Sickle cell disease Flashcards
Why is sickle cell disease still present
Sickle cell trait provides protection against malaria in endemic areas, Sickle cell disease doesnt but occurs when inherit two faulty genes
What mutation causes sickle cell
Beta chain - glutamic acid replaced with valine (less polar)
Why does deoxygenation of RBC matter in sickle cell
When deoxygenated, confirmation exposes mutation -> less oluble and allows polymerisation -> vasoocclusion
What does polymerisation of RBC in sickle cell cause
Ischaemia and necrosis #Haemolysis of damaged RBC
Risk factors for sickle cell crisis
-Anything that shifts oxygen dissociation curve to the right - deoxy Hb
Hypoxia
Fever
Acidosis
Increased temp
Infection
Dehydration
-Anything -> vasoconstriction
Cold
Pain
Menstrual periods
Alcohol
Dehydration
What causes tissue damage in sickle cell
Ischaemia -> necorsis
Neurotrasnmitters and other mediators eg nociceptors
Intravascular haemolysis (RBC contents -> bloodstream)
Symptoms of sickle cell
PAIN - constant or intermittent
Sickle cell cirsis
Hyposlpenism -> increased risk of infections
Complications of sickle cell
Stroke
Renal disease, chronic HPTN
Priapism
Hyposplenism
Lung disease
Retinopathy
Fatigue
Miscarriage
AVN - bones??
Current life expectancy mid 60s
Treatment of sickle cell
Treat comlpications
Treat sickle crisis
Monitor and treat chronic complications -
-penicillin prophylaxis infection
Imunisations
Contol BP
Monitor pregnancies
Retinopathy screening
Hydrocycarbamide
How to reduce crisis in sickle cell
Hydroxyccarbamide
Regular transfusions
Bone marrow transplant - only cure
How does hydroxycarbamide work
Increases gamma chain production -> increased foetal haemoglobin
How does transfusion work in sickle cell? Complications?
Reduce sickle Hb in blood, less frequent crisis, doesnt stop haemolysis
Can cause iron overload AB formation
Bone marow transplant to treat sickle cell risk
Can cure but very high risk
Morality and morbidity high not always successful
V selective with who receives
New treatments for sickle cell
Gene therapy
Voxelotor - inhibit HbS polymerisation
Crizanilzumab - anti P selectin
Where is commonly affected in sickle cell crisis
Back, chest, extremeties
Sickle cell crisis symptoms
Pain
Mild fever, swelling of bones and joints
2-7 days
What prophylaxis is given to all sickle cell crisis
DVT
What investigation use to prevent progression to acute chest syndrome
Incentive spirometry
What occurs in sickle trait and hwy
Mild haemolysis
Protective against malaria
Disease = RBC reduced lifespan massively and splenic dysfunction
What does beta mutation cause in sickle cell
(glutamic acid replaced with valine in chain - valine less polar -> less soluble and polymerisation Hb
Predisposing factors to sickle cell crisis
Anything shifting oxygen dissociation curve - deoxygenating RBCs
-hypoxia, fever, acidosis, increased temp, infection, dehydration
Anything -> casoconstriction
Cold, pain, dehydration
Cycle of sickle cell
Vasoconstriction -> worsening vasocculsion and tissue hypoxia
Vasoocclusion -> tissue hypoxia and pain
Tissue hypoxia -> sickling -> haemolysis
What to do sickle crisis first aid
- Treat pain - escalate painkiller quickly, patient controlled useful
- Hydrate - oral or IV
- Keep warm
- Treat infection
- Consider oxygen if hypoxic (otherwise unhelpful)
- Consider transfusion - haemotology
- Consider secondary effects
- Chest crisis - sickling lungs -. hypoxia, high mortality
- Priapism
- Stroke - thrombolysis
What to monitor in sickle cell
Penicillin prophylaxis
Immunisations for hyposplenism
Control BP
Monitoring in oregnancy
Retinopathy screening
How does hydroxycarbamide work
Increasing haema/gamma Hb (foetal) eg normal
Reducing number of crisiss
Hydroxycarbamide
Regular blood transfusions in some patinet
Bone marrow transplant curative but c high risk
Oxelotor
Crianlizumab
Gene therapy
How does oxelotor and crizanlizumab work
Oxelotor - inhibit HbS polymerisation
Crizanlizumab - antiP selecion
Complications of regular blood transfusions
Iron overloard, AB formation
Diagnosis of sickle cell
Hb electrophoresisi
Priapism what is it
Painful penile erection secondary to venous obstruction otuflow from corpus cavernosum
INfe tions more likely in sickle cell
Strep pneumoniae, h influenzaen
ocular comps sickle cell
Retinopathy
Vitreous haemorrhage
Retinal detatchement
What can parvovirus B19 cause in sickle cell
Aplastic crisis - temproaraily halts production RBC
Acute chest syndrome symptoms
Fever, chest pain, cough, SOB, hypoxia
When does sickling crisis occur HbAS vs HbSS
HbAS - 2.5-4 pO2 kpa
HbSS - 5-6 pO2 Kpa
Inheritance sickle cell
Autosomal recessive
How often give pneumococcal vaccine in sicke cell
every 5 years
