Haemoglobinopathy Flashcards
HbA2 is made up of what chains?
2 alpha 2 delta
main form of Hb
HbA (2 alpha 2 beta)
alpha like genes are found on what chromosome?
16
beta like genes are found on what chromosome?
11
when are adult levels of Hb reached after birth?
6-12 months
how does fetal Hb become adult Hb?
gamma chains switched off, beta chains switched on and replace it
what are haemoglobinopathies?
hereditary conditions affecting the globin chain
what happens in thalassaemia?
make a globin chain but not ENOUGH of it because of decreased rate of globin chain synthesis
what happens in structural Hb variants?
make a structurally abnormal globin chain
name the 2 main types of h-opathy
thalassaemia
structural Hb variants
2 types of thalassaemia
alpha and beta (depending on which chains are affected)
what anaemia is caused from thalassaemia and why?
microcytic hypochromic anaemia because of inadequate Hb production from lack of or ineffective globin
why do you get haemolysis and ineffective erythropoesis in thalassaemia?
unbalanced accumulation of globin chains is toxic
thalassaemia is mono/polygenic
mono
normally have _ alpha genes per cell, _ from each parent
4
2
normally have _ beta genes per cell, _
from each parent
2
1
what types of Hb are affected in alpha thalassaemia?
all of them as they all contain alpha chains
what happens when you lose all your alpha genes?
hydrops fetalis
what is HbH disease?
only 1 functional alpha chain out of 4
how many genes are lost to give you alpha thalassaemia trait?
one or two
symptoms of alpha thalassaemia trait
asymptomatic
describe a film of alpha thal trait
microcytic, hypochromic red cells
mild anaemia
how can you differentiate alpha thal trait from ID anaemia?
ferritin is normal in ATT
describe a blood film of HbH disease
anaemia
VERY low MCV
MCH
what is HbH
tetramers formed by excess B chains in the presence of alpha thalassaemia
clinical presentation of HbH
SE asian patient
moderate-severe anaemia
splenomegaly
jaundice from haemolysis/ineffective erythopoesis
why do patients with thalassaemias get splenomegaly sometimes?
undergo extramedullary haematopoesis as bone marrow cant make RBCs
clinical features of hydrops fetalis
severe anaemia cardiac failure growth retardation severe hepatosplenomegaly skeletal problems death in utero
blood film of hydrops fetalis?
nucleated RBCs in peripheral blood
genetic cause of beta thal?
point mutation
what Hb type is affected in beta thal?
HbA
name the 3 types of beta thal
b thal trait
b thal intermedia
b thal major
symptoms of b thal trait
asymptomatic
no/mild anaemia
low MCV/MCH
what Hb type is raised in b thal trait
raised HbA2
which type(s) of b thal is/are transfusion dependent
b thal major
when does b thal major present? why?
6-24 months
HbF falls and HbB should take over
clinical presentation of b thal major
pallor failure to thrive hepatosplenomegaly skeletal changes organ damage (from extramedullary haematopoesis)
what Hb types are most prominent in b thal major?
HbF mainly
minimal HbA
complication of extramedullary haematopoesis
cord compression
Tx b thal major
transfusion- Hb 95-105g/l
BM transplant
main complication of transfusion in b thal major
iron overload
consequences of iron overload in thalassaemia?
endocrine- impaired growth/diabetes/osteo
cardiac disease - arrhythmias/myopathy
liver - cirrhosis/hepatocellular cancer
Tx iron overload
iron chelating drug eg desferrioxamine
keep iron to 250mg per unit of red cells in transfusions
what do iron chelating drugs do?
bind to iron to create a complex that allows it to be excreted
genetic cause of sickle cell? what substance is affected?
point mutation in the B globin gene
produces substance called “beta S”
what is the Hb structure in sickle cell?
HbS (A2 BS2)
describe the B genes in sickle trait
1 normal B gene
1 abnormal Bs gene
sickle trait is asymptomatic T or F
T
what Hb type is mainly in sickle trait?
HbA
do get HbS
B genes present in sickle cell anaemia?
2 Bs genes
inheritance of SCA
AR
what types of Hb are present in SCA
HbS in most
NO HbA!!
what is sickle crisis?
episodes of tissue infarction due to vascular occlusion by wedged sickle cells
symptoms of sickle crisis
depend on site and severity
pain
locations of sickle crisis?
digits, BM, lung, spleen, CNS
why is there haemolysis in SCA?
RBCs have much shorter life span as they have a sickle shape
precipitants of sickle crisis
hypoxia dehydration infection cold stress/fatigue
Tx sickle crisis
opiate analgesia hydration rest O2 antibiotics if infection venesect-transfuse if severe
why do SCA patients get hyposplenism
common site of infarction in sickle crisis
long term effects of SCA
impaired growth
end organ damage eg pulm HT, renal disease, stroke
long term Tx of SCA
prophylactic ABs for hyposplenism
folic acid supplements to inc RBC turnover
hydroxycarbamide
regular transfusion
Ix haemoglobinopathy
FBC
Hb
red cell indices
liquid chromatography orgel electrophoresis to check what Hbs are present
raised HbA2 is diagnostic of….
beta thal trait
