Haemaglobinopathy Flashcards
what is tetramer made up of
2 alpha global like chains and 2 beta global like chains
how many haem groups attach to a global chain
1:1
what are the major forms of hb
HbA - 2 alpha 2 beta
HbA2 - 2 alpha, 2 delta
HbF - 2 alpha, 2 gamma
what are the commonest forms of hb
HbA - 97%
HbA2 2.5%
HbF 0.5%
genetic control of alpha like genes
on chromosome 16
2 alpha genes per chromosome and 4 per cell
genetic control of beta like genes
chromosome 11
one beta gene per chromosome - 2/cell
when does expression of global genes change
through embryonic life and childhood
how are genes arranged
in order of expression
which genes in embryo
chromosome 16 - gower1, portland, gower 2
foetal hb
hbf
adults hb
hba2
hba
when are adult levels reached
by 6-12 months of age
what are haemoglobinopathies
heredity conditions affecting global chain synthesis
autosomal recessive
what are the two main groups pf hbp
thalassaemia - decreased rate of global chain synthesis
structural hb varients - normla production of structural abnormal global chain leading to variant hb such as HbS
types of thalassaemias
alpha thalassaemia - alpha chains affected
beta - beta chains affected
what does thalassaemia lead to
inadequate hb procuditon leading to microcytic hypochromin anaemia
unbalanced accumulation of global chains leading to ineffective erythropoiesis and haemolysis
why are thalassaemias important
commonest monogenic disorders
major cause of morbidity
becoming more common in the uk
why is thalassaemia more prevalent in certain areas
selective pressure in malaria endemic areas has allowed these mutations to flourish
what happens during alpha thalassaemia
why
which hb is affected
reduced of absence of synthesis of alpha chain
deletion of one or both alpha genes from chromosome 16
alpha chains present in all adult forms of hb are effected - hba, hba2, hbf
classification of alpha thalaaaemia
unaffected have 4 normal alpha genes
alpha thal trait - one of two genes missing
HbH disease - only one alpha left
Hb Barts hydrops fetales - no functional alpha genes
alpha trait symp rx signs why is it important
–/aa or -a/-a
asymp
no rx needed
microcytic hypo chromic red cells with mild anaemia
important as can be mistaken for iron defic but ferratin normal and red blood cell count raised
HbH dx what is it chain production outcome what can be seen on a stain
severe form of alpha thalaeeaemia
only one alpha gene per cell so –/-a
alpha chain production is <30% than normal
anaemia with low MCV and MCH
excess beta chains form tetramers beta4 called HbH which can’t carry oxygen
red cell inclusions (HbH bodies) can be seen w special stains
clinical features of HbH dx
mild anaemia -> transfusion dependant
splenomegaly due to extramedullary haemtopoiesis
jaundice due to haemolytic and inffecetive erythropoiesis
growth retardation
gallstones
iron overload
severe cases - splenectomy+/- transfusion
where is HbH common
middle east
SE asia
mediterranaean
Hb Barts hydrops fetales synd
severest form of alpha thallassaemia
no a genes inherited (–/–)
minimal or no alpha chain production -? HbA can’t be made
clinical features of Barts
severe anaemia cardiac failure, oedema growth retardation severe hepatosplenomegaly skeletal and cardiovascular abnormalities most die in utero
b thalassaemia is what
caused by what
how many mutations have been identified so far
reduced or absent beta chain production
only beta chains so only HbA affected
usually caused by point mutations
over 200 so far
classification of BT
beta thalassaemia trait - asymp, no or mild anaemia, low MCV and MCH
betal thallasaemia intermdiate - mod serverity requiring occasional transfusion
beta thalassaemia major- severe life long transfusion dependency
lab features of beta thal major
severe anaemia
reticulocytosis, very low MCV/MCH
film: microcytosis, hypochromia, anisopoikilocytosis and target cells
HPLC: mainly HbF present small amounts of HbA
clinical features of beta thal major
presents aged 6-24 months
failure to thrive
pallor
extra medullary haemopoiesis causing: hepatosplenomegaly, skeletal damage, organ damage, cord compression
management of beta thal major
regular transfusion programme to maintain Hb at 95-105g/l to suppress ineffective erythropoiesis and inhibit over absorption of iron
allows for relatively normal growth and development
iron overload from transfusion then becomes the main cause of mortality
bone marrow transplant can be an option if carried out before complications develop
clinical features of beta thal major
presents aged 6-24 months
failure to thrive
pallor
extra medullary haemopoiesis causing: hepatosplenomegaly, skeletal damage, organ damage, cord compression
management of beta thal major
regular transfusion programme to maintain Hb at 95-105g/l to suppress ineffective erythropoiesis and inhibit over absorption of iron
allows for relatively normal growth and development
iron overload from transfusion then becomes the main cause of mortality
bone marrow transplant can be an option if carried out before complications develop
consequences of iron overload
endocrine dysfunction - impaired growth and pubertal development, DM, osteoporosis
cardiac - cardiomyopathy, arrhythmias
liver dx - cirrhosis, herpatocellular cancer
management of iron overload
250mg of iron per unit of red cells
chronic anaemia -> increased absorption of iron from gut
venesection not feasible as already anaemic
chelators bind to iron, complexes formed excreted in urine or stool
what is the natural mechanism for iron excretion
there is none
other transfusion related complications
viral infection - HIV, hep B and C
alloantibodies - hard to crossmatch suitable blood
transfusion reactions
increased risk of bacterial sepsis as bacteria like iron
diagnosis of thalassaemia
thal trait usually suspected form red cell indices and ethnic origin - exclude iron defic first
blood film: hypochromia, target cells, anisopoikilocytosis
HPLC: Hba, Hba2, Hbf, abnormal hb, raised Hba2 diagnostic for beta thal - will be normal in alpha thal so DNA testing needed to confirm
screening for haemoglobinopathies
antenatal screening to identify carriers
newborn screening programme for couple at risk
