Makindo Medical Notes

Related Subjects: |Alpha Thalassaemia |Beta Thalassaemia |Anaemia of Chronic Disease |Aplastic anaemia(AML) |Autoimmune Haemolytic anaemia (AIHA)

Trait is common with a hypochromic microcytic anaemia with target cells and increased HbA2 on electrophoresis

About

• Inherited defect causing reduced production of beta-globin
• Fetal Hb has no Beta globin chains so there is no disease until HbF levels drop after birth.
• Defect in all Beta globin genes leads to Thalassaemia major
• Increase in HbA2 with 2 a and 2 d globin chains.
• There is an imbalance in globin chains

Epidemiology

• Asian, Arabic or Mediterranean origin

Aetiology

• In adults the Hb is composed of 2 a chains and 2 ß chains.
• In Beta Thalassaemia there is a defect in making Beta chains
• There are 2 genes per cell producing Beta chains
• Many gene mutations leading to variable Beta chain production
• There is haemolysis and ineffective erythropoiesis

Classification

• Thalassaemia major - severe requires transfusions lifelong. Iron overload.
• Thalassaemia intermedia - lifelong anaemia but fewer transfusion needs
• Thalassaemia minor - asymptomatic carrier

Clinical

• Extramedullary haemopoiesis leads to an expansion of bone marrow and hepatosplenomegaly. Skull marrow expansion leads to deformity which is often in the exams shown as a skull x-ray "hair on end appearance". Osteopenia.  
• Organ damage from Iron overload causes endocrine disease with pituitary, hypothyroidism and diabetes mellitus and hypogonadism as well as cardiac damage. Leg ulcers, gallstones, an aplastic crisis with intermedia
• Those with Beta thalassaemia trait may have problems during haemopoietic stress such as pregnancy and show mild anaemia and microcytosis

Investigations

• Microcytic hypochromic anaemia and target cells.. The MCV is much lower than would be expected.
• Raised reticulocyte count
• Raised HbA2, HbF and absent HbA ( a₂d₂ Hb on electrophoresis)
• Ferritin high with repeated transfusions

Management

• Transfusion to 9 to 10 g/dL- leads to Iron overload needing regular chelation therapy with desferrioxamine
• Splenectomy may reduce transfusion need
• Oral Folate is needed
• Large doses of Vitamin C helps excrete iron
• Haematopoietic cell transplantation for severe disease