Thalassaemia Flashcards
What is Thalassaemia
autosomal recessive haemoglobinopathy which causes a microcytic anaemia.
Blood counts for alpha thalassaemia
HbA (A2 B2) Reduced
HbA2 ( A2 G2) Reduced
HbF (A2 Y2) Reduced
Beta thalassaemia
HbA (A2 B2) Reduced
HbA2 ( A2 G2) Increased
HbF (A2 Y2) Increased
Epidemiology of thalassaemia
- Thalassaemia is prevalent in areas with malaria as there is evidence to suggest that thalassaemic red cells provide immunity against the parasite.
- Alpha thalassaemia: Asian and African descent
- Beta thalassaemia: South-East Asian, Mediterranean, and Middle Eastern descent
Life expectancy of beta thalassaemia
Alpha and beta have normal life expectancy
Beta thalassaemia major is fatal in the first few years of lifeif untreated, and the leading cause of death is heart failure.
What is Alpha-thalassemia
genetic disorder where there’s a deficiency in production of the alpha globin chains of haemoglobin.
autosomal recessive condition
Epidemiology of alpha thalassaemia
Common in individuals of Asian and African descent
Risk factors for alpha thalassaemia
Family history
Why does alpha thalassaemia occur?
occurs due to impaired synthesis of α-globin due to genetic deletions.
Alpha thalassaemia trait:
people with 2 gene deletions: mildly anaemic with near-normal haemoglobin electrophoresis
either be caused by:
‘cis’ deletion: mutated genes are on the same chromosome
‘trans’ deletion: mutated genes are on two different chromosomes.
HbH alpha thalassaemia:
- people with 3 gene deletions
- unable to form alpha chains.
- The beta chains form tetramers (HbH) > damage erythrocytes causing moderate to severe disease
- HbH cause damage by causing haemolysis as well as having a high affinity for O2 and not releasing O2 to tissues.
Hb barts (alpha thalassaemia major)
- people with 4 gene deletions
- die in uterobecause the gamma chains form tetramers (Hb Barts)
- cannot carry oxygen efficiently
- Severe hypoxia leads to high-output cardiac failure and massive hepatosplenomegaly > resulting in oedema all over the body, called hydrops fetalis.
WHat is a consequence of hypoxia?
signals the bone marrow, liver andspleen to increase production of RBCs.
This may causebones containing bone marrow, as well as the liver andspleen, to enlarge.
Signs of alpha thalassaemia
Usually asymptomatic
- Pallor: due to anaemia
- Jaundice: due to unconjugated bilirubin
- Chipmunk facies: compensatory extramedullary hematopoiesis in the skull causes marrow expansion
- Hepatosplenomegaly
- Failure to thrive
Symptoms of alpha thalassaemia
- Shortness of breath: due to anaemia
- Palpitations: due to anaemia
- Fatigue: due to anaemia
- Swollen abdomen: due to hepatosplenomegaly
Investigations for alpha thalassaemia
FBC
Blood film
Hb electrophoresis
DNA testing
Management of alpha thalassaemia
Regular Blood transfusion: Dependent on Hb level
Iron chelation
Folate supplementaion
Splenectomy
Stem cell transplantation
Complications of thalassaemia
HF
Hypersplenism
Aplastic crisis
Iron overload
Pericarditis
Arrhythmias
Gallstones
What is beta thalassaemia
Beta thalassaemia is a genetic disorder where there’s a deficiency in the production of the β-globin chains of haemoglobin.
It is an autosomal recessive condition.
Epidemiology of beta thalassaemia
Most commonly seen in Mediterranean, African and South East Asian populations.
RF is family history
What happens in beta thalassaemia
partial or complete β-globin chain deficiency, due to a point mutation in the beta globin gene present on chromosome 11.
result is either a reduced, or completely absent beta globin chain synthesis.
3 possible phenotypes of beta thalassaemia
Beta thalassaemia trait -Normal and reduced beta chain
Beta thalassaemia intermedia - Reduced beta chain/ reduced beta chain or reduced beta chain/absent beta chain
Beta thalassaemia major: absent beta chain/ absent beta chain
What happens when there beta globin chain deficiency
- Free α-chains accumulate within red blood cells
- clump together to form intracellular inclusions
- Which damage the red blood cell’s cell membrane, causing haemolysis
causes haemoglobin to spill out of RBCs. Haemoglobin can then be recycled into iron and unconjugated bilirubin.
Excess unconjugated biliruin and excess iron leads to
Jaundice
Secondary hemochromatosis
What can haemolysis lead to
Hypoxia
What age does major beta thalassaemia present
< 2 years old
Signs of beta thalassaemia
Usually asymptomatic
- Jaundice: due to unconjugated bilirubin
- Pallor: due to anaemia
- Hepatosplenomegaly
- Chipmunk facies: enlarged forehead and cheekbones
- Failure to thrive
Symptoms of beta thalassaemia
- Shortness of breath: due to anaemia
- Palpitations: due to anaemia
- Fatigue: due to anaemia
- Swollen abdomen: due to hepatosplenomegaly
- ## Growth retardation
1st line investigation for beta thalassaemia
FBC
Bood film
Hb electrophoresis
Skull x ray
DNA testing
Management of beta thalassaemia
Doesnt usually require treatment
Other than that same as aloha
Complications of beta
HF
Hypersplenism
Aplastic crisis
Iron overload
Gallstones
