Haemoglobinopathies Flashcards
three major forms of Hb
HbA
HbA2
HbF
structure of HbA
2 alpha and 2 beta chains
structure of HbA2
2 alpha and 2 delta chains
structure of HbF
2 alpha and 2 gamma chains
which chromosome controls alpha chain production?
16 (2 genes per chromosome, 4 per cell)
which chromosome controls beta chain production?
chromosome 11 (1 gene per chromosome, 2 per cell)
define haemoglobinopathies
hereditary conditions affecting globin chain synthesis
two main groups of haemoglobinopathies
- thalassaemias
2. structural Hb variants
define thalassaemia’s
decreased rate of globin chain synthesis
define structural Hb variants
normal production of abnormal globin chains e.g. HbS
two types of thalassaemia’s
- alpha thalassaemia
2. beta thalassaemia
what is alpha thalassaemia?
deletion of alpha genes in chromosome 16 causing reduced/ absent alpha chain synthesis (all Hb forms affected)
classification of alpha thalassaemia
- alpha thalassaemia trait
- HbH disease
- Hb Barts hydrops fetalis
define alpha thalassaemia trait
one or two alpha genes are missing
asymptomatic carrier state
mild anaemia 105-110
difference between thalassaemia and iron deficiency anaemia?
ferritin is normal in thalassaemia trait
define HbH disease?
only one alpha gene left so the excess beta chains form tetramers (beta4) called HbH
blood results of HbH disease
anaemia 50-90
low MCV
low MCH
diagnosis of HbH disease
red cell inclusions of HbH seen on staining
FBC
presentation of HbH disease
jaundice
splenomegaly
anaemia
where is HbH disease common
SE Asia
management of HbH disease
transfusion
define Hb Barts hydrops fetalis
no functional alpha genes so no HbF or HbA causing tetramers of Hb Barts (gamma4) and HbH (beta4)
presentation of Hb Barts hydrops fetalis
profound anaemia cardiac failure growth retardation severe hepatosplenomegaly skeletal abnormalities most die in-utero
diagnosis of Hb Barts hydrops fetalis
antenatal screening
risk increased if both parents from SE Asia
common cause of beta thalassaemia
point mutations
which Hb is affected in beta thalassaemia?
only HbA
classification of beta thalassaemia
- beta thalassaemia trait
- beta thalassaemia intermedia
- beta thalassaemia major
presentation of beta thalassaemia trait
asymptomatic
no/mild anaemia
low MCV/MCH
what is diagnostic of beta thalassaemia trait?
raised HbA2
presentation of beta thalassaemia major
6-24 months pallor failure to thrive hepatosplenomegaly skeletal changes organ damage
how are beta thalassaemia intermedia and beta trait different?
trait= one reduced/ absent intermedia= both reduced or one reduced, one absent
what causes hepatosplenomegaly, skeletal changes and organ damage in beta thalassaemia major
extramedullary haematopoiesis
complication of extramedullary haematopoiesis
spinal cord compression
diagnosis of beta thalassaemia major
mainly HbF and no HbA
hair on end skull XR
management of beta thalassaemia major
regular transfusions
bone marrow transplant
why are regular transfusions carried out in beta thalassaemia major?
maintain Hb 95-105g/l
suppress ineffective erythropoiesis
inhibit overabsorption of iron
endocrine complications of iron overload
impaired growth
hypogonadism
diabetes
OP
cardiac disease complications of iron overload
cardiomyopathy
arrhythmias
liver disease complications of iron overload
cirrhosis
hepatocellular carcinoma
why can iron overload cause sepsis?
bacteria likes iron
management of iron overload in haemoglobinopathies
iron chelating drugs e.g. desferrioxamine
not venesection as already anaemic
cause of sickling disorders
point mutation in codon 6 of the beta globin chain that substitutes glutamine to valine producing Bs.
altered structure resulting in HbS
what does HbS do when exposed to low oxygen levels?
polymerises
classification of sickling disorders
- sickle cell trait (HbAS)
- sickle cell anaemia
- sickle cell disease
what is sickle cell trait?
one normal and one abnormal beta gene
presentation of sickle cell trait
asymptomatic as HbS level too low to polymerise
diagnosis of sickle cell trait
blood film mainly HbA and HbS <50%
what is sickle cell anaemia?
two abnormal beta cells
diagnosis of sickle cell anaemia
HbS >80% and no HbA
what is sickle crisis?
episode of tissue infarction due to vascular occlusion
why is there chronic haemolysis in sickle cell anaemia?
shortened RBC lifespan
why is there hyposplenism in sickle cell anaemia?
splenic infarcts
what is sickle cell disease?
compound heterozygosity for HbS and another beta chain mutation e.g. HbS/ beta thalassaemia or HbSC disease (two types of B variants)
precipitants of sickle crisis
hypoxis dehydration infection cold exposure stress fatigue
management of sickle crisis
opiate analgesia for severe pain
hydration, rest, oxygen, antibiotics if infection
red cell exchange in severe crisis (venesect > transufse > venesect > transfuse)
diagnosis of sickling disorders
FBC, Hb, red cell indices, blood film ethnic origin HPLC or electrophoresis for abnormal HbS raised HbA2 in beta trait antenatal screening
management of hyposplenism
prophylactic antibiotics
vaccines
management of sickling disorders
hyposplenism management
folic acid supplements (increased RBC turnover increases demand)
hydroxycarbamide induces HbF production
regular transfusions
