Thalassemia

major
CBL 4th year
Dr Sara khan
Dr Shumaila naz
 Case
 Miss xyz , a bride to be, with mild anemia
since childhood was to proceed abroad with
her in laws.

 During medical checkup for visa, her blood

picture revealed hypochromic microcytic cells
with low MCV and MCH.

 The embassy doctor ordered a test on basis

of which she was diagnosed as a case of
thalassemia trait.
 Her parents were called for counseling and
were told that certain blood tests should be
conducted in her husband to be, so as to
avoid thalassemia major in her off springs.
 However the family was not ready to go for
testing.
 After one year of marriage she gave birth to
a baby boy, by 6 months of age her baby
presented in pediatric clinic with complains of
failure to thrive, breathlessness on crying and
irritability.
 And at the age of 1.5 year that baby again
presented with features of severe anemia.

 On examination baby was anemic and

jaundiced with enlarged spleen.

 Blood picture showed microcytic

hypochromic anemia with anisocytosis and
poikilocytosis.
 Questions
1. What is the likely diagnosis of baby?
2. Which of the hemoglobin is raised in case
of thalasemia trait?
3. Which of the hemoglobin is raised in
cased of thalasemia major?
4. How the diagnosis of thalasemia is
made?
5. What advice would you give to the mother
for next pregnancy?
 Introduction
• Thalasemia syndromes are a
heterogenous group of disorder caused by
mutations that decrease the production of
adult hemoglobin.

• Endemic in the middle east , tropical africa

, the indian subcontinent and Asia.
Normal hemoglobin structure
 In adults
Type of hemoglobin Percentage

hemoglobin A 95% to 98%

hemoglobin A2 2% to 3%

hemoglobin F 1% to 2%

hemoglobin S 0%

hemoglobin C 0%
 Beta thalasemia
• Caused by mutations that decrease the
production of beta globin chains.

• thalasemia major is that in which both alleles

of gene are defective(b+/b+ or b0/b0)

• Thalasemia minor is that in which one allele

is defective and one is normal(b+/b or b0/b).
 Molecular pathogenesis
• Mutation in beta globin gene on
chromosome 11.
• The causative mutations are:
beta 0 mutations
beta+ mutations
• More than 100 different mutations.
• Individuals with two beta-thalasemia
alleles have severe anemia called beta
-thalasemia major.
 Pathogenesis
• Imbalance between alpha and beta
chains.
• Precipitation of unpaired alpha chain
leading to membrane damage.
• Ineffective erythropoiesis.
• Extra vascular hemolysis.
• Extra medullary hematopoiesis.
 Cont..
• Liver spleen and lymph nodes
enlargement.
• Excessive absorption of iron due to
ineffective erythropoiesis.
• Secondary hemochromatosis.

• Anemia is due to
•  decrease in HbA
• diminished survival of RBCs
 Signs and symptoms
• Severe anemia( transfusion dependent)
manifesting at the age of 6-9 months.
• Jaundice
• Skull and other bone deformities.(frontal
bossing)
• Maxillary enlargement (chipmunk facies)
• Hepato-splenomegaly
• Growth retardation.
Chipmunk facies
 Workup
• Labs for evidence of hemolysis(billirubin,
retic count, sr LDH ).
• Imaging x-ray skull showing hair on end
appearance.
• Peripheral blood smear.
• Hemoglobin analysis.
• Iron studies.
“Hair on end” appearance
Peripheral blood picture
 Hemoglobin analysis
• There are different techniques for it .these
are classified as protein based methods
which are
• Gel electrophoresis .
• HPLC
• CE
• IEF (iso-electric focusing )
 Other are DNA based test which are
performed in new born ,during pregnancy
for prenatal diagnosis
 PCR is used to amplify DNA then
genotyping is done
 Sample can be CVS ,mother peripheral
blood or amniotic cells .
 Treatment
• Treatment for patients of thalasemia major
includes:
• Long term transfusion therapy
• Iron chelation
• Splenectomy
• Allogeneic hematopoietic transplantation
• Supportive measures.