Thalassaemia & SCA Flashcards
Define Thalassaemia
Genetic defect in the protein chains that make up haemoglobin
Defects in alpha-globin chains lead to..
Alpha thalassaemia
Defects in the beta-globin chains lead to..
Beta thalassaemia
Both thalassaemia conditions are autosomal dominant/ recessive
Recessive
Explain the pathophysiology of thalassaemia
The RBCs are more fragile and break down easily, causing haemolytic anaemia. The spleen acts as a sieve, filtering the blood and removing older cells, it collects all the destroyed red blood cells, resulting in splenomegaly
Microcytic anaemia (low mean corpuscular volume)
Thalassaemia
Raised ferritin on Thalassaemia suggests..
Iron overload
Ix for Thalassaemia
FBC
Haemoglobin electrophoresis for globin abnormalities
DNA testing for genetic abnormality
Iron overload may occur in thalassaemia due to..
Increased iron absorption in the gastrointestinal tract
Blood transfusions
Iron overload in thalassaemia can cause symptoms and complications of..
Liver cirrhosis
Hypogonadism
Hypothyroidism
Heart failure
Diabetes
Osteoporosis
For iron overload, serum _____ levels are monitored. Management involves __________ and __________
For iron overload, serum ferritin levels are monitored. Management involves limiting transfusions and iron chelation
The genes that code for alpha-globin are found on chromosome..
16
The severity of symptoms in thalassaemia varies depending on the type and number of genetic defects. What are these?
Carrier
Moderate anaemia (haemoglobin H disease)
Intrauterine death due to severe fetal anaemia (alpha thalassemia major)
Mx for alpha thalassaemia
Monitoring
Blood transfusions
Splenectomy may be performed
Bone marrow transplant can be curative
If 1 or 2 alpha globulin alleles in alpha-thalassaemia are affected then the blood picture would be…
Hypochromic and microcytic, but the Hb level would be typically normal
If there are 3 alpha globulin alleles affected in alpha-thalassaemia it results in..
Hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease
f all 4 alpha globulin alleles are affected in alpha-thalassaemia (i.e. homozygote) then it results in..
Death in utero (hydrops fetalis, Bart’s hydrops)
The gene coding for protein chains in beta-thalassaemia is on chromosome..
11
In beta-thalassaemia, the gene defects can either consist of..
Abnormal copies that retain some function or deletion genes with no function in the beta-globin
Beta-thalassaemia can be split into three types..
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
What is Thalassaemia Minor?
Carriers of an abnormally functioning beta-globin gene. They have one abnormal and one normal gene. Causes mild microcytic anaemia and usually only requires monitoring
What is Thalassaemia Intermedia?
Two abnormal copies of the beta-globin gene. This can be either:
Two defective genes
One defective gene and one deletion gene
Mx for Thalassaemia Intermedia
Significant microcytic anaemia so require monitoring and may need occasional blood transfusions. May require iron chelation to prevent iron overload
What is Thalassaemia Major?
Most severe form. Homozygous for the deletion genes. They have no functioning beta-globin genes
Why does Thalassaemia Major causes fractures?
The bone marrow is under so much strain to produce extra red blood cells to compensate for the chronic anaemia that it expands enough to increase the risk of fractures and change the patient’s appearance
Abnormal features relating to bone changes in Thalassaemia Major include..
Frontal bossing (prominent forehead)
Enlarged maxilla (prominent cheekbones)
Depressed nasal bridge (flat nose)
Protruding upper teeth
Mx for Thalassaemia Major
Repeated transfusions and splenectomy. A bone marrow transplant can be curative
Transfusion can lead to iron overload → organ failure. So iron chelation therapy is important (e.g. desferrioxamine)
Mild hypochromic, microcytic anaemia. It is usually asymptomatic
HbA2 raised (> 3.5%)
Beta thalassaemia trait
What is sickle cell anaemia?
Genetic condition that causes sickle (crescent) shaped red blood cells. This makes it more fragile and easily destroyed leading to haemolytic anaemia
Patients with sickle cell anaemia are prone to..
Various sickle cell crises
Patients with sickle-cell disease have an abnormal variant called..
Haemoglobin S (HbS)
Sickle cell disease is more common in patients from areas traditionally affected by..
