Haemoglobinopathies Flashcards
What are haemoglobinopathies
Inherited disorders where expression of one or more of the globin chains of Hb is abnormal
What are the categories of haemoglobinopathies
Abnormal Hb varients - mutations in genes for alpha or beta-globin chains alters stability and/or function of Hb
Thalassaemias - reduced or absent expression of normal alpha or beta-globin chains. Reduces level of Hb
What is sickle cell anaemia and what happen to RBCs in the disease
Is a autosomal recessive disorder which causes a valine to be exchanged for a glutamic acid at position 6 of beta-globin making Hb S more prone to polymerise at low O2
Hb polymers form under low O2 conditions resulting in deformation of the membrane, causing the sickle shape. Repeated episodes of sickling leads to irreversible damage to the membrane causing it to lose its elasticity so the RBC is less deformable
What are the consequences of sickle cell disease
Vaso-occlusive episodes/crises - occlusion of small capillaries by the sickled cells
Anaemia - sickled cells undergoing haemolysis so shortened lifespan
Jaundice and gallstones - increased bilirubin from chronic haemolysis
Splenic atrophy - splenic infarction. Increased suscepability to infection by encapsulated bacteria
Aplastic crises - bone marrow stops working
Haemolytic crises - greater loss of RBCs than production
What are the consequences of thalassaemias
Low Hb count causes hypochromic microcytic RBCs
Relative excess of other globin chain - defective nature of RBCs
Most maturing erythrocytes are destroyed in bone marrow and excessive destruction in spleen
What is beta-thalassaemia minor
Where only one beta-globin gene is mutated
Results in microcytosis but not anaemia as bone marrow produces more RBCs to increase Hb to normal
Anaemia only occurs in times of increased demand
What is beta-thalassaemia major
Occurs in homozygous individuals where both beta-globin genes mutate.
No beta-globin chain production and patient dependent on blood transfusions
What is alpha-thalassaemia trait
Where there is one or two affected genes causing mircocytosis and hypochomia
Minimal or no anaemia
What is hydrops fetalis
Where all four alpha genes malfunction resulting in death in utero due to absence of the alpha-globin chain
What is haemoglobin H disease
Where there is lack of function in 3 or 4 of the alpha-globin genes
Severe microcytosis, hypochromic anaemia, haemolysis and splenomegaly
What are three types of thalassaemia phenotypes and state what sort of transfusion is needed
Thalassaemia major - transfusion dependent
Thalassaemia intermedia - intermittent transfusion
Thalassaemia minor - no transfusion
What are the consequences of thalassaemia
Extramedullary haemopoiesis
Stimulation of EPO due to reduced O2 delivery
Iron overload due to excessive absorption and repeated transfusions
Reduced life expectancy
Treatments for thalassaemia
Transfusion of red cells
Iron chelation
Folic acid supplement
Immunisation
Holistic care
Stem cell transplants
