haemoglobinopathies Flashcards
where does synthesis of haem occur?
in normoblasts in the bone marrow
within mitochondria and cytosol
what are the normal functioning adult haemoglobins?
HbA, HbA2 and HbF
what percentage of adult haemoglobin does HbA make up? what globin chains is it made up of?
96% (major component)
2 alpha and 2 beta
what percentage of adult haemoglobin does HbA2 make up? what globin chains is it made up of?
3% (minor component)
3 alpha and 2 delta
what percentage of adult haemoglobin does HbF make up? what globin chains is it made up of?
less than 1% but it predominate haemoglobin during fetal development
2 alpha and 2 gamma
when are embryonic Hb’s seen?
only in the first trimester
what are the different kinds of haemoglobinopathies?
Hb variants
thalassaemias
what are Hb variants?
disorders that affect the structure and quantity of haemoglobin produced
what are thalassaemias?
caused by deletions in the genes that code for haemoglobin synthesis and result in reduced globin production and chain imbalance
which globin gene is affected in thalassaemia?
any chain can be affected
most deletions occur in alpha and beta thalassaemia
how can thalassaemias be detected?
by compensation through increased production of a different specific haemoglobin form and/or a decrease in other globin chains along with ‘thalassaemic’ red cell indices
when do structural variants arise in thalassaemia? and how many exist?
when one or more amino acid is substituted for a different one
over 800 different variants exist
which structural variant is most significant in thalassaemia?
sickle cell haemoglobin
what is the structural variant causes sickle cell haemoglobin?
amino acid at position 6 on the beta globin chain is substituted
glutamine to valine
are we able to detect the structural change when it is internal or external and why? what methods allow us to visualise the change?
external
it causes a change in the net charge
electrophoretic/chromatographic methods allow visualisation
when does alpha thalassaemia occur?
when some of the alpha chain gene/s are deleted
usually inherit two genes from each parent
what are the modes of inheritance for alpha thalassaemia?
alpha+ in the heterozygous form occurs when there is one gene deletion (from one parent)
alpha+ in the homozygous form occurs when there is two gene deletion (one from each parent)
alpha o in heterozygous form occurs when there are two gene deletions (2 from one parent)
HbH occurs when only one alpha gene is inherited
Hb barts is when no alpha gene is inherited. this is incompatible with life and is fatal
what populations is alpha+ heterozygous form commonly seen?
in africans, afro-caribbeans, indians, pakistanis and bangladeshi
what populations is alpha o heterozygous form commonly seen?
far east asians chinese greeks turkish some meditteranean and middle eastern europeans
what are the red cell indices involved in alpha thalassaemia?
increased RBC normal Hb decreased MCV decreased MCH normal MCHC if iron deficient then all cell indices are lowered
would the chromatogram be normal for alpha thalassaemia?
yes
normal HbA2
no treatment required
how many beta globin genes do we inherit from each parent?
one
when does beta+ thalassaemia occur?
when some of the beta globin chain is deleted
when does beta o thalassaemia occur?
when one beta globin gene is absent
would the chromatogram be normal for beta thalassaemia?
no
raised levels of HbA2 (above 3.5%) and HbF (above 1%)
clinical presentation of beta thalassaemia major
severely anaemic and ill from 6 months old
beta globin chain deleted in full
blood film of beta thalassaemia major
abnormal
low Hb
microcytic features
abnormal red blood cells
chromatogram of beta thalassaemia major
abnormal
no HbA seen
majority of Hb is HbF
what is the treatment for beta thalassaemia major?
transfusion dependant
what can HbS polymerise to form and what can it cause?
forms long crystals that can rupture cells and cause severe pain due to venous occlusion in small blood vessels
