Haemoglobinopathy Flashcards
Describe the structure of haemoglobin
Tetramer
4 globin chains
One haem group attached to each globin chain
What are the 3 main forms of haemoglobin?
HbA: (2-alpha, 2-beta)
HbA2: (2-alpha, 2-delta)
HbF: (2-alpha, 2-gamma)
The genes making the alpha protein for haemoglobin are located on which chromosome? How many alpha genes are on each chromosome?
Chromosome 16
2 alpha genes per chromosome
The genes making the beta protein for haemoglobin are located on which chromosome? How many beta genes are on each chromosome?
Chromosome 11
1 beta gene per chromosome
Which type of haemoglobin - HbA, HbA2 or HbF - is found in a foetus?
HbF
When does foetal haemoglobin typically reach adult level following birth?
6-12 months
What are haemoglobinopathies?
Hereditary conditions affecting globin chain synthesis
What inheritance pattern do haemoglobinopathies generally follow?
Autosomal recessive
What are the 2 main groups of haemoglobinopathies?
Thalassaemias
Structural variant
What is the problem in thalassaemias?
Decreased rate of globin chain synthesis, resulting in less haemoglobin
What is the problem in structural variant haemoglobinopathy?
Normal production of structurally abnormal globin chains, resulting in variant haemoglobin
Alpha thalassaemia (affecting alpha-chain synthesis) results from deletion of how many - one or both - alpha genes from chromosome 16?
Either! Can arise due to deletion of one alpha gene or both alpha genes
What are the 3 classifications of alpha thalassaemia?
Trait: 1 or 2 genes missing
HbH: 1 alpha gene left
Bart’s hydrops fetalis: no alpha genes
Alpha thalassaemia trait is usually asymptomatic. True/False?
True
Mild anaemia and may be mistaken for iron deficiency
Describe the clinical features of HbH alpha thalassaemia
Anaemia Very low MCV Splenomegaly Jaundice Growth retardation
What can be seen on special staining of red cells in HbH alpha thalassaemia?
Red cell inclusions (HbH bodies)
Describe the clinical features of Bart’s hydrops fetalis alpha thalassaemia
Severe anaemia (can't make Hb) Cardiac failure Oedema Growth retardation Hepatosplenomegaly Skeletal abnormality Death in utero
Beta thalassamia only affects beta chains, thus which type of haemoglobin production is affected?
Only affects HbA production
What type of mutations are typical in alpha and beta thalassaemias respectively?
Alpha thalassaemia typically due to deletions
Beta thalassaemia typically due to point mutations
What are the 3 classifications of beta thalassaemia?
Trait: no or 1 gene missing
Intermedia: 1 gene missing
Major: 2 genes missing
What are the laboratory features of beta thalassaemia major?
Very low MCV
Microcytosis, hypochromia
Anisopoikilocytosis
Target cells
Beta thalassaemia major is transfusion dependent. True/False?
True
Severe thalassaemia can cause extramedullary haematopoiesis. What are the consequences of this?
Hepatosplenomegaly
Skeletal changes
Organ damage
Cord compression
What becomes the main cause of mortality from transfusion treatment for beta thalassaemia major?
Iron overload
How can iron overload secondary to transfusion be managed?
250mg of iron per unit of red cells
Iron-chelating drug (desferrioxamine)
What is the best method of diagnosing thalassaemia? What does it show?
High performance liquid chromatography (HPLC)
Quantifies Hb present and identifies abnormal Hb
What is the pathophysiology of sickle cell disorder?
Point mutation in codon 6 of beta-globin gene, causing valine production instead of glutamine, altering the structure of Hb to produce HbS
What is the genetic makeup of sickle-cell trait?
One normal beta gene, one abnormal beta gene
Is sickle cell anaemia autosomal dominant or recessive?
Autosomal recessive
Requires 2 abnormal beta genes
What is a sickle crisis?
Episodes of tissue infarction due to vascular occlusion by sickle cells
List some precipitants of a sickle crisis
Hypoxia Dehydration Infection Cold exposure Stress Fatigue
Outline treatment of a sickle crisis
Opiate analgesia Hydration Rest Oxygen Antibiotic if infection Red cell transfusion if severe
What long-term treatment may be given for sickle cell disorder?
Penicillin if hyposplenism
Folic acid (increase RBC turnover)
Hydroxycarbamide (induce HbF production)
