haemoglopathies

• What are haemoglobinopathies?

  Genetic disorders affecting haemoglobin structure or production
• How many categories are haemoglobinopathies classified into?

  2 categories
• What is the difference between structural abnormalities and thalassemias in haemoglobinopathies?

  Structural abnormalities alter haemoglobin molecule; thalassemias reduce globin chain quantity
• What is the composition of normal haemoglobin?

  2 alpha and 2 beta chains

  
• What is the composition of abnormal haemoglobin?

  4 identical polypeptides
• What does each haemoglobin chain associate with?

  A heme group containing an iron atom
• How many normal beta genes does an individual have?

  2 normal beta genes
• How many normal alpha genes does an individual have?

  4 normal alpha genes
• On which chromosome is the α-globin gene cluster located?

  Chromosome 16
• On which chromosome is the β-globin gene cluster located?

  Chromosome 11
• What does the ζ-globin gene encode?

  Embryonic α-globin
• What does the ε-globin gene encode?

  Embryonic globin
• What do the γ-globin genes encode?

  Fetal globin
• What does the δ-globin gene encode?

  Adult globin
• What is hereditary persistence of fetal haemoglobin?

  Condition where HbF continues to be produced after birth
• What are the two major groups of thalassemia?

  α-thalassemia and β-thalassemia
• What happens in α-thalassemia?

  α-globin chains are deficient, β chains are in excess
• What happens in β-thalassemia?

  β-globin chains are deficient, α chains are in excess
• What is the pathophysiology of β-thalassemia?

  Excess α-globin chains form homotetramers that precipitate and damage RBC membranes
• What are the clinical phenotypes of β-thalassemia?

  Cooley's anemia
• What are the symptoms of Cooley's anemia?

  Pallor, hepatosplenomegaly, failure to thrive
• What is the blood profile of Cooley's anemia?

  Severe anemia, hypochromic RBCs, microcytic RBCs
• What is the management of thalassemia major?

  Blood transfusion and iron chelation
• What are the complications of iron overload in thalassemia major?

  Cardiomyopathy, liver fibrosis, endocrine dysfunction
• What causes α-thalassemia?

  Unequal crossing over between α1 and α2 genes
• What is sickle cell disease?

  Inherited disease where RBCs become crescent-shaped
• What is the pathophysiology of sickle cell disease?

  Single amino acid substitution in β-globin chain
• What is the amino acid substitution in sickle cell disease?

  Glutamic acid to valine
• What happens to hemoglobin S when deoxygenated?

  Forms insoluble fibers causing RBC deformation
• What are the two main types of bleeding disorders?

  Hemophilia A and Hemophilia B
• What causes Hemophilia A?

  Mutations in F8 gene encoding clotting factor VII

  
• What causes Hemophilia B?

  Mutations in F9 gene encoding clotting factor IX
• Why is Hemophilia A an X-linked disease?

  Mutations are carried on the X chromosome
• What is the prevalence of Hemophilia A in males worldwide?

  1 in 5000-10,000 males
• What are the complications of Hemophilia A?

  Recurrent bleeding into joints, muscles, and CNS
• What is the treatment for Hemophilia A?

  Factor VIII concentrates
• What was a complication of donor-derived factor VIII?

  Contamination by viruses
• What was the impact of factor VIII concentrates on Hemophilia A?

  Increased median age of mortality from 20 to 68 years
• How was the issue of virus contamination in factor VIII addressed?

  Heat treatment to kill HIV and hepatitis B virus
• What is the risk associated with abnormalities in blood coagulation?

  Increased risk of thrombosis