Haemoglobinopathy Flashcards
HbA?
2 alpha
2 beta
HbA2?
2 alpha
2 delta
HbF?
2 alpha
2 gamma
What chromosome are alpha genes on?
16
2 genes per chromosome
What chromosome are beta genes on?
11
One gene per chromosome
What is the pattern of inheritance for haemoglobinopathies?
Autosomal recessive
What is a thalassaemia?
Reduced glob in chain synthesis, leads to impaired haemoglobin production
Two types of thalassaemia?
Alpha
Beta
Alpha thalassaemia is a result of what?
Mutations affecting alpha globin chain synthesis
The 3 types of alpha thalassaemia?
Trait
HbH disease
Hb Barts hyrops fetalis
Gene situ in alpha thalassaemia trait?
One or two genes missing
Gene situ in HbH disease ?
Only one alpha gene left
Gene situ in Hb Barts hydrops fetalis ?
No functional alpha genes
How do you distinguish alpha thalassaemia trait from iron deficiency?
Normal ferritin
What happens to the excess beta chains in HbH disease?
The form tetramers which cannot carry oxygen
Treatment of severe HbH disease?
Maybe need splenectomy +/- transfusion
Can any HbA be made in Hb Barts hydrops fetalis?
No
Beta thalassaemia is the result of what?
Disorder of beta chain synthesis
What types of haemoglobin are affected in beta thalassaemia?
Only HbA as it is the only Hb that contains beta chains
Which is the worst thalassaemia to have?
Alpha because it affects all types of haemoglobin - cannot substitute loss of HbA by making more of another
When does beta thalassaemia major tend to present?
6-24 months old
Why does beta thalassaemia major present at 6-24 months old?
Reduction in HbF so when trying to make HbA, realises there is a disorder in making the beta chains
Haemoglobin analysis in beta thalassaemia major?
Mainly HbF
Minimal HbA
Management of beta thalassaemia major?
Regular transfusion
Bone marrow transplant if be for complications develop
Features of extramedullary haematopoiesis?
Hepatosplenomegaly
Skeletal changes
Organ damage
Consequences of iron overload - endocrine
Impaired growth and pubertal development
Diabetes
Osteoporosis
Consequences of iron overload - cardiac
Cardiomyopathy
Arrhythmias
Consequences of iron overload - liver
Cirrhosis
Hepatocellular cancer
Management of iron overload?
250mg of iron per unit of red cells
Iron chelating drugs - eg desferrioxamine
How do iron chelating drugs manage iron overload?
Chelators bind to iron -> complexes form -> excreted in urine or stool
What is the pathophysiology of sickling disorder?
Point mutation in codon 6 of beta globin gene - substitutes glutamine to valine -> Bs
Alters Hb -> HbS
HbS polymerises if exposed to low O2 -> distorts red cell, damaging RBC membrane
Types of sickling disorder?
Sickle trait (HbAS) Sickle cell anaemia (HbSS)
What happens in sickle cell trait?
One normal and one abnormal beta gene
Asymptomatic
Mainly HbA / <50% HbS
What happens in sickle cell anaemia?
Two abnormal beta genes No HbA Sickle crisis Chronic haemolysis Hypospelnism due to repeated infarcts
What happens in sickle crisis?
Sickle cell vaso-occlusion -> tissue ischaemia and sever pain
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 if severe
Long term management of sickle crisis?
If hyposplenism- prophylactic penicillin and vaccinations to reduce risk of infection
Folic acid supplementation
Hydroxycarbamide can reduce severity of disease by inducing HbF production
