Thalassemia

1. Thalassemia
Muhammad Ariff Mahdzub

2. Case scenario
• Affina 13 Month, Female who live at Balok came ed due to Difficulty
in breathing 5 day and Pallor -1month
• On examination, patient looks fatique, jaundice and palpitation.
Respiratory rate increase.

3. On Investigation
Fbc :
-Haemoglobin : 6g/dl (anemia)
Complete blood count test
-MCV show microcytic
-MCH shows hypocromic
Serum Ferritin test: Normal (rule-out Iron def.)

4. Conformation Test
• Peripheral Film: Fragmented cells, targeted cell
• Hemoglobin
-Hb A2--------------3.9% (high)
-Hb F ---------------96.1% (high)

6. • Increased red cell destruction ( hemolysis)
• Red cell membrane disorder hereditary spherocytosis
• Red cell enzyme disorder glucose-6-phosphate
dehydrogenase deficiency
• Immune autoimmune hemolytic anemia
• Haemoglobinopathies thalassemia, sickle cell disease

7. Haemoglobinopathies
• These are red blood cell disorder which cause hemolytic anemia because of reduced or
absent production of HbA
• Alpha-thalassemia - cause by deletion or mutation (occasionally) in the a-globin gene
• Beta-thalassemia - cause by mutation in b-globin gene
• sickle B-thalassemia – affected children inherit HbS from one parent & B-thalassemia
from other
• Clinical manifestation of the hemoglobinopathies affecting the b-chain are delayed until
6 months of age when most of the HbF present at birth have been replaced by adult HbA

9. Beta thalassemias
• Occur most often in people from the indian subcontinent,
Mediterranean, and middle east.
• 2 main type and both are characterized by a severe reduction in the
production of B-globin.
• B-thalassemia major – most severe form of the disease, HbA (a2b2)
cannot be produced because of the abnormal B-globin gene
• B-thalassemia intermedia – this form is milder and of variable
severity. The B-globin mutation allow a small amount of HbA and
large amount of HbF to be produced

11. Clinical features
• Pallor (anemia)
• Jaundice
• Failure to thrive
• Bossing of the skull
• Maxillary overgrowth
• In absence transfusion, may
develop Hepatosplenomegally
• Transfusion dependent

12. Management
• May be Fatal without regular blood transfusion
• Lifelong monthly transfusion
• The aim – to maintain hemoglobin concentration above 10g/dl in
order to reduce growth failure and prevent bone deformation
• Life long repeated blood transfusion come with complications
• For these reasons, all patient are treated with iron chelation with
subcutaneous desferrioxamine or oral iron chelator drug deferasirox
• iron chelation therapy start from 2-3 years age
• Alternative treatment is for b-thalassemia major is bone marrow
transplantation.
• splenectomy- - hypersplenism

13. Complication of long-term blood transfusion
Iron deposition- the Most important
-heart – cardiomyopathies
-Liver – cirhossis
-Pancreas – diabetes
-Pituitary gland – delayed growth and sexual maturation
-Skin – hyperpigmentation
Antibody formation (10%)
-Allo–antibodies to transfused red cells in the patient make finding compatible blood very
difficult
Infection less 10%
-Hepatitis A,B,C
-HIV
-Malaria
-prions

14. Venous access (common problem)
-Often traumatic in young children
-Central venous access device (eg: portacath) maybe required. These
device may prone to infection

15. Alpha- thalassemia
• The manifestation of alpha-thalassemia depend on the number functional of alpha-globin gene
• Most severe form a-thalassemia is Hb Barts hydrop fetalis
• Cause by deletion all four a-globin gene so no HbA
• Present in mid trismester with fetal hydrop (edema and ascites) from fetal anemia
• Fatal in utero or within hour of delivery

16. • When only 3 of the alpha-globin are deleted, its called HbH disease.
• Mild- moderate anemia
• Some patient is transfusion dependent
• Deletion 1 or 2 alpha-globin (thalassemia trait)
• Asymptomatic
• Anemia is mild or absent
• Red cell might be hyporchromic and microcytic, cause confusion with iron deficiency