Sickle Cell Disease
Intro
Pathogenesis
Clinical features
Management
Prognosis
Prenatal Dx
Screening
commonest genetic disorder in children in many European countries - 1 in 2000
HbS inherited
point mutation in codon 6 of B-globin gene (AA change from glutamine to valine)
common in afrocaribbeans, middle east + N Europeans
Types
Sickle cell anaemia
HbSS
homozygous HbS
small amounts of HbF, no HbA
HbSC disease
HbS from 1 parent, HbC from other (different point mutation)
no HbA
Sickle B-thalassaemia
HbS from 1 parent, B-thalassaemia from other
no HbA
similar sx to sickle cell anaemia
Sickle trait
HbS from 1 parent, normal B-globin from other
asymp carrier (unless v low O2 tension)
HbS forms rigid tubular spiral bodies which deform RBCs into sickle shape
reduced lifespan
get trapped in microcirculation (vaso-occlusion) + cause ischaemia
exacerbated by cold, low O2 tension, dehydration
varies widely
most severe
all have moderate anaemia (Hb 6-10) with jaundice due to chronic haemolysis
increased susceptibility to infection
pneumococci
Hib
osteomyelitis
due to hyposplenism from chronic sickling + splenic infarcts
risk of sepsis greatest in early childhood
vaso-occlusive crises
hand foot syndrome: dactylitis (swelling), pain
common in bones of limb + spine
acute sickle chest syndrome
most serious type
can lead to severe hypoxia, need for ventilation + emergency transfusion
AVN of fem heads
can be precipitated by cold, dehydration, excess exercise, hypoxia, infection, stress
acute anaemia
sudden Hb drop
causes
haemolytic crisis (sometimes due to infection)
aplastic crisis (sometimes due to parvovirus B19)
sequestration crisis (sudden spleen/liver enlargement, abdo pain, due to accumulation of sickled cells in spleen)
Priapism
needs to be txed quick with exchange transfusion to prevent fibrosis of corpora cavernosa + ED
prolonged erection
splenomegaly
common in young children, less frequent in older children
Long term problems
short stature
delayed puberty
stroke - 1 in 10
cognitive issues - 1 in 5
subtle neuro damage
poor concentration + school performance
adenotonsillar hypertrophy
sleep apnoea
nocturnal hypoxaemia
chronic anaemia can lead to cardiomegaly + HF
renal dysfunction
pigment gallstones
leg ulcers uncommon in children
psychosocial problems e.g. time off school
Immunisations (pneumo, Men, Hib)
daily PO penicillin throughout childhood
once daily folic acid (increased requirement due to chronic haemolysis)
avoid exposure to cold, dehydration, excess exercise, stress, hypoxia
dress children warmly
make sure they have enough fluids esp before exercise
take extra care to keep them warm after swimming/playing outside
For vaso-occlusive crises give analgesia (sometimes opiates requireed), fluids, +/- antibiotics +/- O2 if needed
exchange transfusion for acute chest syndrome, stoke, priapism
if lots of crises give hydroxyurea
increases HbF production
prevents further crises
requires monitoring for SEs (WBC suppression)
if no response to hydroxyurea can offer BM transplant
90% cure rate
5% fatality risk
need HLA identical sibling
HbSS - 50% dead before 40
mortality rate in childhood only 3% - usually due to bacterial infection
Guthrie test
good as early dx allows penicillin prophylaxis in infancy
CVS
may develop proliferative retinopathy in adolescence - check eyes regularly
prone to osteonecrosis of hips + shoulders
no risk with GA, just avoid hypoxia