Thalassaemias Flashcards
Define Thalassaemias
Autosomal recessive inherited disorders of haemoglobin, causing reduced globin chain synthesis, resulting in impaired haemoglobin production
What is the cause of autosomal recessive inherited disorders of hemoglobin, leading to reduced globin chain synthesis?
Genetic defects in the alpha-globin or beta-globin chains result in impaired hemoglobin production
What are the causes of alpha thalassemia?
Defects in the alpha-globin chains, which can result from the deletion of one or both alpha-globin genes on chromosome 16
What are the clinical features of the alpha thalassemia trait?
Asymptomatic carrier state with microcytic hypochromic red cells and mild anaemia.
Ferritin levels are normal, and no treatment is needed
What is HbH disease in alpha thalassemia?
It occurs when only one alpha gene is left.
It leads to moderate to severe anaemia with very low MCV and MCH.
Excess beta chains form tetramers called HbH
What is Hb Barts hydrops fetalis and what is its consequences?
A severe form of alpha thalassemia where no functional alpha genes are present, leading to fetal death.
It causes severe hypoxia, growth retardation, and cardiac failure
What causes beta thalassemia?
Mutations affecting the beta-globin chain synthesis, often caused by point mutations on chromosome 11, leading to reduced or absent beta chain production
What is the difference between beta thalassemia trait and beta-thalassemia major?
Beta thalassemia trait
= Asymptomatic with mild anaemia, low MCV/MCH, and raised HbA2 levels.
Beta thalassemia major
= Severe anaemia requiring lifelong transfusions presents with pallor, failure to thrive, hepatosplenomegaly, and skeletal changes. Elevated ferritin levels
What is the clinical presentation of beta thalassemia major?
(1) Presents early (6-24 months) with severe anaemia
(2) pallor
(3) hepatosplenomegaly
(4) skeletal abnormalities
(5) extramedullary hematopoiesis.
= production of blood cells outside the bone marrow, often in the spleen or liver
Hb analysis shows mainly HbF with no HbA
What investigations are used to diagnose thalassemia?
(1) FBC →
Shows microcytic anaemia with decreased Hb, MCV, and MCH.
(2) HPLC or electrophoresis →
Elevated HbA2 is diagnostic of beta thalassemia trait.
(3) DNA testing →
Identifies the genetic abnormality
How is thalassemia major managed?
(1) Lifelong blood transfusions to maintain haemoglobin levels (95-105 g/L)
(2) Suppress ineffective erythropoiesis and prevent iron overload.
(3) Bone marrow transplant may be considered before complications
What are the complications of thalassemia, especially related to iron overload?
(1) Endocrine dysfunction
(2) Cardiac disease (e.g., cardiomyopathy)
(3) Liver disease (e.g., cirrhosis)
(4) Growth retardation.
What is used to manage excess iron?
Iron chelation therapy
= desferrioxamine
A 72-year-old gentleman attends his GP for blood as part of a ‘well man’ check-up. The blood demonstrates an Hb of 8.4, MCV of 66, WCC of 8.7, Platelets of 320 and an otherwise unremarkable full blood count. Iron studies are entirely normal.
The patient denies any overt blood loss, tiredness, weight loss or change to his bowel habits. He drinks 4 units of alcohol per week and is a non-smoker. Pending further investigation, what is the most likely cause?
Thalassaemia trait
what does elevated HbA2 mean
key diagnostic marker for beta thalassemia trait
How does elevated HbA2 come around?
(1) Beta thalassemia trait leads to a reduced production of beta chains.
(2) As a compensatory mechanism, the body increases the production of delta chains
(3) Which is combined with alpha chains to form HbA2.
(4) This results in an elevated level of HbA2, typically greater than 3.5% (normal is 2-3%)
When does the transition from HbF (fetal haemoglobin) to HbA (adult haemoglobin) occur?
The transition occurs within the first few months of infancy
What causes haemoglobinopathies?
mutations affecting globin chain production
What is the inheritance pattern of haemoglobinopathies?
Autosomal recessive manner, with carriers being unaffected
What are thalassaemias, and how do they affect globin chain synthesis?
