Sickle Cell Flashcards
What do you ask about history of current episode for sickle cell disease?
Site(s) of pain
it is their usual sickle pain ?precipitant
What painkillers have they already taken
What do you ask a sickle patient in a history of their sickle?
usual place of care
genotype - HbSS or HbSC
How do you assess the clinical severity of a patients sickle history?
frequency and severity of sickle crises
previous complications, especially acute chest syndrome
previous ITU admissions
Transfusions - regular, episodic, when and where last transfused, any previous reactions?
What do you look for O/E of a sickle patient?
pulse, bp, O2 sats (on air), temp, RR listen to the chest - lungs, heart palpate for liver and spleen size pallor jaundice skin- ulcers bony pains/joints - look for swelling
What is the genetics behind sickle cell?
AR point mutation in beta-globin gene on Chr 11: single nucleotide substitution GAG for GTG = A --> T = glutamic acid --> Valine overall = abornal B globin chains HbA is normal = HbS (sickle)
what is the pathophysiology of sickle cells causing problems?
HbS is unstable
they polymerise when deoxygenation
the RBC deform & sickle*
*cold dehydration and dc O2 tension/hypoxia
- Initially this is reversible, but once this happens a few times it is irreversible
this process damages RBC membrane
they adhere to vessel walls & block small vessel causing ISCHAEMIA & INFARCTION
cells are fragile and HAEMOLYSE (breakdown)
What does haemolysis in sickle cell lead to?
release of hb and consumption/release of NO (from vasculopathy and endothelial dysfunction too) leading to functional deficiency of Hb & VASOCONSTRICTION
–> Pulm HTN, priaprism, leg ulcers, cerebrovascular disease (blockage/haem/malformation)
What does infarction from HbSS vaso-occlusion lead to?
infarction of downstream tissues where vaso-occlusion has happened resulting in tissue death and inflammation
- -> acute pain
- -> acute chest syndrome
- -> hyposplenism
- -> osteonecrosis (AVascular)
- -> Nephropathy
What does HbSS mean?
homozygous sickle cell
no normal β-globin
NB: HbA2 and HbF are still produced
What is HbAS (sickle trait carriers) / HbSC (sickle + another point mutation of B-globin genes)?
they are sickle carriers
no disability except hypoxia e.g. know for GA or high altitude
protects against malaria
HbSC = milder form of sickle cell disease
What is HbC?
another point mutation of the β-globin gene
What happens if HbS carrier and B-thalassemia parent have a child?
sickle cell b-thalassaemia
the severity depends on the amount of normal B-chain synthesis
What crises can present at 6 months old?
when HbF concentration is greatly decreased; acute anaemia (sudden drop in Hb) due to:
Haemolytic Crises
Aplastic Crises
equestration
what symptoms do these crises present at 6 months old?
anaemia and jaundice
What is a haemolytic crises (@6m old)?
associated with infection that causes the HbF to be greatly decreased –> acute anaemia
What is the an Aplastic crises (@6m old)?
most often parvovirus B19 as this virus suppresses bone marrow erythropoietic activity –> severe anaemia usually self-limiting <2weeks;
transfusion may be needed
What is a sequestration crises @6m old?
Enlargement of spleen with abdominal pain &
circulatory collapse due to accumulation of cells within the spleen,
(the spleens narrow vessels and functioning in clearing defective TBC renders it very susceptible to microinfarction)
Rx: is supportive with transfusions if required
What happens in painful vaso-occlusive crises?
vaso-occlusion results in ischaemia–> pain;
in bones, abdomen
can occur anywhere in the body though
What happens in a chest crises?
most common cause of mortality in HbSS
vaso-occlusion –> collpase in the lungs,
–>commonest cause of mortality (20%)
pulmonary infiltrates involving complete lung segments
- fat embolism from bone marrow
- or infection with Chlamydia, Mycoplasma or viruses
What happens in a cerebrovascular crisis?
AKA stroke
10% patients suffer strokes during childhood
vaso-occlusion in cerebral circulation; cause of significant mortality & morbidity prevention programme
Why is infection more likely in HbSS?
due to hyposplenism
Risk of overwhelming sepsis more common in childhood
Increased incidence of osteomyelitis due to salmonella etc.
Increased incidence of infection with encapsulated organisms e.g. Strep pneumoniae & HiB
What is the pathophysiology of priaprism in sickle cell?
Persistent and painful erection:
needs urgent treatment since it may lead to fibrosis of the corpus cavernosum with subsequent erectile dysfunction,
- usually nocturnal with risk of long-term impotence
When is splenomegaly common?
in children
What are the long term impact of HbSS on children?
