Haemoglobinopathies Flashcards
What is the most common monogenic disorder worldwide
haemoglobinopathies
what is the structure of Hb
tetramer - 4 globin chains
2 alpha 2 beta
1 haem attached to each globin chain
what is the function of globin in Hb
to keep haem soluble and protect it from oxidation
what are the main types of Hb and what are they made up of
HbA = 2a and 2B HbA2 = 2a and 2delta HbF = 2a and 2gamma
on which chromosome are alpha like genes found
16
how many alpha genes are found on each chromosome
2 per chromsome
4 per cell
on which chromosome are beta like genes found
11
how many beta genes are found on each chromosome
1 per chromosome
2 per cell
expression of globin gene changes throughout embryonic life and childhood, true or false
true
which type of globin is found in all types of Hb
alpha chain globins
levels of which globins increase during the foetal period
alpha and gamma
what happens to globin levels at birth
gamma levels decrease
beta levels increase
when are adult levels of Hb reached after birth
6-12 months old
define haemoglobinopathy
hereditary condition with impaired globin synthesis
how are haemoglobinopathies inherited usually
AR
how are haemoglobinopathies classified
reduced globin synthesis - thalassaemia
abnormal globin struture - sickled
define thalassaemia
reduced globin chain synthesis resulting in decreased Hb synthesis
what is the abnormality in alpha thalassaemia
defect in alpha chain - not enough alpha globulin
what is the abnormality in beta thalassaemia
defect in beta chain - not enough beta globulin
what are the consequences of thalassaemia
microcytic hypochromic anaemia
unbalanced accumulation of globin chains
haemolysis
ineffective erythropoeisis
what is ineffective erythropoeisis
precurosor cells die in bone marrow because they are that bad
what types of Hb does aloha thalassaemia affect
all kinds because all Hb types contain alpha chains
what is the genotype of an unaffected person in alpha thalassaemia
presence of all 4 normal alpha genes
aa/aa
what can alpha thalassaemia do to levels of alpha globin
reduced or absent levels
how is alpha thalassaemia classified
according to number of affected alpha genes
describe alpha thalassaemia trait genotype
loss of 1 or 2 alpha genes
describe HbH disease genotype
only 1 alpha gene is left out of 4
–/-a
describe Hb Barts Hydrops Fetalis genotype
no functional alpha genes at all
–/–
describe the features of alpha thalassaemia trait
asymptomatic carrier with no treatment required
microcytic hypochromic cells with mild anaemia
are ferritin levels high or low in alpha thalassaemia trait
normal - excludes iron deficiency
describe the feature of HbH disease
more severe form of alpha thalassaemia
anaemia with low MCV and MCH
what happens to excess beta chains in HbH disease
they form tetramers B4 called HbH
clinical features of HbH disease
jaundice
splenomegaly
may need transfusion
describe features of Hb Barts Hydrops Fetalis
most severe form of alpha thalassaemia
no alpha chains results in Hb Barts (gamma4) and HbH (B4)
clinical features of Hb Barts
profound anaemia incompatible with life cardiac failure growth retardation severe hepatosplenomegaly
what is the cause of beta thalassaemia
point mutation resulting in reduced or absent B globulin
which type of Hb is affected in beta thalassaemia
HbA as it is the only one containing beta chains
how is beta thalassaemia classified
according to clinical severity
what are the subtypes of beta thalassaemia
beta thalassaemia trait
beta thalassaemia intermidia
beta thalassaemi major
what is the genotype of beta thalassaemia trait
B+/B or Bo/B
what are the features of beta thalassaemia trait
asymptomatic
no/mild anaemia
low MCV/MCH
raised HbA2
what is diagnostic of beta thalassaemia trait
raised HbA2 levels
what is the genotype of beta thalassaemia intermedia
B+/B+ or Bo/B+
what are the features of beta thalassaemia intermedia
moderate severity
requires occasional transfusion
what is the genotype of beta thalassaemia major
Bo/Bo
what are the feature of beta thalassaemia major
no beta chain synthesis
cannot make HbA
severe lifelong transfusion dependency
when does beta thalassaemia major present
6-24 months old
as HbF goes down and body tries to make HbA
consequences of beta thalassaemia major
extramedullary haemoatopoeisis hepatosplenomegaly skeletal defects organ damage spinal cord compression
what is extramedullary haemoatopoeisis
RBC production outwith the bone marrow ie in liver and spleen leading to hepatosplenomegaly
management of beta thalassaemia major
regular tranfusion programme
maintain Hb at 95-105g/L
bone marrow transplant curative
what is a complication of lifelong blood transfusions
iron overload
what are complications of iron overload
endocrine: DM and pancreas, osteoporosis, impairs growth
cardiac: cardiomyopathy, arrhythmias
liver: cirrhosis, HCC
sepsis: bacteria love iron
management of iron overload in beta thalassaemia major needing lifelong transfusion
iron chelating drugs eg desferrioxamine
what is the cause of sickling disorders
point mutation in codon 6 of beta globin chain in chromosome 11 substitutes glutamine for valine which produces Bs
what is the structure of HbS
2 alpha and 2 Bs
why is HbS bad
HbS polymerises if exposed to low oxygen levels for a long time which distorts the shape of the RBC and membrane
what is the genotype of sickle cell trait
1 normal and 1 abnormal beta chain
B/Bs
features of sickle cell trait
asymptomatic carrier state
few clinical features as HbS levels are too low to polymerise
can cells sickle in sickle cell trait
may sickle in severe hypoxia eg high altitude or anaesthesia
what is seen on the blood film of sickle cell trait
HbA
HbS <50%
what is the genotype of sickle cell anaemia HbSS
Bs/Bs
what proportion of HbS is present in HbSS
> 80%
why are sickle cells dangerous
disrupt microvasculature and cause vaso-occlusion resulting in tissue ischaemia and pain
why do you get hyposplenism in HbSS
due to multiple splenic infarcts
what is a sickle crisis
episodes of tissue infarction dur to vascular occlusion
severe pain depending on site affected
list precipitants of a sickle crisis
hypoxia dehydration stress cold infection or none
what is the acute management of a sickle crisis
opiate analgesia rehydration oxygen rest antibiotics if there are signs of infection
red cell exchange transfusion
what is involved in red cell exchange transfusion
venesection –> transfusion –> venesection –> transfusion …
what is the long term management of HbSS
hyposplenism: prophylactic penicillin and vaccinations
folic acid
hydroxycarbamide
regular transfusion in some cases to prevent stroke
what is the role of hydroxycarbamide
induces HbF production to reduce disease severity
what investigations are done to diagnose haemoglobinopathies
FBC iron studies blood film - microcytic hypochromic cells ethnicity Hb measures: HPLC and electrophoresis
what is HPLC
high performance liquid chromatography
