Sickle cell disease Flashcards
Define
Chronic condition with sickling of RBCs caused by inheritance of haemoglobin S – hence the production of abnormal β globin chains
(1) Sickle cell anaemia (HbSS) – homozygosity for Hb S
(2) Sick cell trait (HbAS) – carries one coy of Hb S, causes no
disability except in hypoxia (e.g. anaesthesia, or unpressurised aircraft) where vaso-occlusive events may occur
(3) Sickle cell disease – heterozygotes with genes coding for other Hb variance (e.g. HbC leading to HbSC, or β- thalassaemia trait leading to HbS/βthal), symptomatic sickling seen
Note: sickle cell trait protest from falciparum malaria →AUTOSOMAL RECESSIVE inheritance
Causes
Due to an amino acid substitution in the gene coding for the β chain(Glu→Valatposition6)–resulting intheproductionof HbS rather than HbA
HbS polymerises when deoxygenated, causing RBCs to deform, producing sickle cells
These abnormal cells are fragile and haemolyse
They also block small vessels
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
Factors that precipitate sickling:
- Infection
- Dehydration
- Hypoxia
- Acidosis
(HbA2 and HbF are still produced)
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
Symptoms
Symptoms 2ndary to vaso-occlusion or infarction
- Auto-splenectomy due to splenic atrophy or infarction – leads to ↑infection risk by encapsulated organisms (e.g. pneumococcus, Haemophilus influenzae, meningococcus, Salmonella)
- Abdominal pain
- Myalgia and arthralgia
- CNS – can cause seizures or strokes from infraction
- Retina – visual loss (proliferative retinopathy)
Symptoms of sequestration crisis (RC pooling in organs)
- Liver → exacerbation of anaemia
- Lungs → acute chest syndrome: SOB, cough, pain, fever
- Corpora cavernosa → persistent erection (priapism) and
impotence
Sickle cell crisis types
↘ Vaso-occlusive ‘painful’ crisis: severe pain triggered by cold, dehydration, infection, hypoxia
↘ Aplastic crisis: due to parvovirus B19, sudden ↓BM production, usually self-limiting (2 weeks)
↘ Sequestration crisis – mainly in children, pooling in spleen leads to organomegaly, severe anaemia and shock
Signs
Signs of anaemia seen → e.g. pallor, signs of hyper-dynamic circulation (if severe), such as tachycardia, flow murmurs, cardiac enlargement
2ndary to vaso-occlusions, ischemia, infarction
- Bone → joint or muscle tenderness/swelling due to avascular necrosis (e.g. femoral head necrosis or leg ulcers), short digits (from infarction in small bones)
- Retina → cottonwool spots from areas of ischemic retina
2ndary to sequestration crisis
- Organomegaly (spleen initially enlarged then reduces in size)
- Priapism
Investigations
Bloods
- FBC
- Low Hb
- Reticulocytes:
- HIGH - in haemolytic crises
- LOW - in aplastic crises
- U&Es
Blood Film
- Sickle cells
- Anisocytosis (variation in size of red cells)
Features of Hyposplenism:
- Target cells
- Howell-Jolly bodies
Sickle Solubility Test
- Dithionate is added to the blood
- In sickle cell disease you get increased turbidity
Haemoglobin Electrophoresis
- Shows HbS
- Absence of HbA (if homozygous HbS)
- High HbF
Hip X-Ray
- Femoral head is a common site of avascular necrosis
MRI or CT Head
- If there are neurological complications
Treatment
ACUTE (PAINFUL CRISES)
- Oxygen
- IV Fluids
- Strong analgesia (IV opiates)
- Antibiotics
Infection Prophylaxis
- Penicillin V
- Regular vaccinations (particularly against capsulated bacteria e.g. pneumococcus)
Folic Acid
- If severe haemolysis or in pregnancy
Hydroxyurea/Hydroxycarbamide
- Increases HbF levels
- Reduces the frequency and duration of sickle cell crisis
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
- Joint replacement in cases with avascular necrosis
Complications
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)
Haemolytic crises
Pigment gallstones
Cholecystitis
Renal papillary necrosis
Leg ulcers
Cardiomyopathy
Prognosis
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