Thalassaemias are conditions characterised by a decreased rate of globin chain synthesis
When should you suspect thalassaemia?
if a patient has microcytic hypochromic anaemia with normal ferritin levels.
What clinical features will be found on examination of a patient with thalassaemia?
(1) Younger than the age of 2
(2) More commonly those of Mediterranean origin
(3) Microcytic anaemia
(4) Failure to thrive
(5) Hepatosplenomegaly
What do iron studies show in the case of thalassaemia?
Increased serum iron and increased iron binding capacity
What is the mode of inheritance of Thalassemia?
Autosomal Recessive
A microcytic anaemia with a low mean cell volume in the absence of other symptoms particularly in individuals of Mediterranean origin may suggest what?
Thalassemia traits
Repeated blood transfusions (for example for beta thalassaemia patients) can lead to what happening?
Iron overload which can cause joint pain and hyperpigmentation of the palmar crease
Jaundice
Fatigue
Facial bone deformities
What do these symptoms suggest?
Patient has beta or Alpha-thalassaemia. Mainly beta
Those with beta-thalassaemia major should have regular ? blood transfusions of packed red blood cells for the rest of their life
2-4 weeks
A 2-year-old Turkish boy presents to his GP. His parents say that he has not been himself. In particular, he seems less fit than his peers and appears pale. His height and weight are much lower than expected. On examination, he has signs of an enlarged liver and spleen. His parents state that his cousin has experienced similar symptoms. His birth was at term and there were no complications. His immunisations are up to date.
What investigation will confirm the diagnosis? and what will it show?
Haemoglobin electrophoresis
= an increase in HbF or HbA2
A G1P0, 23-year-old woman, who is 10+1 weeks pregnant, attends her obstetrician for the results of her recent blood tests. Her recent blood test confirms a diagnosis of alpha (α) thalassaemia minor. She is concerned about how this diagnosis may affect her baby.
What foetal complication is associated with α-thalassaemia?
Bart’s hydrops fetalis
A 20-year-old male presents with microcytic hypochromic anaemia and an elevated haemoglobin A2 level on electrophoresis. What is the likely diagnosis?
Beta-thalassemia trait
A 20-year-old male presents with microcytic hypochromic anaemia and a decrease in alpha-globin production which does not cause an elevated haemoglobin A2 level. What is the likely diagnosis?
Alpha-thalassemia trait
“All four beta globin genes are damaged or missing”
alpha thalassaemia major
“Two damaged or missing genes for beta-globin”
beta thalassaemia major
A 35-year-old woman with beta-thalassemia major comes into the emergency department complaining of bruising on her legs. She is otherwise well.
On examination, she has multiple reddish/brown macules over her legs.
What is the most likely diagnosis?
Haemosiderosis
= transfusion-induced
HbA2 is a form of haemoglobin made up of what?
2 alpha and 2 delta chains
What is the inheritance and presentation of alpha-thalassemia trait?
Inheritance
= One defective alpha-globin gene (heterozygous).
Presentation
= Mild microcytic hypochromic anaemia, usually asymptomatic or mild symptoms.
Labs
= Normal or slightly low MCV/MCH, normal HbA2 levels
What is the inheritance and presentation of alpha-thalassemia major?
Inheritance
= Three or four defective alpha-globin genes (homozygous or compound heterozygous)
Presentation
= Severe anaemia from birth, hydrops fetalis, jaundice, splenomegaly, failure to thrive, and cardiac failure.
Labs
= Hb Bart’s and Hb H. Fatal without treatment.
What is the inheritance and presentation of beta-thalassemia trait?
Inheritance
= One defective beta-globin gene (heterozygous).
Presentation
= Mild microcytic anaemia, often asymptomatic.
Labs
= Elevated HbA2 levels (>3.5%).
What is the inheritance and presentation of beta-thalassemia major?
Inheritance
= Two defective beta-globin genes (homozygous or compound heterozygous)
Presentation
= Severe anaemia, failure to thrive, splenomegaly, hepatomegaly, bone deformities, and jaundice.
Labs
= Very low HbA, elevated HbF and HbA2
