Haemaglobinopathies and sickle cell Flashcards
what is the problem in haemoglobinopathies
problems with globin chains
HbA2 has 2 alpha chains and 2 ____ chains
delta
HbA has 2 alpha chains and 2 _______ chains
beta
alpha like genes are on chromosome ___
16
beta like genes are on chromosome ___
11
adult levels of Hb reached by what age?
6-9 months
when does beta chain production kind of start
few months after birth
what are haemoglobinopathies
hereditary conditions affecting globin chain synthesis
two main groups of
- thalassaemias
- structural haemoglobin variants
thalassaemias
mutation resulted in you not producing enough of the globin chains
structural haemoglobin variants
normal production of abnormal globin chain
alpha thalassaemia
not making enough alpha globin chains
beta thalassaemia
not making enough beta globin chains
consequences of thalassaemias
inadequate Hb production —> microcytic hypochromic anaemia
If severe:
- Unbalanced accumulation of globin chains which are toxic to the cell
- Ineffective erythropoiesis
- Haemolysis
what does alpha thalassaemia result from?
results from deletion of one or both alpha genes from chromosome 16
alpha thalassaemia trait
missing one or two alpha genes
Microcytic, hypochromic red cells with mild anaemia
asymptomatic
don’t need treatment
carrier state
HbH disease
a form of alpha thalassaemia.
only one working alpha gene per cell - moderate to severe anaemia
Hb Barts hydrops fetalis
no functional α genes (–/–) incompatible with life
HbH disease signs symptoms
jaundice, splenomegaly
what is the most severe form of alpha thalassaemia
Hb Barts Hydrops Foetalis Syndrome
How can alpha thalassaemia trait be distinguished from iron deficiency?
ferritin will be normal in alpha thalassaemia trait
beta thalassaemia is usually caused by ______ mutations within the beta gene
point
alpha thalassaemia is usually to do with ________ of alpha genes
deletion
classification of beta thalassaemia
beta thalassaemia trait
beta thalassaemia intermedia
beta thalassaemia major
beta thalassaemia trait diagnosis
increased HbA2
beta thalassaemia trait
asymptomatic
do beta thalassaemia intermedia patients need transfusion?
require occasional blood transfusion
beta thalassaemia major when does it present
6-24 months (as HbF falls)
beta thalassaemia major symptoms
pallor, failure to thrive
beta thalassaemia major - extramedullary haematopoiesis complications:
- hepatosplenomegaly
- skeletal changes
- organ damage
beta thalassaemia major haemoglobin analysis
- mainly HbF
- no HbA (or possibly a little bit)
management of beta thalassaemia major
Regular transfusion programme to maintain Hb at 95-105g/l
Bone marrow transplant may be an option if carried out before complications develop
blood transfusions for management of beta thalassaemia major - what is the main cause of mortality
iron overload from transfusion
consequences of iron overload - endocrine dysfunction
Impaired growth and pubertal development
Diabetes
Osteoporosis
consequences of iron overload - cardiac disease
Cardiomyopathy
Arrhythmias
consequences of iron overload - liver disease
Cirrhosis
Hepatocellular cancer
management of iron overload
iron chelating drugs (e.g. desferrioxamine)
transfusion related complications
Viral infection - HIV, Hepatitis B and C
Alloantibodies – hard to crossmatch
Transfusion reactions
what cause sickle cell
point mutation in codon of the beta globin gene
(so altered beta chain ‘beta S’)
HbAS
sickle cell trait
asymptomatic carrier state
mainly HbA, HbS <50%
HbSS
sickle cell anaemia
HbS >80%, no HbA
sickle cell anaemia genes
two abnormal beta genes
what is sickle crisis
episodes of tissue infarction due to vascular occlusion
symptoms depend on site and severity
pain may be extremely severe
sickle crisis consequences
tissue ischaemia and pain
precipitants of sickle crisis
- hypoxia
- dehydration
- infection
- cold exposure
- stress/fatigue
sickle crisis treatment
medical emergency
- opiate analgesia
- hydration (IV fluids)
- rest
- oxygen
- antibiotics if evidence of infection
if life-threatening (if sickling is happening in lungs or brain) - red cell exchange transfusion
when would red cell exchange transfusion be used in the treatment of sickle crisis
severe crisis eg (lung) chest crisis or (brain)stroke to rapidly reduce proportion of HbS in blood
longterm management of sickle
Hyposplenism - reduce risk of infection:
- prophylactic penicillin
- vaccination; pneumococcus, meningococcus, haemophilus
Folic acid supplementation (↑ RBC turnover so ↑demand)
Hydroxycarbamide can reduce severity of disease by inducing HbF production
Regular transfusion to prevent stroke in selected cases
haemoglobinopathy diagnosis - simple first things
- FBC; Hb, red cell indices
- Blood film
- Ethnic origin
haemoglobinopathy diagnosis - high performance liquid chromatography or electrophoresis what are these tests for
to quantify haemoglobins present
Identifies abnormal haemoglobins eg HbS
Raised HbA2 diagnostic of beta thal trait
screening for haemoglobinopathies
antenatal to identify carrier parents now standard
family origin questionnaire and FBC
further testing if from high risk area or abnormal RBC indices
newborn screening programme also in place
thalassaemia trait is believed to confer some protection against _________ __________
falciparum malaria
