Thalasemia

1. Thalassemia
• Thalassemia sydromes are a
heterogenous group of inherited
anemias
characterised by reduced or absent
synthesis of either alpha or Beta globin
chains of Hb A

2. BASICS - 3 types of Hb
• 1. Hb A - 2 α and 2 β chains forming a tetramer
• • 97% adult Hb
• • Postnatal life Hb A replaces Hb F by 6 months
• 2. Fetal Hb – 2α and 2γ chains
• • 1% of adult Hb
• • 70-90% at term. Falls to 25% by 1st month and
progressively
• 3. Hb A2 – Consists of 2 α and 2 δ chains
1.5 – 3.0% of adult Hb

3. Classification
• If synthesis of α chain is suppressed – level of
all 3 normal Hb A (2α ,2β),A2 (2α ,2 δ),F(2α ,2γ)
is reduced – alpha thalassemia
• If β chain is suppressed - adult Hb is
suppressed - beta thalassemia

4. Pathophysiology of alpha thalasemia
Alpha thalassemia results when there is
disturbance in production of α-globin from
any or all four of the α-globin genes.
Genes are responsible for regulating the
synthesis and structure of different globins
which are divided into 2 clusters.
The α-globin genes are encoded on
chromosome 16
The γ, δ, and β-globin genes are encoded on
chromosome 11

6. Clinical Presentation
• Shortage of red blood cells- Anemia
• Pale skin
• Weakness
• Fatigue
• Enlarged liver and spleen-
hepatosplenomegaly

7. • Heart defects
• Abnormalities of the urinary system or
genitalia
• Hb Bart syndrome can cause complications in
pregnancy such as
• High blood pressure
• Premature delivery
• Abnormal bleeding
• Jaundice

8. Treatment of Alpha Thalassemia
• Treatment for thalassemia often involves
regular blood
transfusions and folate supplements.
• Persons who receive significant numbers of
blood transfusions need a treatment called
chelation therapy to remove excess iron from
the body.
• Bone marrow transplant may help treat the
disease in some patients, especially children

9. • Surgical Treatment
• – Perform splenectomy if transfusion
requirements are increasing.
• Medications
• • FOLIC ACID- ORAL
• • FOLIC ACID - INJECTION
• • DEFEROXAMINE - INJECTION

10. Beta Thalassemia
• Specifically, it is
characterized by a
genetic deficiency in the
synthesis
of beta- globin chains.
• Beta-globin is a
component
(subunit) of hemoglobin

11. Beta Thalassemia
• Deficient/absent beta subunits
• Commonly found in Mediterranean, Middle
East, Asia, and Africa
• Three types:
• Minor
• Intermedia
• Major (Cooley anemia)
asymptomatic at birth as HbF functions

12. GENETIC BASIS OF BETA THALASSEMIA
• Encoding genes on chromosome 11 (short arm)
• Each cell contains 2 copies of beta globin gene
• beta globin protein level = alpha globin protein level
• Suppression of gene more likely than deletion
• 2 mutations: beta-+-thalasemia OR beta-0-thalasemia
• “Loss” of ONE gene thalassemia minor (trait)
• “Loss” of BOTH genes shows complex picture
• 2 beta-+-thal:
thalassemia intermedia / thalassemia major
• 2 beta-0-thal:
thalassemia major
• Excess of alpha globin chains

14. PATHOPHYSIOLOGY
• Disturbance of ratio between Alpha & non alpha
globin chain synthesis then absent or decrease
production of one or more globin chains
• Formation of abnormal Hb structures
• Ineffective erythropoiesis
• Excessive RBCs Destruction
• Iron Overload
• Extra-medullary hematopoiesis

15. SIGNS & SYMPTOMS
Beta Thalassaemia Minor :
• Usually no signs or symptoms except for a mild persistent
anemia not responding to hematinics.
BetaThalassaemia Major : manifests after 6 months
• 1. Pallor- fatigue, irritability
• 2. Growth retardation.
• 3. Recurrent infections
• 4. Bony abnormalities specially of the facial bones,
hemolytic facies, caput quadtratum
• 5. Enlarged spleen and liver.
• 6. Delayed sexual development
• 7. Features of complications .

16. Treatment
• Treatment for beta thalassemia involves iron
chelation.
• 1. Deferoxamine
• 2. Deferasirox
• Deferoxamine is an intravenously administered
chelation agent.
• Desferal (deferoxamine) chelates iron by forming
a stable complex that prevents the iron from
entering into further chemical reactions. It readily
chelates iron from ferritin and hemosiderin but
not readily from transferrin.

17. Surgical Treatment
• Splenectomy- decreases transfusion
requirements
• Cholecystectomy- Patients with thalassemia
minor may have bilirubin stones in their
gallbladder and, if symptomatic, may require
treatment. Perform a cholecystectomy using a
laparoscope or carry out the procedure at the
same time as the splenectomy.

18. IMMUNIZATION PRIOR TO
SPLENECTOMY
• Pneumcoccal vaccine. 0.5 ml SC
• If child has received a complete primary course PLUS
• a single booster dose
• Age<2 years: ( give one dose PCV13 Prevenar13 )
• Age > 2years: ( give one dose PPV 23 Pneumovax 23
• revaccinate after 3 years )
• If child has not recieved primary course
• Age 16 months – 5years : give two doses PCV13 Prevenar13
• 8 weeks apart
• If aged 5-18 years - one dose
• give one dose PPV 23 Pneumovax 23 at least 8 weeks after
the last PCV13 dose , revaccinate after 3 years.

19. • Meningococcal vaccine:
• Quadravalent meningococcal (Menactra) 0.5
• mL IM upper deltoid.
• o Children aged 2 through 6 years :Two doses of
• Menactra® at least 8 weeks apart, followed by a single
• booster dose 3 years later and then a single booster
• dose every 5 years
• Children aged 7 years and over and adults through
• 55 years :Two doses of Menactra® at least 8 weeks
apart, followed by a single booster dose every 5 years
• Haemophilus b conjugate : One dose regardless of
previous vaccination history

21. Hemoglobin D
The most common HbD variant, HbD-Los Angeles (HbD-
Punjab), is caused by a glutamic acid to glutamine
substitution at codon 121 of the beta globin gene .
Individuals with HbD trait (HbAD) are asymptomatic, not
anemic, and have normal red cell indices.
Homozygosity for HbD (hemoglobin D disease, HbDD) is
rare and is associated with only mild laboratory
abnormalities.
Inheritance of HbD together with HbS (ie, HbSD disease)
can result in severe disease with clinical manifestations
similar to homozygous sickle cell anemia.

22. SICKLE-HbD DISEASE
Although asymptomatic in the heterozygous form,
inheritance together with an HbS allele (HbSD
disease) can result in a severe disease with
clinical manifestations similar to homozygous
SCD.
There is moderately severe hemolytic anemia and
the peripheral smear shows marked anisocytosis
and poikilocytosis, target cells, and irreversibly
sickled cells. Some children have severe disease
similar to that of sickle cell anemia. However,
persistent splenomegaly is more common.

23. • There are five subtypeshemoglobins, Hb D-
Chicago, Hb D-North Carolina, Hb D-Punjab,
Hb D-Portugal and Hb D-Oak Ridge and found
that all exhibited the same chemical
composition as the first one discovered, Hb D-
Los Angeles.The most frequent denominations
for this mutant hemoglobin found in the
literature are Hb D-Los Angeles or Hb D-
Punjab