Haemoglobinopathies Flashcards
Which type of haemoglobin is predominant in adults and what are its components?
HbA –> 2 alpha + 2 beta chains
What is HbA2 composed of?
2 alpha + 2 delta chains
What is HbF and what is it composed of?
Foetal Hb –> 2 alpha + 2 gamma chains
When will a child usually reach adult levels of HbA?
Age 6-12 months (so beta chain problems wont manifest until then)
What are haemoglobinopathies?
Hereditary, autosomal recessive conditions
Affecting globin chain synthesis
What are the two main groups of haemoglobinopathies?
Thalassaemias (decreased rate of globin synthesis)
Structural Hb variants (normal production of abnormal globin chain e.g. HbS)
What are the two main types of thalassaemia?
Alpha thalassaemia
Beta thalassaemia
Describe the different severities of alpha thalassaemia
Alpha chain has 2 genes, so 4 alleles:
- 1 allele affected = silent carrier
- 2 alleles affected = trait
- 3 alleles affected = HbH disease
- 4 alleles affected = Hb Barts
Describe the different severities of beta thalassaemia
Beta chain has 1 gene, so 2 alleles:
- 1 allele affected = trait
- 2 partially functioning alleles = thalassaemia intermedia
- 2 non-functioning alleles = thalassaemia major
What are the features of Hb Bart?
Causes intrauterine haemolytic anaemia + hydrops fetalis –> usually fatal
In which geographical areas is alpha thalassaemia most common?
SE Asia
Africa
India
In which geographical areas in beta thalassaemia most common?
Mediterranean
Middle East
Central/South Asia
China
Which signs/symptoms are seen in both alpha and beta thalassaemia?
Haemolytic anaemia:
- SOB
- fatigue
- pallor
- murmur from increased CO
- splenomegaly +/- hepatomegaly
- failure to thrive, reduced growth
Which additional features might be seen in beta thalassaemia?
Jaundice Facial dysmorphia: - frontal bossing - maxillary hypertrophy - large head Osteopenia
Which sign might be the only feature in thalassaemia trait/minor?
Microcytic anaemia
How is thalassaemia diagnosed?
Hb electrophoresis or chromatography
Which electrophoresis finding is characteristic of beta thalassaemia trait?
Increased HbA2
What would be seen on electrophoresis in beta thalassaemia major?
Mainly HbF, no HbA
What would be seen on electrophoresis in HbH disease?
HbH –> excess beta chains form B4 tetramers (HbH)
What is the management for beta thalassaemia intermedia and HbH disease?
Occasional transfusions
What is the management for beta thalassaemia major?
Lifelong regular transfusions
–> maintain Hb 95-105
What is the main cause of mortality in beta thalassaemia major?
Iron overload from regular transfusions
How is iron overload managed in thalassaemia?
Iron chelating drugs e.g. desferrioxamine (SC/IV)
venesection not possible as patient is already anaemic
Which side effects of iron chelating drugs is it important to monitor closely for?
Hearing and vision loss
What is the pathophysiology behind ‘sickling’?
Recessive mutation in gene for beta-globin –> HbS (altered structure)
HbS polymerises if exposed to low oxygen levels for a prolonged period –> distorted shape of red cell
What are the consequences of HbS red cells?
Breakdown easily –> haemolytic anaemia
Occlude the microvasculature
Are sequestered in liver + spleen –> splenic dysfunction + immunosuppression
What is the lifespan of a HbS red cell?
20 days (HbA is 120 days)
What are the features of sickle cell trait?
Asymptomatic carrier
May sickle in severe hypoxia e.g. high altitude, under anaesthesia
What would be seen on the blood film and electrophoresis in sickle cell trait?
Film normal
Mainly HbA, HbS < 50%
Which parts of the world have the highest rates of sickle cell anaemia?
Afro-Caribbean
Middle East
Mediterranean
Indian
How would sickle cell anaemia appear of electrophoresis?
HbS > 80%, no HbA
What are the chronic features of sickle cell anaemia?
Haemolytic anaemia: pallor, fatigue, jaundice
Chronic pain
Painful dactylitis (in age 6-18 months)
Splenomegaly
Hyposplenism due to repeated infarcts
Pigment gallstones from chronic haemolysis (affects 70%)
Raised CO –> systolic murmur + cardiomegaly
What is a sickle cell crisis?
Episode of tissue infarction due to vascular occlusion
What might trigger a sickly cell crisis?
Cold Dehydration Stress Infection Pregnancy Acidosis Hypoxia
Give some examples of symptoms of sickle cell crisis?
Acute painful limb, abdomen or chest
Stroke
Visual floaters
Chest pain + pneumonia –> acute chest syndrome (common in kids)
Which type of infection may precipitate an aplastic crisis in a patient with sickle cell anaemia?
Parovirus B19
Which type of infections are sickle cell patients particularly susceptible to?
Encapsulated bacteria –> due to hyposplenism (spleen responsible for removing encapsulated bacteria)
How is sickle cell disease diagnosed?
Electrophoresis
High performance liquid chromatography (HPLC)
Hb isoelectric focusing (IEF)
What is the general management of sickle cell anaemia?
Avoid alcohol + smoking
Prophylactic penicillin + all vaccinations
Folic acid supplements (especially in pregnancy)
Transfusions if symptomatic anaemia
Splenectomy if 2 sequestration crises
Hydroxycarbamide can reduce severity by inducing HbF production
How is a sickle cell crisis treated?
Opiates Hydration Rest Oxygen Antibiotics if infection Red cell exchange transfusion if chest crisis or stroke
How are haemoglobinopathies screened for?
Antenatal screening to identify carriers
- family origin questionaire + FBC
- further testing if from high risk area or abnormal red cell indices
