Thalassaemia, Sickle Syndromes and Haemolytic Anaemia Flashcards
How do Thalassaemias cause a reduced Hb production?
by causing a reduced globin chain synthesis.
What type of Inheritance pattern do Thalassaemias exhibit?
Autosomal recessive
In which Geographical Populations are Thalassaemias more prevalent?
Mediterranean Europe
Central Africa
Middle East
Indian Subcontinent
South East Asia
Having Thalassaemia trait is believed to confer some protection against which disease?
Falciparum Malaria
What Arrangement of Globin chains make up Haemoglobin usually?
2 Alpha and 2 beta chains.
What is the most prevalent Major form of Haemoglobin in adults?
HbA - 97.5%
HbA2 - 2.5%
What Types of Chains make up the different Major Haemoglobin forms?
HbA - 2 alpha 2 Beta
HbA2 - 2 Alpha 2 delta
HbF - 2 Alpha 2 Gamma
What type of Anaemia do Thalassaemia’s result in?
Inadequate Haemoglobin production = “Microcytic Hypochromic Anaemia”.
How many Alpha genes would an unaffected individual have?
4 genes from Chromosome 16
How many Alpha Genes would an individual with Alpha Thalassaemia trait have?
One or two alpha genes missing, no medical treatment needed.
- Mild hypochromic red cells with mild anaemia.
(Important to distinguish from iron deficiency anaemia - Ferritin will be normal)
How many Alpha genes would a patient with HbH disease have?
Only has one alpha gene remaining (3 defective copies).
- Moderate to severe anaemia with very low MCV and MCH.
- Excess Beta chains form tetrameres (β4) called HbH.
- Common in SE asia.
How many Alpha genes would a patient with Hb Barts hydrops fetalis have?
No Functional Alpha genes.
incompatable with life.
- No Alpha chains to bind to so tetramers of Hb Barts (gamma 4) and HbH (β4) produced.
What are some of the clinical features of Alpha Thalassaemia?
- Jaundice
- Facial Bone deformities
- fatigue
- Hb Barts hydrops fetalis:
- Profound anaemia
- Cardiac failure
- Growth retardation
- Severe hepatosplenomegaly
- Skeletal and cardiovascular abnormalities
- Almost all die in utero
What would High Performance Liquid Chromatography (HPLC) or Electrophoresis show in Alpha Thalassaemia?
Can be normal (Because Alpha genes affect all the Heam groups), so DNA analysis is required to make the diagnosis.
When are pregnant women offered screening for thalassaemia in the UK?
At booking
What type of mutations predispose to Beta Thalassaemia?
Point mutations on chromosome 11.
Which major types of Haemoglobin are affected in Beta Thalassaemias?
Only HbA1 (adult Haemogobin) because it is the only one in which Beta globin chains are involved.
What does “β+” mean in terms of the number of beta genes?
Reduced by one.
SO β+/β would be 3 genes working and one defective/missing.
What does “β0” mean in terms of the number of beta genes?
That the Gene is absent entirely. so only one copy left (on the other chromosome)
SO β0/β would only have 2 genes left.
WHat clinical features are seen in β thalassaemia trait (β+/β or β0/β)?
Asymptomatic.
- Mild / No Anaemia
- Low MCV / MCH
- Raised HbA2 (DIAGNOSTIC)
What clinical features are seen in β thalasseamia major (β0/β0)?
Severe symptomatic anaemia at 3-9 months of age
- Becomes evident when HbF levels fall, and HbA levels are meant to take over.
- Failure to thrive
- frontal bossing (protrusion of Frontal bone)
- Maxilliary overgrowth.
- hepatosplenomegaly due to extramedullary haematopoiesis.
What features are seen in β thalassaemia intermedia (β+/β+ or β0/β+)?
Moderate severity requiring occasional transfusion.
How is Beta Thalassaemia minor trait investigated?
High-performance liquid chromatography (HPLC) or electrophoresis: increased HbA2 is diagnostic!
What are some complication of extramedullary haematopoiesis?
Causes cord compression.
Refers to the production of HbF by tissues such as liver, and other organs (as well as spinal cord)
Would β-thalassaemia intermedia have an isolated microcytosis and mild anaemia? or an isolated Macrocytosis and No anaemia?
Mild microcytosis and Anaemia.
which type of Thalassaemia is splenectomy indicated in?
HbH thalassaemia (alpha)
In patients with more severe thalassaemias, what is the mainstay of Tx?
Lifelong blood transfusions to keep Hb at 95 - 105g/l.
- Suppresses ineffective erythropoiesis
- inhibits over-absorption of iron.
- Allows for normal growth and development.
What is a complication of Thalassaemia Tx?
Iron overload from transfusion is the main cause of mortality.
- Half of patients with β-Thal major die before the age of 35 yrs, usually from cardiac failure secondary to iron overload.
Target cells can be seen in which thalassaemia disease?
Beta Thalassaemia’s
