Haemoglobinopathy Flashcards
structure of haemoglobin
tetramer made of 2 alpha and 2 beta chains
how many haem groups are attached to each globin chain
one
use of globin chains on heme
keep it soluble and protect it from oxidation
in adults which form of haemoglobin is major present form
HbA
major forms of haemoglobin
HbA 2 alpha chains and 2 beta chains α2β2
HbA2 2 alpha and 2 delta chains α2δ2
HbF 2 alpha and 2 gamma chains
what are haemoglobinopathies
term for any hereditary conditins affecting global chain synthesis
autosomal recessive
two groups of haemoglobinopathies
Thalassaemias; decreased rate of globin chain synthesis
Structural haemoglobin variants; mutations in globin genes leading to altered structures of haemoglobin molecule
consequences of thalassemias
Inadequate Hb production → microcytic hypochromic anaemia
If severe:
Unbalanced accumulation of globin chains which are toxic to the cell
Ineffective erythropoiesis
Haemolysis
alpha thalassaemia
mutations affecting alpha globin chain synthesis
results from deletion
normal people have four alpha genes
alpha thalassaemia trait
one or two alpha genes missing
asymptomatic carrier state, microcytic hypochromic red cells but ferritin normal
HbH disease
only one alpha gene left
moderate to severe anemia
very low MCV and MCH
jaundice, splenomegaly
common in se asia
hb barts hydrops fetalis
no functional alpha genes
incompatible with life
Profound anaemia
Cardiac failure
Growth retardation
Severe hepatosplenomegaly
Skeletal and cardiovascular abnormalities
Almost all die in utero
beta thalassaemia and common cause
disorder of beta chain synthesis and caused by point mutations
b thalassaemia major
Presents aged 6-24 months (as HbF falls)
Pallor, failure to thrive
Extramedullary haematopoiesis causing;
Hepatosplenomegaly
Skeletal changes
Organ damage
lifelong transfusion dependancy
consequences of iron overload
Endocrine dysfunction
Impaired growth and pubertal development
Diabetes
Osteoporosis
Cardiac disease
Cardiomyopathy
Arrhythmias
Liver disease
Cirrhosis
Hepatocellular cancer
cause of sickle cell
point mutation i codon 6 of the b globin gene that substitute glutamine to valine producing bs
mutation alters the structure of the resulting hb > hbs
what happens to hbs if exposed to o2 for long period of time
distorts the red cell damaging the rbc membrane
sickle cell trait
one normal one abnormal b gene
HbAS
how many abnormal genees in sickle cell anemia
two
examples of other sickling disorders
HbS/β thalassaemia
HbSC disease; milder, but increased risk of thrombosis
what is sickle vaso occlusion
a sickle crisis
blockage or restriction of blood flow in blood vessels cused by sickle shaped red blood ells
precipitants of 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) chest crisis or (brain)stroke to rapidly reduce proportion of HbS in blood
long term management of sickle cell disease
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 investigations
- Bloods - FBC, Hb, red cell indices, blood film
- High performance liquid chromatography (HPLC) or electophoresis to quantify haemoglobins present
