in sickle cell disease?
Myalgia and Arthralgia
Leg ulcers
Low flow priapism
CNS
what are the symptoms of sickle cell disease that affect the lungs?
ACUTE CHEST SYNDROME
- breathlessness
- cough
- fever
- pain
what are the appropriate investigations for sickle cell disease?
bloods
blood film
sickle solubility test
Haemoglobin electrophoresis= DEFINITIVE
Hip X ray
Describe blood results in sickle cell disease?
FBC
- Leukocytosis is a presentation in infants
- Low Hb
- Reticulocytes: HIGH - in haemolytic crises, LOW - in aplastic crises
U&Es
describe blood film in sickle cell disease?
sickle cells
anisocytosis ( variation in size of red cells)
Features of hyposplenism
- Target cells
- Howel-Jolly bodies
what are the results for the sickle cell solubility test?
Shows HbS
Absence of HbA (if homozygous HbS)
High HbF
What may be seen on the hip x ray in sickle cell disease?
Femoral neck is a common place for avascular necrosis
What investigations should you consider for sickle cell disease?
MRI or CT Head - If there are neurological complications
Plain X-rays of long bones – to confirm presence of bone infarction
Bacterial cultures – to confirm infection (can cause sickle cell crisis)
CXR – if resp symptoms present
How do you manage an acute ( painful crises) for sickle cell disease?
Oxygen
IV Fluids – V IMPORTANT
Strong analgesia(IV opiates – codeine or morphine(children))
- Can also give subcut analgesia
- Many cause pruritus which should be managed with diphenhydramine (anti-histamines)
- PCA – Patient controlled analgesia
Antibiotics
Cross match blood
Give transfusion if Hb or reticulocytes fall sharply
outline the management for sickle cell disease?
ACUTE (PAINFUL CRISES)
- Oxygen
- IV Fluids – V IMPORTANT
- Strong analgesia (IV opiates – codeine or morphine(children))
- Antibiotics
- Cross match blood
- Give transfusion if Hb or reticulocytes fall sharply
Infection Prophylaxis– as splenic infarction leads to hyposplenism
- Penicillin V
- Regular vaccinations (particularly against capsulated bacteria e.g. pneumococcus)
Folic Acid-If severe haemolysis or in pregnancy
Hydroxyurea/Hydroxycarbamide– if frequent crises
- Increases HbF levels
- Reduces the frequency and duration of sickle cell crisis
- Most common complication is neutropenia and hepatic/renal impairment
- Contraindicated in BM suppressive disorders e.g. leukopenia and thrombocytopenia
- For patients who are intolerant ro hydroxycarbamide, L-glutamine can be given but this should be avoided in patients with renal or hepatic impairment
Red Cell Transfusion
- For SEVERE anaemia
- Repeated transfusions (with iron chelators) may be required in patients suffering from repeated crises
Advice
- Avoid precipitating factors, good hygiene and nutrition, genetic counselling, prenatal screening
Surgical
- Bone marrow transplantation – may be curative
- Joint replacement in cases with avascular necrosis
Febrile children may risk septicaemia – repeated admission can be avoided with ceftriaxone (AB)
what are the possible complications of sickle cell disease?
Aplastic crises
- 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)
Cholelithiasis and liver complications
Infection
Leg ulcers
Lung damage
Opioid dependence
Poor growth in children
Chronic renal failure
Haemolytic crises
Pigment gallstones
Retinal disease
Renal papillary necrosis
Cardiomyopathy
Iron overload from repeated transfusion - Treat with desafirox (oral) as venesection in pts with SCA is almost impossible and pt is anaemic!!!
what is the cause of aplastic crises in patients with sickle cell disease?
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)
summarise the prognosis of patients with sickle cell disease?
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:
- Pulmonary or neurological complications in ADULTS
- Infection in CHILDREN
