haemoglobinopathies Flashcards
How many haem groups on each globin chain?
1
Hb is a tetramer made up of how many aloha and beta chains?
2 alpha 2 beta
what is the major form of haemoglobin present in adults?
HbA
what types of chain are in HbA2?
a2d2
which chromosome are alpha genes on?
16
how may alpha genes are there per cell?
2 per chromosome (4 per cell)
beta like genes are on chromosome?
11 (believe)
what age are is adult haemoglobin present?
6-12 months of age
what are haemoglobinopathies?
hereditary conditions affecting globin chain synthesis
What is the difference between thalassaemias and structural haemoglobin variants?
thalassaemias are decreased rate of globin chain synthesis. structural haemoglobin variants are normal production of structurally abnormal globin chain e.g.. HbS
two types of thalassaemia?
alpha and beta
what type of anaemia do you get in thalassaemia?
microcytic hypochromic
why would you get ineffective erythropoiesis and haemolysis?
you get unbalanced accumulation of globin chains which is toxic.
(αα/αα). If someone has four normal a genes, will they be normal?
unaffected
what mutations can you get on chromosome 16 to cause alpha thalassaemia?
deletion of one or both alpha genes from chromosome 16
why is losing ability to produce alpha chains so important?
they are present in all forms of Hb
what is alpha thalassaemia trait?
having one or two genes missing from the 4
how many alpha genes do you have in HbH disease?
only 1 left
how many functional alpha genes do you have left in Hb barts hydrous fettles?
none (no functional alpha genes) (–/–)
In alpha thalasaemia trait, patient is asymptomatic with microcytic hypo chromic red cells. is any treatment needed?
no
In which disease do beta chains form tetramers which can’t carry oxygen?
HbH disease
red cell inclusions of what can be seen with special stains?
HbH
what are MCV and MCH levels like in HbH?
very low
why do you get jaundice in HbH?
haemolysis and ineffective erythropoiesis
what do severe cases of HbH need?
splenectomy and transfusion
what is the severest for of alpha thalassaemia?
Hb barts hydrops fetalis (no alpha gene inherited from either parent (–/–)
what happens to HbA in parts hydrous fetalis?
it can’t be made
clinical features of hb barts hydrops fetalis?
severe anaemia, cardiac failure, growth retardation, severe hepatosplenomegaly, skeletal and cardiovascular abnormalities
what is the outcome of hb barts hypos fetalis?
almost all die in utero
Beta thalassaemias are usually casued by?
point mutations
what is the only type of haemoglobin affected in beta thalassaemia?
HbA (a2b2)
why would you get a raised HbA2 in beta thalassaemia trait?
can’t produce beta chains so can’t produce HbA
3 classifications of beta thalassaemia?
trait, intermedia and major
when do patients with b thalassaemia major present?
6-24 months old (as HbF falls off)
on hb analysis in b thalassaemia major, what would you see?
mainly HbF, minimal HbA
in b thal major, you get extra medullary haematopoesis causing?
hepatosplenomegaly, skeletal changes and organ damage
management of b thalassaemia major?
regular transfusion programme to maintain Hb at 95-105
what is the main cuase of mortality in b thal major?
iron overload from transfusion
what are the consequences of iron overload?
endocrine dysfunction, cardiac disease, liver disease
why do you get iron overload in transfusion?
250mg of iron per unit of red cells. chronic anaemia drives increased iron absorption.
what are iron chelating drugs. example of one?
they bind to iron and form complexes which are excreted in urine or stool
why do you get increased risk of sepsis with iron?
bacteria like iron
why do you get sickling disorders?
point mutation in b globin gene that substitutes glutamine to valine producing Bs
what haemoglobin do you get in sickle cells ?
A2Bs2
what happens to HbS if its exposed to low oxygen concentrations for long periods?
polymerises. This distorts the red cell, damaging the rbc membrane
sickle cell trait is an asymptomatic carrier state. when would they sickle?
in severe hypoxia e.g. high altitude or under anaesthesia
The blood film is normal. what is the percentage of HbS?
less than 50%
in sickle cell anaemia (HbSS) you have 2 abnormal beta genes. what inheritance is this?
autosomal recessive
mode of inheritance of von willebrands disease?
autosomal dominant
levels of HbS?
> 80%
what is sickle cell crisis?
Episodes of tissue infarction due to vascular occlusion
levels of HbA in sickle cell?
0
what happens to sickled red blood cells?
they are sequestrated in liver and spleen
why do you get hyposplenism ?
repeated splenic infarcts
why would you get tissue infarction and extreme pain?
sickle cell vaso occlusion
precipitants of sickle cell crisis?
hypoxia dehydration infection cold exposure stress/fatigue
treatment of painful crisis
Opiate analgesia Hydration Rest Oxygen Antibiotics if evidence of infection Red cell exchange transfusion in severe crises eg chest crisis or neurological symptoms
why do you need folic acid supplementation in sickle cell?
increased cell turnover so increased demand
what does hyposplenism do to risk of infection?
increases risk of infection
what tests can you do to quantify haemoglobin present?
High performance liquid chromatography (HPLC) or gel electrophoresis
Raised HbA2 diagnostic of?
b thalassaemia trait
HPLC normal in?
alpha thal trait so DNA testing needed to confirm
Microcytic hypochromic RBCs not always due to iron deficiency
y
what is the pathophysiology of G6PD deficiency?
Reduced G6PD reduced glutathione increased red cell susceptibility to oxidative stress
what can cause G6PD?
drugs such as ciprofloxacin, anti malarial and sulph group drugs such as SUs
what is the sign seen on blood film in G6PD deficiency?
heinz bodies
