sickle cell disease Flashcards
(31 cards)
definition of sickle cell disease
Includes compound heterozygosity for Hb S and C and for Hb S and b-thalassaemia.
sickle cell anaemia - a chronic condition with sickling of RBC caused by inheritence of HbS
sickle cell anaemia - homozygosity for HbS (SS)
sickle cell trait - carries one copy of HbS (AS) - no disability, protective from falciparum malaria. May get some sx in hypoxia - in plane or anaesthesia - need pre-op sickle test
pathology of sickle cell disease
Autosomally recessive inherited point mutation in the b-globin gene = valine substituting glutamic acid on position 6 = HbS rather than HbA
(HbA2 adn HbF are still produced)
deoxygenation of HbS alters conformation with the resulting hydrophobic interactions between adjacent HbS and formation of insoluble polymers = sickling of red cells with increased fragility (so haemolyse) and inflexibility = vaso-occulsive crisis
what are sickled cells prone to doing
sequestation and obstruction = reduced red cell survival ie 20days
occlusion in small bv = hypoxia = further sickling and occlusion
precipitating factors for sickling
infection
dehydration
hypoxia
acidosis
epidemiology of sickle cell disease
rarely presents before 4–6 months (because of continuous production of foetal haemoglobin).
Common in Africa, Caribbean, Middle East and areas with high prevalence of malaria (carrier frequency in Afro-Caribbeans 8%).
1:700 people of African descent.
what are the sx of sickle cell disease
they are secondary to vaso-occlusion or infarction:
- Autosplenectomy (splenic atrophy or infarction) = increased infection risk with encapsulated organisms - (e.g. pneumococcus, Haemophilus influenzae, meningococcus, Salmonella).
- abdo pain
- bone involvement
- myalgia and arthralgia
- CNS - fits and strokes eg hemiplegia
- retina - visual loss (proliferative retinopathy)
bone sx of sickle cell disease
painful crisis affecting small bones in hands and feet (dactylitis) in children, and ribs, spine, pelvis and long bones in adults
chronic hip and shoulder pain - avascular necrosis
sx of sequestration crisis in sickle cell disease
this is where red cells pool in various organs
- spleen
- liver = exacerbation of anaemia
- lungs = Acute chest syndrome: breathlessness, cough, pain, fever
- corpora cavernosa = persistent erection (pripiasm) and impotence
signs of sickle secondary to vaso-occlusion, ischemia or infarction
bone, joint or muscle tenderness or swelling caused by avascular necrosis
short digits from infarction in small bones
retina - cotton wool spots from areas of ischemic retina
signs of sickle cell disease secondary to sequestation crisis
organomegaly - spleen in early disease, but later decreases in size because of splenic atrophy
priapism
general signs of sickle
signs of anaemia
secondary to vaso-occlusion, ischemia, infarction
secondary to sequestration crisis
Ix for sickle cell disease
blood
blood film
sickle solubility test
haemoglobin electrophoresis
Hip XR - common site for avascular necrosis of femoral head
MRI or CT head - neuro complications
aim for dx at birth to allow for infection prophylaxis early
blood results for SCD
FBC
- anaemia 60-90g/L
- reticulocytes are high in haemolytic crisis and low in aplastic crisis
- high BR
UE
blood film in SCD
sickle cell
anisocytosis
features of hyposplenism - target cells, Howell-jolly bodies
sickle solubility test
dithionate added to blood = increased turbidity
doesnt distinguish between SS and AS
Hb electrophoresis for SCD
confirms dx
HbS, absence of HbA in HbSS and increased levels of HbF
management for acute painful crisis of SCD
oxygen
IV fluids
strong analgesia - IV opiates
AB
crossmatch blood, check FBC, and reticulocytes
septic screen - blood cultres, MSU +- CXR if high temp or chest signs
keep warm
measure PVC, reticulocytes, liver and spleen size twice daily
transfusion if Hb or reticulocytes fall sharply - helps oxygenation, as good as exchange transfusion
exchange transfusion reserved for people who are rapidly worsening
Mx of SCD
infection prophylaxis
- penicillin V.
- Regular vaccinations (e.g. against pneumococcus)
early rescue out pt AB to prevent admissions ge ceftriaxone. Consider admission if: Hb 30 ≈ 109 /L, T° >40°C, severe pain, dehydration, lung infiltration.
folic acid - in severe haemolysis or in pregnancy
hydroxyurea - increase HbF levels and reduces frequency and duration of sickle cell crisis
exchange transfusion - in severe crisis, before surgery, pregnancy
surgical
surgical Mx of SCD
bone marrow transplant in selected pts
joint replacement for avascular necrosis
advice given to SCD
avoid precipitating factors
good hygiene and nutrition
genetic counselling
prenatal screening
complications of SCD
complications of vaso-occluision and sequestration
splenic infarction before 2yrs due to microvascular occlusion = infection - aplastic crises - infection with B19 parvovirus, temporary cessation of erythropoiesis
haemolytic crisis
pigment gallstones
cholecystitis
renal papillary necrosis
leg ulcers - local ischemia
cardiomyopathy
poor growth
retinal disease
iron overload
lung damage: hypoxia -> fibrosis -> pul HTN
prognosis of SCD
most, with good care, survive to 50yrs
Major mortality is usually a result of pulmonary or neurological complications (adults) or infection (children).
vaso-occlusive crisis in SCD
common - due to microvascular occlusion
affects the marrow = severe pain
triggered by precipitants
hands and feet affected if <3yr = dactylitis
occlusion may = mesenteric ischemia - mimicking acute abdo
CNS infarction -> stroke, seizure or cognitive defetc
Transcranial doppler US indicates stroke risk - blood transfusions prevent by reducing HbS
avascular necrosis
leg ulcers
low flow priapism
priapism in SCD
from vaso-occlusive crisis
also seen in CML
may respond to hydration, a-agonists eh phenylephrine, or aspiration of blood +irrigation with saline
if for >12hr - prompt cavernosus-spongiosum shunting can prevent later impotence
