Haemoglobinopathies Flashcards
what might be the cause of haemoglobinopathies be and can you provide examples?
- usually inherited typically autosomal recessive.
- abnormal globin chain variants with altered stability or function eg: sickle cell.
- reduced or absent expression of normal globin chains eg: thalessaemias.
describe the structure of haemoglobin.
- tetramer of 4 globin pp-chains ; 2 alpha and 2 non alpha (beta, gamma or sigma).
- each globin chain complexed with oxygen binging to haem group.
what is the significance and structural differences of different types of haemoglobin ( fetal vs HbA ) ?
- HbF composed of 2alpha + 2gamma globin chains more common before birth.
- HbA commences before birth and steadily becomes more dominant after birth. (2a +2B)
- globin proteins from different genes combine to from different Hb tetrameres.
describe the relationship between globin types and genes on chromosomes.
- alpha globin gene (2of them) complex is on chromosome 16 and beta on chromosome 11.
- humans have 4 alpha-globin genes as 2 from each parent and 2 beta-globin genes.
why does Thalassaemia develop?
- disruption to the regulation of expression of globin genes affecting 1:1 ratio of alpha to non alpha globin chains.
depending on the amount of alpha-genes affected the severity and range of symptoms vary. differentiate.
- 1 gene : asymptomatic carrier.
- 2 genes : alpha-thalassaemic trait.
- 3 genes : HBH disease with tetramers of B-globins.
- 4 genes : hydrops fetalis where excess gamma-globin so unable to deliver O2 in foetus.
beta-thalassaemia can be minor, intermedia or major. how are they different?
- minor : heterozygous, usually asymptomatic with traits of hypo-chromic and microcytic RBC.
- intermedia : severe anaemia, HBH similar, genetically heterogenous.
- major : transfusion dependent, manifests 6-9 months after birth, homozygous.
what might a blood smear of patient with severe thalassaemia show?
- hypochromic and microcytic red cells dur to low HB.
- anisopoikilocytosis with target cells, nucleated RBC and heinz bodies.
how does the unaffected globin chain contribute to complications in individuals with thalassaemia?
- insoluble aggregates of unaffected chains.
- Hb aggregates and gets oxidised resulting in premature death of erythroid precursors within BM, excessive destruction by spleen so haemolytic anaemia.
what are the consequences of thalassaemia?
- extra-medullary haemopoiesis to compensate, impairs growth and causes classical skeletal abnormalities
- splenomegaly.
- reduced O2 delivery, EPO stimulated but makes more defective cells (expanded to extra-medul).
- iron overload as excessive absorption due to ineffective haematopoiesis, repeated transfusions.
- reduced life expectancy.
what are the treatments for thalassaemia?
- red cell transfusion.
- iron chelation to delay overload.
- folic acid to help erythropoiesis.
- holistic care to manage complications.
- stem cell transplant to replace defective red cell prod.
- pre-conception counselling.
what is sickle cell disease?
- autosomal recessive disease resulting from mutation of B-globin gene where glutamic acid replaced with valine.
- HbS which exists as tetramers under normal O2 tension forms polymers at low O2 tension causing sickle shape which becomes irreversible with repeat.
what are the 3 main crises occuring with sickle cell disease?
- vaso-occlusive.
- aplastic.
- haemolytic.
what are the treatments for sickle cell disease?
- folic acid.
- penicillin and vaccinations to protect immunity as most hyposplenic.
- Hydroxycarbamide to increase HbF.
- red cell exchange.
why might haemolytic anaemia develop?
differentiate acquired vs inherited causes.
- if rate of destruction exceeds production rate.
- inherited (more fragile) : G6PDH deficiency, pyruvate kinase deficiency, hereditary spherocytosis, sickle.
- acquired (damage) : mechanical, antibody, oxidant, heat, enzymatic damage.
