9: Haemogobinpathies Flashcards
Hemoglobin
the major functional protein in red cells and carries oxygen throughout the circulation
Hemoglobin structure
a tetramer consisting of an alpha like globin chain and a beta like globin chain folded around a haem porphyrin center
what are the two main groups of inhertied disorders of hemoglobin
- disorders of hemoglobin structures
- disorders of hemoglobin synthesis, the thalassemia’s
during pre-natal life where does hematopoiesis happen
begins in the yolk sac, shifts to the liver, spleen and then bone marrow
during post-natal life where does erythropoiesis happen
primarily in the bone marrow
what are the two globin gene structures
alpha like cluster on chromosome 16
beta like cluster on chromosome 11
Clinical syndromes associated with structural Hb variants
- Haemolytic anaemia
- Cyanosis
- Polycythaemia
Haemolytic anaemia
unstable Hb
red blood cells are excessively fragile and break up causing anaemia and jaundice
cyanosis
blue colour to skin and mucous membranes
Hb releases oxygen but remains in reduced form
polycythaemia
excessive red blood cells which retain oxygen and do not release oxygen into tissues
sickle cell anaemia
- autosomal recessive disorder
- red blood cells become more fragile and break up
- chronic anemia sickling crisis due to blockage of small blood vessels with fragmented red cells
- common in west Africa, Caribbean and African Americans
treatment of sickle cell disease - acute crisis
pain relief
hydration
treatment of sickle cell disease - chronic management
vaccination
prophylactic antibiotics
blood transfusion
hydroxyurea
Thalassaemia
a group of genetic blood disorders when the body does not make enough hemoglobin which is a protein in red blood cells that carries oxygen
Alpha thalassaemia
caused by the underproduction of alpha globin from alpha globin gene cluster on chromosome 16
what does the severity of Alpha thalassaemia depend on
how many of the four genes are affected
beta thalassaemia
underproduction of beta globin gene on chromosome 11
where is alpha thalassaemia common
South East Asia
where is beta thalassaemia common
Mediterranean
what does the severity of Beta thalassaemia depend on
the nature of the gene mutations and whether one or both of the beta globin genes are affected
deletion of all four alpha globin genes - what condition does it cause
- causes condition called Hb Bart’s
- most severe form of alpha thalassemia
deletion of all four alpha globin genes - symptoms
babies with the condition are usually still born or die shortly after birth due to severe anaemia and heart failure
usually found in Asia
deletion of 3 alpha globin genes - what does it cause
Haemoglobin H disease
deletion of three alpha globin genes - why do the symptoms happen
People with Haemoglobin H disease only have one alpha globin that works properly.
To compensate for the lack of alpha chains the body starts to produce more beta chains, which form beta4 tetramers. These abnormal haemoglobins are less effective at transporting oxygen compared to normal haemoglobin.
deletion of three alpha globin genes - symptoms
jaundice
growth delays
anemia
deletion of two alpha globin genes
- alpha thalassemia
- mild, may not cause symptoms
- do not require blood transfusions
deletion of 1 alpha globin gene
- very mild condition
- individual still produces enough alpha globin genes to form functional hemoglobin molecules
what do repeated transfusions result in
premature death due to the complications of iron overload despite iron chelation therapy
alpha beta thalassemia
deletion of both the alpha and beta globin chains on chromosome 11
surprisingly mild amaemia due to compensatory increased production of gamma globin chains
