Haemoglobinopathies Flashcards
describe the structure of Hb
a tetramer made of two alpha globin chains and two beta globin chains, with one haem group attached to each globin
describe the structure of haem
a porphyrin ring with an iron at the centre
what causes the development of haemoglobinopathies?
problems with the globin chains
what is HbA?
adult haemoglobin
two alpha and two beta chains
what is HbA2?
2 alpha chains and 2 delta chains
a functional but rare form of Hb
what is HbF?
fetal haemoglobin
two alpha and two gamma chains
where are the genes for alpha globin chains found and how many are there per cell?
chromosome 16
two per chromosome = four per cell
where are the genes for beta globin chains found and how many are there per cell?
chromosome 11
one per chromosome = two per cell
when are levels of adult hemoglobin reached and what implication does this have for globin problems?
6-12 months of age
means problems with the beta chain wont manifest til this time, as beta globin is only found in HbA
what are haemoglobinopathies?
hereditary conditions affecting globin chain synthesis
what is the inheritance pattern seen in haemoglobinopathies?
autosomal recessive
what are the two main groups of haemoglobinopathies?
thalassaemia
structure Hb variants
what infection has been associated with increased rates of haemoglobinopathies in certain areas?
malaria
what are the two types of thalassaemia?
alpha thalassaemia
beta thalassaemia
what type of anaemia is seen in thalassaemia and why?
inadequate Hb production causes a microcytic hypochromic anaemia
what causes alpha thalassaemia?
mutations affecting alpha globin chain synthesis
what genotype is seen in individuals unaffected by alpha thalassaemia?
four normal alpha genes = (aa/aa)
what types of haemoglobin can be affected by alpha thalassaemia?
all as they all contain alpha globin (HbA, HbA2 and HbF)
what are the three types of alpha thalassaemia?
alpha thalassaemia trait
HbH disease
Hb Bart’s hydrops fetalis
what is the genotype of someone with alpha thalassaemia trait?
one or two alpha genes missing i.e. (-a/aa) or (–/aa)
how does alpha thalassaemia trait present?
asymptomatic carrier state
microcytic hypochromic red cells with normal ferritin
what genotype is seen in people with HbH disease?
only one alpha gene left (–/-a)
how does HbH disease present?
moderate to severe anaemia with very low MCV and MCH
what is a+ thalassaemia?
one alpha gene deleted from a chromosome (-a/aa)
what is a0 thalassamia?
both alpha genes deleted from a chromosome (–/aa)
why is HbH disease called that?
excess beta globin chains form tetramers
in which area is there a higher prevalence of HbH disease?
south east asia
what is the genotype seen in Hb Bart’s?
no functional alpha genes (–/–)
how does Hb Bart’s usually present?
intrauterine death as not compatible with life
what causes beta thalassaemia?
point mutations in the beta globin chain resulting in disordered beta chain synthesis
what type of Hb is affected by beta thalassaemia?
only HbA as this is the only type that contains beta chains
what does B+ mean?
reduced beta chain production
what does B0 mean?
absent beta chain production
what are the three types of beta thalassaemia?
beta thalassaemia trait
beta thalassaemia intermedia
beta thalassaemia major
what genotypes can be seen in beta thalassaemia trait?
B+/B or B0/B
how does beta thalassaemia trait present?
asymptomatic
may have a mild anaemia
low MCV/MCH
what is diagnostic of beta thalassaemia trait?
raised HbA2 levels
what genotypes can be seen in beta thalassaemia intermedia?
B+/B+ or B0/B+
what do patients with beta thalassaemia intermedia need?
occasional transfusions
what genotype is seen in beta thalassaemia major?
B0/B0
what do patients with beta thalassaemia major need?
lifelong transfusions
when does beta thalassaemia major present and why?
6-24 months old as HbF falls
how does beta thalassaemia major present?
pallor
failure to thrive
what is the Hb target in beta thalassaemia major?
95-105
what is a possible management option for beta thalassaemia major if done early?
bone marrow transplant
what three systems can be impacted by iron overload?
endocrine
cardiac
liver
what effects can iron overload have on the endocrine system?
impaired growth + development
diabetes
osteoporosis
what effects can iron overload have on the heart?
cardiomyopathy
arrythmias
what effects can iron overload have on liver disease?
cirrhosis
HCC
how should iron overload be managed in an anaemic patient?
iron chelating drugs
name an iron chelating drug
desferrioxamine
what causes sickling disorders?
point mutation in codon 6 of the beta globin chain, producing Bs
alters the structure of Hb
what type of Hb is seen in sickling disorders?
HbS
what are the three types of sickling disorders?
sickle cell trait
sickle cell anaemia
sickle cell disease
what haemoglobin is seen in sickle cell trait?
HbAS
majority is HbA
what genotype is seen in sickle cell trait?
B/Bs (one normal one abnormal)
how does sickle cell trait present?
asymptomatic carrier state
may sickle in severe hypoxia
describe the appearance of the blood film in sickle cell trait
normal
what haemoglobin is seen in sickle cell anaemia?
HbSS
what genotype is seen in sickle cell anaemia?
Bs/Bs
two abnormal B genes
how does sickle cell anaemia present?
episodes of sickle crisis causing severe pain
what causes sickle crisis?
altered shape of RBCs resulting in vascular occlusion and tissue infarction
what happens to the RBC lifespan in sickle cell anaemia?
reduced due to chronic haemolysis
where are sickled RBCs removed in sickle cell anaemia and what effect can this have?
liver and spleen
hyposplenism
name some possible precipitants of sickle crisis
hypoxia
dehydration
infection
stress
how is sickle crisis managed?
opiate analgesia
hydration
rest
oxygen
what needs to be given to patients with sickle cell anaemia due to hyposplenism?
prophylactic penicillin
regular immunisations
what is sickle cell disease?
when patients have compound heterozygosity for HbS and another B chain mutation
what investigations can be used to diagnose haemoglobinopathies?
HPLC
electrophoresis (less common)
