Thalassaemia Flashcards
What are thalassaemias?
Thalassaemias are hereditary conditions in which there is reduced globin chain synthesis resulting in impaired haemoglobin production
What are the 2 main types of thalassaemia?
- Alpha thalassaemias - Alpha chains affected
- Beta thalassaemias - Beta chains affected
How can thalassaemia lead to anaemia?
Inadequate haemoglobin production leads to production of smaller red blood cells, causing a microcytic, hypochromic anaemia
Describe the epidemiology of thalassaemia
These are the most common monogenic disorders and is a major cause of morbidity worldwide
This is much more commonly found in hotter climates such as southern asia and northern africa (May be protective against malaria)
What are some possible complications of severe thalassaemia?
If severe, it can cause unbalanced accumulation of globin chains which are toxic to the cell, as well as ineffective erythropoiesis and haemolysis
What is alpha thalassaemia?
Alpha thalassaemia is a form of thalassaemia in which alpha chain synthesis is affected
What symbol is given to a chromosome containing 1 functional alpha gene and 1 missing alpha gene?
α+
What symbol is given to a chromosome containing 2 missing alpha genes?
αº
What are the 4 main classes of alpha thalassaemia?
- Silent α-thalassaemia
- Thalassaemia trait
- Haemoglobin H (HbH) disease
- Haemoglobin Barts Hydrops Fetalis
What is the genetic makeup of a person with silent α-thalassaemia?
(α α+)
How will silent α-thalassaemia present?
This will cause no symptoms, however, it makes the person a carrier, meaning they may pass it onto their offspring
What are the possible genetic makeups of thalassaemia trait?
(α+ α+) or (α αº)
How will thalassaemia trait present?
This is also an asymptomatic carrier state, but can cause microcytic hypochromic red cells
Ferritin will, however, be normal
What is the genetic makeup of haemoglobin H (HbH) disease?
(α+ αº)
How will haemoglobin H disease present?
This will cause moderate to severe anaemia due to the lack of alpha chains, so normal adult haemoglobin (HbA) cannot form
Excess ß-chains therefore form tetramers (ß4) called HbH
This can lead to jaundice, splenomegaly and may require regular transfusions
What is the genetic makeup of haemoglobin barts hydros fetalis?
(αº αº)
Describe the pathology of Hb barts hydrops fetalis?
This is a defect that is incompatable with life as there are no remaining alpha genes to make haemoglobin
As in HbH, disease, tetramers of Hb Barts (γ4) or HbH (ß4) produced
What are some clinical features of haemoglobin parts hydrops fetalis?
- Profound anaemia
- Cardiac failure
- Growth retardation
- Severe hepatoplenomegaly
- Skeletal and cardiovascular abnormalities
- Almost all die in utero unless transfused in utero (Usually avoided)
How is risk of Hb Barts hydrops fetalis decreased?
Antenatal screening is performed
What is ß-thalassaemia?
Beta thalassaemia is a form of thalassaemia in which beta chain synthesis is affected
What symbol is given to a ß gene with reduced activity?
ß+
What symbol is given to a ß gene with absent activity?
ߺ
What type of haemoglobin is affected in ß-thalassaemia?
HbA as this is the only form containing ß chains
What are the 3 main classes of ß-thalassaemia?
ß-Thalassaemia trait
ß-Thalassaemia intermedia
ß-Thalassaemia major
What genetic makeup is present in ß-thalassaemia trait?
(ß ß+) or (ß ßº)
What is the clinical presentation of ß-thalassaemia trait?
This is an asymptomatic form of ß-thalassaemia
It can lead to mild or absent anaemia, with low MCV and raised HbA2
What genetic makeups are present in ß-thalassaemia intermedia?
(ß+ ß+) or (ß+ ߺ)
What is the clinical presentation of ß-thalassaemia intermedia?
This is a disease of moderate severity requiring occasional transfusion (Similar phenotype to HbH disease)
What is the genetic makeup of ß-thalassaemia major?
(ߺ ߺ)
When will ß-thalassaemias present?
Between 6 and 24 months as foetal haemoglobin falls
How will ß-thalassaemia present
- Pallor
- Failure to thrive
What are some symptoms of untreated, long-term ß-thalassaemia?
- Hepatosplenomegaly
- Skeletal changes
- Organ damage
What causes skeletal changes in ß-thalassaemia major?
Increased EPO levels due to hypoxia leads to increased bone marrow activity
This causes erythroid hyperplasia and thus expansion of the medulla of bone
What will be shown on haemoglobin analysis in ß-thalassaemia major?
High HbF
No HbA
What is the management option used in ß-thalassaemia major?
Management of ß-thalassaemia major requires regular transfusions to maintain Hb at 95-105 to suppress ineffective erythropoiesis and inhibit over absorption of iron (Hypoxia stopped, less EPO, less erythroid hyperplasia)
Bone marrow transplant may also be used if required
What is the highest cause of mortality in regular transfusion for ß-thalassaemia major?
Iron overload