- Short stature & delayed puberty
- Cardiac enlargement & heart failure due to chronic anaemia
- Renal damage
- Adenotonsilar hypertrophy
- Gallstones due to excessive bilirubin production (from heme breakdown/sickle)
- Cognitive problems
- Psychological problem
Why might cognitive problems occur in HbSS?
not only due to strokes but also subtle cerebral damage that occurs
What may adenotonsilar hypertrophy cause?
adenotonsilar hypertrophy –> causing sleep apnoea syndrome leading to nocturnal hypoxaemia which may trigger vaso-occlusive crises
What may renal damage cause in HbSS children?
–> resulting in an inability to concentrate urine –> causing enuresis & dehydration
What are the adult acute crises?
NB: they are similar to paeds ones
- Pain (e.g. bone, often microvascular occlusion of marrow)
- Strokes/seizures/ cognitive defects
- Chest Crisis
- Abdominal Crisis (mesenteric ischaemia)
- Priapism
- Leg ulcers
- Infections
- Hyposplenic
- Osteomyelitis
- Avascular necrosis (articular surface of long bones
What are the chronic complications in adults with HbSS?
- Lungs (hypoxia -> fibrosis -> pulmonary HTN)
- Heart
- Kidneys
- Gallstones
- Retinal disease
- Iron overload or infections from transfusions
Where do vaso-occlusive crises affect infants?
usually in hands and feet
growth plates can be affected!
Where do vaso-occlusive crises affect children?
back, upper and lower extremities
What can trigger vaso-occlusive crises?
hypoxia
infection
cold exposure
What is hand-foot syndrome?
most common complication in HbSS
Swelling of the fingers and feet due to vaso-occlusion; Dactylitis
–> pain due to infarction, necrosis
What are the signs and syx of chest crises?
pleuritic chest pain, SOB, hypoxia, fever, wheeze/cough, tachypnoae - up to 20% mortality
What are the ususal precipitants for a chest crises?
dehydration, infection, cold/damp, unaccustomed exercise, stress, pregnancy, operations
What should you also rule out (DDx) for people coming in with chest crisis?
pneumonia
pneumothorax
PE
How do you investigate a chest crisis?
haemoglobin electrophoresis
- shows HbS, absent HbA, variable HbF
exchange transfusion maybe needed to reduce level of sickle cells <30%
How do you manage a chest crisis?
hospital admission, ANALGESIA A/B - O2, C- IV fluids, antibiotics for infection;
exchange transfusion may be needed to reduce level of sickle cells to <30%
How can you investigate if someone has Hbss?
- can diagnose with new-born screening heel-prick test/ cord blood
Haemoglobin & reticulocytes
Blood film
Sickle solubility test - +ve
Hb electrophoresis or HPLC (high performance liquid chromatography) - will reveal genotype
Bilirubin & LDH - variable; depends on degree of haemolysis
Creatinine - usually below normal limit (lower BP, reduced concentrating ability, increased excretion)
What do haemoglobin and reticulocytes show in HbSS?
Microcytic, hypochromic RBC
Anaemia:
60-90g/l for HbSS,
90-140g/l for HbSC,
Usually reticulocytosis (slightly lower for HbSC than HbSS)
What do you see on blood film in HbSS/HbSC?
sickle cells present, target cells prominent in HbSC
What does a sickle solubility test show?
if have HbS or not
HbS polymerises when you add phosphate buffer + becomes clear - but doesn’t differentiate trait vs HbSS
What Rx can you give to PREVENT a crisis?
folic acid supplements OD to meet the increased demand caused by increased haemolysis
Prompt treatment of infection
Presence of hyposplenism –> BD phenoxymethylpenicillin prophylaxis
Avoid exacerbating factors e.g. cold, excessive exercise, stress
Immunisations are important
Transcranial doppler screening to assess risk of stroke
How do you treat an acute crises?
Quick, adequate analgesia e.g. IV opiates
Regular reviews & pain scores
Bloods:
Crossmatch; FBC, reticulocytes,
blood cultures,
- Measure Packed Cell volume/haematocrit, reticulocytes, liver & spleen size daily
- Blood transfusion if Hb or reticulocytes fall sharply
Urine: MSU +/- CXR if fever or chest signs
Hyper-hydrate with IVI & keep warm
O2 if sats <95%
“Blind” antibiotics e.g. cephalosporin if fever, unwell or chest signs
Exchange transfusion (patient blood is removed & donor blood given in stages - for those rapidly worsening; reduce level of sickle cells to <30%)
What can be given in case of recurrent painful crises if ~6m?
Hydroxyurea
raises HbF level & reduces numbers of crises
What is the Rx (surg and med) can be given in cases of recurrent painful crises (except hydroxyurea)?
Medical:
Transfusion programme
- Regular transfusions +/- Exjade
(iron overload due to repeated transfusions so give with chelating agent)
Surgical:
Bone marrow transplant
What is the prognosis in someone with sickle cell?
- 3% mortality during childhood, mainly due to infection in the first 3 years of life
- Mean survival is 40-50 years of age
