Haemoglobinopathies Flashcards
what chromosome are alpha genes found on?
16
(2 per chromosome)
what chromsome are beta genes found on?
11
(1 per chromosome)
at what age are adult levels of Hb achieved?
6-12 months
how can haemoglobinopathies interfere with HbA1c?
they can give falsely low HbA1c as shorten the life span of RBC
conditions affecting globin chain synthesis are usually what pattern of inheritance?
autosomal recessive
what is thalassaemia?
decreased rate of globin chain synthesis
why are unbound globin chains dangerous?
they are toxic and result in haemolysis
inadequate Hb production in thalassaemia will lead to what kind of anaemia?
microcytic hypochromic anaemia
in alpha thaassaemia how many genes are lost in
1) alpha 0
2) alpha +
1) 2/4 genes lost
2) 1/4 genes lost
what is the severe form of alpha thalassaemia called?
HbH disease- 1 gene per cell
how is HbH formed in HbH disease?
excess B chains form tetramers called HbH which can’t carry oxygen
what symtpoms are seen in HbH disease?
jaundice due to haemolysis
inefective erythropoiesis
splenomegaly
what is the severst form of alpha thalassaemia?
Hb Barts hydrops fetalis syndrome
how many alpha genes are inherited in Hb Barts?
no alpha genes inherited from either parent- cannot make HbA
what kind of Hb is made in Hb Barts?
HbF- four gamma chains, extremely high affintiy fro oxygen to hardly any delivery to tissues
what kind of mutation usually causes disorder of beta chain synthesis in beta thalassaemia?
point mutation
does beta thalassaemia affect HbA and HbF?
no- only afects adult haemoglobin not foetal
how is beta thalassaemia intermedia treated?
occasional transfusion
(moderate severity)
when does beta thalassaemia major present?
6-24 months (as HbF falls)
what is the management of beta thalassaemia major?
regular transfusion to maintain Hb
what is the main concern with regular transfusions in beta thalassaemia major?
iron overload
if you suspect a thalassaemia what else should you check first to rule out anaemia?
ferritin
what are chelating drugs?
bind to iron formign complexes that can then be excreted in urien or stool
what is an example of a chelating drug used in iron overload?
desferrioxamine
in sickling disorders what gene suffers a point mutation?
B globin gene
what is glutamine substituted to in sickling disorders?
valine
what is the genotype of someone with sickle cell trait?
one abnormal, one normal gene
is sickle cell trait symtpomatic?
No- asymtpomatic in carrier state
what inheritance is sickle cell anaemia?
autosomal recessive
what would appear on teh blood film of somone with sickle cell anaemia?
sickle red cells as all HbS and no HbA
what can occur in sickle cell anaemia?
sickle crisis
chronic hameolysis
hyposplenism
what is sickle crisis?
tissue infarction due to distorted sickle cells occluding vessles- causes ischaemia and pain
why do people with sickle cell anaemia suffer hyposplenism?
due to repeated splenic infarcts
what is the treatment of Sickle Crisis?
strong analgesia
IV/fluids hydration
oxygen
treat any infection
red cell exchange in severe crisis
what are the long term effects of sickle cell anaemia?
impaired growth
risk of end organ damge with recurrent crisis i.e. pulmonary hypertension/stroke
what are the management options for sickle cell anaemia?
folic acid supplementation
hydroxycarbamide
regular transfusion in select cases
why is hydroxycarbamide helpful in managing sickle cell anaemia?
tricks body into producing HbF instead of HbS
how is liquid chromatography helpful in haematology?
height of peak corresponds to how much of that Hb is present
