Haemoglobinopathies Flashcards
What are the genetics of sickle cell?
Autosomal recessive
When do symptoms from sickle cell appear?
4-6 months
HbSS takes over from HbF
What is the long term management of sickle cell?
Hydroxycarbamide - raises HbF levels
Exchange transfusion
Supportive
What are the types of sickle cell crisis?
Vaso-occlusive (painful)
Acute chest crisis
Aplastic
Sequestration
What precipitates vase-occlusive crises?
Infection
Dehydration
Altitude
Hypoxis
How are vast-occlusive crises diagnosed in sickle cell?
Clinical diagnosis
What is the pathophysiology of a chest crisis in sickle cell?
Vaso-occlusion in pulmonary microvasculature –> infarction in lung
What is seen on CXR in chest crisis?
Pulmonary infiltrates
What is the management of chest crisis?
Supportive - pain relief, antibiotics, oxygen
Transfusion - improves oxygenation
What is an aplastic crisis in sickle cell?
Sudden fall in haemoglobin due to parovirus suppressing bone marrow
What is seen on bloods in aplastic crisis?
Low Hb
Reduced reticulocyte count
What is a sequestration crisis in sickle cell?
Sickling within organs such as spleen or lungs causes pooling of blood with worsening of anaemia
What is seen on bloods in sequestration crisis?
Raised retics
What is alpha thalassaemia?
Deficiency of alpha chains in Hb
What are the genetics of alpha thalassaemia?
Affects 2 alpha globulin genes on chromosome 16
What determines the severity of alpha thalassaemia?
Number of alpha globulin alleles affected
What is the picture be on bloods if thalassaemia affected 1-2 alleles?
Microcytic and hypochromic but Hb normal
What s the picture on bloods if 3 alpha globulin alleles affected?
Hypochromic microcytic anaemia with splenomegaly
What is beta thalassaemia trait?
Some but not all beta globulin alleles affected
What is the characteristic picture on bloods of beta thalassaemia trait?
Mild hypochromic microcytic anaemia
Microsytosis normally disproportionate to anaemia
What is beta thalassaemia major?
Absence of beta globulin chains
What are the genetics of beta thalassaemia?
Autosomal recessive
Chromosome 11
What is the presentation of meta thalassaemia major?
Failure to thrive
Hepatosplenomegaly
Microcytic anaemia
Normally presents in first year of life
Raised HbA2 and HbF
What is the management of beta thalassaemia major?
Transfusion with iron chelation therapy
What is the pathophysiology of G6PD deficiency?
Decreased G6PD –> decreased NADPH –> reduced glutathione –> increased red cell sensitivity to oxidative stress
What is G6PD deficiency?
Glucose 6 phosphate deficiency
Most common red blood cell enzyme defect
What are the common features of G6PD deficiency?
Neonatal jaundice
Intravascular haemolysis
Gallstones
What is seen on blood film with G6PD?
Heinz bodies
Bite and blister cells
What is the inheritance of G6PD?
X linked recessiveWhat
population is G6PD normally seen in?
African or Mediterranean
What is the typical history of G6PD?
Neonatal jaundice
Gallstones
Drugs precipitate haemolysis
What drugs are associated with haemolysis in G6PD?
Anti-malarials - primaquine
Cipro
Sulphonamides, sulphasalazine, sulphonylureas
How is G6PD diagnosed?
G6PD enzyme assay - 3 months post acute episode to allow time to recover
What are the genetics of hereditary spherocytosis?
Autosomal dominant
What population is hereditary spherocytosis seen in?
Northern Europeans
What is the common presentation of hereditary spherocytosis?
Normally more chronic picture
Failure to thrive
Jaundice, gallstones, splenomegaly
What precipitated haemolytic crisis in hereditary spherocytosis?
Parvovirus infection
How is hereditary spherocytosis diagnosed?
Family history, typical clinical features and lab features
- spherocytes, raised relics, raised MCHC
What is used to diagnose hereditary spherocytosis if there is uncertainty?
EMA binding test
What kind of haemolysis is seen in hereditary spherocytosis?
Extravascualr - so gets splenomegaly
What kind of haemolysis is seen in G6PD?
Intravascular
