Thalassaemia Flashcards
Major form of adult haemoglobin
Alpha-2, beta-2 (HbA)
Main groups of haemoglobinopathies (2)
Thalassaemias- decreased rate of globin chain production
Structural haemoglobin variants- normal production of abnormal globin chains e.g. HbS
What pattern of anaemia do thalassaemias give rise to?
Microcytic hypochromic
How many copies of alpha globin genes does a normal person have?
Four copies (two genes)
Alpha-thalassaemias usually result from which kind of mutation?
Deletions of alpha genes
How many copies of the alpha gene need to be deleted for symptoms? What is this condition called?
Three. HbH disease
Features of HbH disease (3)
Microcytic anaemia
Splenomegaly
Jaundice due to haemolysis
What causes Barts hydrops fetalis?
Lack of any functional alpha genes (–/–)
Inheritance of HbH disease
Autosomal recessive
Management of HbH disease
Transfusion (mild- during illness, severe- transfusion dependent)
Folic acid supplementation
Diagnosis of alpha thalassaemia (4)
Suspected from red cell indices Blood film High performance liquid chromatography Haemoglobin electrophoresis PCR genotyping
Features of blood film in alpha thalassaemia (4)
Microcytosis
Hypochromia
Anisocytosis (abnormal variation in red cell size)
Poikilocytosis (presence of abnormally shaped RBCs)
Why is only HbA affected in beta thalassaemia?
Only Hb which has beta chains
What is beta thalassaemia caused by?
Autosomal recessive point mutations which either inactivate (B^0) or reduce function (B^+) of beta-globin
Classification of beta thalassaemia (3)
Trait- asymptomatic
Intermedia- requires occasional transfusion
Major- lifelong transfusion dependency
Diagnostic features of beta thalassaemia major (3)
Elevated HbA2
Film: microcytic, target cells, anisopoikilocytosis
HPLC- mainly HbF
Clnical features of beta thalassaemia major (4)
Aged 6-24 months
Failure to thrive
Pallor
Signs of extramedullary haematopoiesis
Signs of extramedullary haematopoiesis in beta thalassaemia major (3)
Hepatosplenomegaly
Bony deformities
Organ damage
Management of B-thal major
Regular transfusion programme to maintain Hb above 95-105g/l
Main cause of morbidity/mortality from treated B-thal major
Iron overload
Manifestations of iron overload
Cardiac- CCF,arrythmias
Liver cirrhosis, HCC
Endocrine dysfunction
Other complications of B-thal major
Tranfusion-related
Hypersplenism
Increased sepsis risk due to leucopenia
Management of iron overload in B-thal major
Iron chelating drugs such as desferrioxamine
Why is compliance poor with desferrioxamine?
Parenteral administration
Pathophysiology of sickle cell anaemia
Autosomal recessive specific point mutation in codon 6 of beta globin gene, creating Hb which polymerises at low [o2], distorting red cell membrane
Manifestations of sickle cell trait (2)
Usually asymptomatic
Spontaneous haematuria may occur due to microvascular renal infarction
Consequences of sickle cell anaemia
Tissue infarction due to vascular occlusion
Chronic haemolysis
Sequestration of RBCs in spleen/liver
Long-term treatment of sickle cell anaemia
Prophylactic penicillin Vacccination Folic acid Top-up and exchange transfusions Hydroxycarbamide
What does hydrocarbamide do?
Induces HbF production
