Sickle cell anaemia Flashcards
Explain the genetic changes occuring in Sickle cell disease
Missense mutation in ß-globin gene that exchanges Glutamic acid for Valine
–> Valine is non-polar –> makes it insoluble and induces changes in Hb form
What are the changes in a sickle cell patient in comparison to a healthy individual to the erythrocytes
Changes come in stages
Stages in sickling of red cells
- Distortion –> Rigidity (steif)
- Polymerisation initially reversible with formation of oxyHbS
- Subsequently irreversible
- Dehydration
- Increased adherence to vascular endothelium
Also:HbS has a low affinity for O2–> decreased erythropoietic drive
What is sickle cell anaemia?
The homozygous disease of HbS (both ß-globin genes are affected)
What is sickle cell trait?
The heterozygous sickle cell disease (HbAS) –> only one ß globin chain is affected
What is sickle cell disorder?
Sickle cell Anaemia (HbSS) and Sickle cell traid (HbAS) together +
incorporates sickle cell anaemia and all other conditions that can lead to a disease syndrome due to sickling
Explain the clinical features of sickle cell anaemia
(clinical non-haematological signs)
- Shortened red cell lifespan due to increased haemolysis leading to
- Anaemia
- Gall Stones (high levels of Bilirubin)
- Aplastic Crisis (Parvovirus B19) (targets immature Erythrocytes)
2. Anaemia partly due to a reduced erythropoieticdrive as haemoglobin S is a low affinity haemoglobin
- Blockage to microvascular circulation (vaso-occlusion –> because regidity + adherence) leading to:
- Tissue damage and necrosis (Infarction)
- Pain
- Dysfunction
One of the complications for Sickle cell anaemia is tissue infarction
What might this lead to?
- Spleen
- hyposplenism –> more prone to infection
- Bones/Joints
- dactylitis
- avascular necrosis
- osteomyelitis
- Skin
- chronic/recurrent leg ulcers
What is dactylitis?
Severe inflammation of finger and toe (joints)
–> can be due to tissue infarction in the joints in Sickle cell desease and might be very paiful (normally presents within first years of life in sickle-cell)
Explain the pathogenesis of vaso-occlustion in sickle cell disease
Polymersation of Hb leads to distortion of erythrocyte which leads to increased endothelial adherence
+
Cell-free haemoglobin limits nitric oxide bioavailability in sickle cell disease
Explain the relationship between sickle cell disease and pulmonary hypertension
The likely mechanism is that the free plasma haemoglobin resulting from intravascular haemolysis scavenges NO and causes vasoconstriction
–> poor prognosis and correlated with severity of haemolysis
Which complications might occur in sickle-cell disease in following tissues/organs
Lung
urinary tract
brain
eyes
Lungs
- Acute chest syndrome
- Chronic damage
- Pulmonary hypertension
Urinary tract
- Haematuria (papillary necrosis)
- Impaired concentration of urine (hyposthenuria)
- Renal failure
- Priapism (prolonged errection, can be without stimmulation)
Brain
- Stroke (mainly in large (e.g. middle cerebral) arteries leading to
- Cognitive impairment
Eyes
- Proliferative retinopathy (like in diabetis)
When and how is the typical fist presentation of a patient with sickle-cell anaemia?
Usually wihthin the first 3-6 Months
- Dactylitis
- Splenic sequestration* –> spleen pools blood volume, goes together with splenic enlargements
- Infection-S. pneumoniae*
–> last two can be fatal!
Which clinical emergencies might occur in someone with sickle cell anaemia?
- Infections leading to Septic shock (BP <90/60)
- Stroke leadint to Neurological signs or symptoms, most commonly in children
Acute Chest syndrome:
New pulmonary infiltrate on chest X-ray with Fever, Cough, Chest pain, Tachypnoea
- SpO2 <92% on air –> deoxygenation might lead to further formation of sickle-shape
- Symptoms/signs of anaemia with Hb <5 or fall >3g/dl from baseline
- Priapism >4 hours
Avascular Necrosis of the Femoral Head
What are the laboratory / haematological features of someone with sickle cell disease
- Hb low (typically 6-8 g/dl)
- Reticulocytes high–> to compensate (except in aplastic crisis)
- Film
- Sickled cells
- Boat cells
- Target cells
- Howell Jolly bodies
How do you diagnose Sickle-cell anaemia?
Definate diagnosis
- Electrophoresis
- Chromatography (HPLC)
But also:
Solubility test might give you an indication for it (but no definate diagnosis)
