Haemoglobinopathies Flashcards
What is the structure of Hb?
Tetramer made up of 2 alpha globin and 2 beta globin chains
1 haem group attached to each globin chain
What are the 3 major forms of Hb?
HbA (2 alpha 2 beta)
HbA2 (2 alpha 2 delta)
HbF (2 alpha 2 gamma)
Which chromosomes are alpha like geneson?
Chromosome 16
What chromosome are beta like genes on?
Chromosome 11
At what age are adult levels of Hb reached?
6-12 months
What are haemoglobinopathies?
Hereditary conditions affecting globin chain synthesis?
What is the difference between the 2 main groups of haemoglobinopathies?
Thalassaemias (decreased rate of globin chain synthesis)
Structural Hb variants (normal production of structurally abnormal globin chains)
What are the 2 types of thalassaemias?
Alpha & Beta
How do thalassaemias affect normal physiology?
Inaequate Hb production (microcytic hypochromic anaemia)
Unbalanced accumulation of globin chains (ineffective erythropoiesis & haemolysis)
How are alpha thalassaemias classified?
a thal trait (1 or 2 genes missing) HbH disease (only 1 alpha gene left) Hb Barts hydrops fetalis (no functional alpha genes)
How can alpha thal trait be distinguished from iron deficiency?
alpha thal - normal ferritin & red blood cell count raised
How would HbH disease present on FBC?
Anaemia with very low MCV and MCH
How does HbH disease look on a blood film?
Excess B chains form tetramers called HbH wich cannot carry oxygen
HbH bodies can be seen with special stains
Clinical features of HbH disease
Splenomegaly
Jaundice 9aemolysis & ineffectiveerythropoiesis)
Can present from mild anaemia to transfusion dependent
Clinical features of Hb Bart’s Hydrops fetalis syndrome
Severe anaemia Cardiac failure, oedema Growth retardation Severe hepatosplenomegaly Skeletal and CV abnormalities Most dieinutero
Clinical features of B thalassaemia
Presents aged 6-24 months
Failure to thrive
Pallor
Extramedullary haematopoiesis (hepatosplenomegaly, skeletal changes, organ damage
Management of B thal major
Lifelong transfusion programme
What is the main cause of mortality for patients being treated for B thal major?
Iron overload
What are the endocrine consequences of iron overload?
Impaired growth and pubertal development
Diabetes
Osteoporosis
What are the cardiac complications of iron overload?
Cardiomyopathy Arrhythmias
How is iron overload treated?
Iron chelating drugs (Desferrioxamine) -binds toron and are excreted in urine or stool
Why are patients being treated for B thal major at higher risk of bacterial sepsis?
Because they can have iron overload and bacteria like iron
How can thalassaemias be diagnosed?
Blood film (hypochromia, target cells, anisopoikilocytosis0 HPLC (quantifies different types of Hb)
What is the pathophysiology of sickling disease?
Point mutation in codon 6 ofthe B globin gene - alters structure of resulting Hb (HbS)
HbS polymerises if exposed to low oxygen levels for a prolonged period
Distorts the red cell damaging the RBC membrane