Malaria, such as Africa, India, the Middle East and the Caribbean
T or F: Having one copy of the gene (sickle cell trait) reduces the severity of malaria
True - patients with sickle cell trait are more likely to survive malaria and pass on their genes. Therefore, there is a selective advantage to having the sickle cell gene in areas of malaria, making it more common.
Screening for Sca
Newborn blood spot screening test at around five days of age
Pregnant women at high risk of being carriers of the sickle cell gene are offered testing
What is Sickle cell crisis?
Spectrum of acute exacerbations caused by sickle cell disease. These range from mild to life-threatening. They can occur spontaneously or triggered by dehydration, infection, stress or cold weather
Symptoms in homozygotes SCA don’t tend to develop until..
4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin
Some patients inherit one HbS and another abnormal haemoglobin (HbC) resulting in..
Milder form of sickle cell disease (HbSC)
Pathophysiology of SCA
Polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6). This decreases the water solubility of deoxy-Hb
In the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle
Definitive diagnosis of sickle cell disease is by..
Haemoglobin electrophoresis
Long term mx for SCA
Hydroxyurea - increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes
Sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years
Type of sickle cell crises
Thrombotic, ‘vaso-occlusive’, ‘painful crises’
Acute chest syndrome
Anaemic - aplastic, sequestration
Infection
What causes thrombotic crises?
Infection, dehydration, deoxygenation (e.g. high altitude)
Ix for thrombotic crises
Diagnosed clinically
What is acute chest syndrome?
Vaso-occlusion within the pulmonary microvasculature → infarction in the lung parenchyma
Dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, low pO2
Acute chest syndrome
Mx of acute chest syndrome
Pain relief
Respiratory support e.g. oxygen therapy
Antibiotics: infection may precipitate acute chest syndrome and the clinical findings (respiratory symptoms with pulmonary infiltrates) can be difficult to distinguish from pneumonia
Transfusion: improves oxygenation
The most common cause of death after childhood
Acute chest syndrome
What causes aplastic crises?
Caused by infection with parvovirus
Sudden fall in haemoglobin
Aplastic crises
In an aplastic crises, ______________ causes a reduced reticulocyte count
Bone marrow suppression
What is Sequestration crises?
Sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia
Sequestration crises is associated with a decreased/increased reticulocyte count
Increased
Mx for sickle-cell crises
Analgesia e.g. opiates
Rehydrate
Oxygen
Consider antibiotics if evidence of infection
Blood transfusion
When is exchange transfusion indicated in sickle cell crises?
Acute vaso-occlusive crisis (stroke, acute chest syndrome, multiorgan failure, splenic sequestration crisis)
It rapidly reduce the percentage of Hb S containing cells
When is blood perfusion indicated in sickle cell crises?
Severe or symptomatic anaemia, pregnancy, pre-operative
Do not rapidly reduce the percentage of Hb S containing cells
exchange transfusion
Pain and swelling in the hands or feet but can affect the chest, back, or other body areas. It can be associated with fever
It can cause priapism in men by trapping blood in the penis, causing a painful and persistent erection
Vaso-occlusive Crisis
Hypovolaemic shock occurs secondary to which type of SCA crises?
Splenic Sequestration Crisis
A vaso-occlusive crisis, fat embolism or infection can trigger..
Acute Chest Syndrome
Which medications are used in Acute Chest Syndrome?
Hydroxycarbamide (stimulates HbF)
Crizanlizumab (targets P-selectin)
T or F: In alpha thalassaemia, α chains are present in HbA, HbA2
and HbF therefore all are affected
True
Excess β chains form tetramers (β4) called..
HbH
One or two alpha genes missing
α thalassaemia trait
Only one alpha gene left
HbH disease
No functional α genes
Hb Barts hydrops fetalis
β+/β or β0/β
β thalassaemia trait
β+/β+ or β0/β+
β thalassaemia intermedia
β0/β0
β thalassaemia major
β thalassaemia major leads to Extramedullary haematopoiesis which can cause..
Cord compression
Mx of iron overload
Iron chelating drugs (eg desferrioxamine)
Hb→ HbS (α2βs2)
Sickling disorder
β/βs
Sick cell trait
βs/βs
SCA
Chronic haemolysis + hyposplenism
SCA
