Haemoglobinopathy Flashcards
what is the structure of adult haemoglobulin
2 alpha globin chains
2 beta globin chains
4 Haem groups (1 per chain)
what makes up Haem
porphyrin ring with iron in the middle
what are the 2 main forms of haemoglobin
HbA - adult (2 alpha, 2 beta chains)
HbA2 (2 alpha, 2 delta chains)
HbF - fetal (2 alpha, 2 gamma)
what are the percentages of the different types of Hb in the blood
97% HbA
2.5% HbA2
0-0.5% HbF
where are alpha globing genes produced
chromosome 16
where are beta globulin genes produced
chromosome 11
when do adult haemoglobin levels reach max
6-12 months
therefore beta chain problems won’t manifest until then
what are the haemoglobinopathies
hereditary conditions affecting globin chain synthesis
autosomal recessive disorders
what are the two main groups of haemoglobinopathies
Thhalassaemias
-decreased rate of normal globin chain synthesis
Structural haemoglobin variants
- normal production of abnormal global chain
- eg. sickle cell anaemia
what are the two main thalassaemia categories
alpha thalassaemia
-underproducing alpha chains
beta thalassaemia
-underproducing beta chains
what are the consequences of thalassaemias
Inadequate Hb production leading to MICROCYTIC HYPOCHROMIC ANAEMIA (small red blood cells with no Jb in them)
severe side effects of thalassaemias
unbalanced accumulation of globing chains which are toxic to the cells
haemolysis
ineffective erythropoiesis
what infectious disease is linked to thalassaemias
malarias
-haemoglobinopaties protect against malaria
what is alpha thalassaemia trait
one or two alpha chains are missing
in normal person there are 4
leads to mild microcytic hypochromic anaemia
does not need treated but need to distinguish from iron deficiency
what is HbH disease
only 1 alpha chain left
red cells are even smaller
much more serious
inherited no working genes from one parent and none from the other
what is Hb Parts hydros fetalis
no functional alpha genes
antenatal screening to avoid
gamma 4 chains and beta 4 chains form which aren’t functional
what happens in HbH disease
not enough alpha chains
therefor the beta chains form tetramers (B4) called HbH - these are non-functional
common in Asia
clinical features of Hb Parts hydros fetalis
profound anaemia cardiac failure growth retardation severe hepatosplenomegaly skeletal and cardiovascular abnormalities almost all die in utero
what is beta thalassaemia
disorder of beta chain synthesis
reduced or absent beta chain production
only HbA affected not HbF so doesn’t present until a few months into life
3 classifications of beta thalassaemia
B thalassaemia train
B thalassaemia intermedia
B thalassamia major
what is b thalassaemia major
most severe presents at 6-24 months pallor, failure to thrive extra medullar haematopoiesis causing -hepatosplenomegaly -skeletal changes -organ damage
treatment of b thalasassaemia major
regular transfusion program to maintain Hb at 95-105g/l
- suppresses ineffective erythropoiesis
- inhibit over-absorption of iron
bone marrow transplant could be an option before complications occur
risks of blood transfusions in b thalassaemia major
iron overload - can cause mortality
damages endocrine glands, heart and liver
need to give iron chelating drugs
other complications:
- infection
- alloantibodies
- transfusion reactions
- increased sepsis risk
what are sickling disorders
-making haemoglobin just abnormal Hb
altered form of haemoglobin
sickle cell anaemia = point mutation in codon 6 of the b globing gene
results in HbS production
what does HbS do to RBCs
polymerised if exposed to low oxygen levels
distorts the red cell, damaging RBC membrane
what is sickle cell trait
asymptomatic carrier - people are well
not enough HbS to cause disease (polymerise) but may sickle under severe hypoxia eg. high altitude or anaesthetic
what happens in sickle cell anaemia
two abnormal B genes
HbS>80% with no HbA
episodes of tissue infarction due to vascular occlusion - sickle crisis giving extreme pain
chronic haemolysis
hyposplenism due to repeated splenic infarcts
what is sickle cell crisis
severe pain due to vast-occlusion causing infarction of tissue
what can trigger sickle crisis
hypoxia dehydration infection cold exposure stress/fatigue
treatment of sickle crisis
opiate analgesia hydration rest oxygen antibiotics if evidence of infection red cell exchange transfusion in severe crisis eg. (Lung, or brain)
long term management of sickle cell disease
Hyposplenism - reduce risk of infection
- prophylactic penicillin
- vaccination
Folic acid supplementation
Hydroxycarbamide - induces HbF production
regular transfusion to prevent stroke
how do you diagnose a haemoglobinopathy
FBC, Hb, red cell count
blood film
ferritin - rule out iron deficiency
ethnic origin
High performance liquid chromatography to quantify haemoglobins present
what is a diagnostic trait of beta thalassamia trait
raised HbA2
