THALASSAEMIA

HIBA
18Q0856
 THALASSAEMIA:

• Thalassemia is an inherited blood disorder characterized

by less oxygen-carrying protein (hemoglobin) and fewer
red blood cells in the body than normal.
It is an autosomal recessive disorder characterized by
reduction in the synthesis of globin chain( alpha and beta).
Reduced globin chain synthesis causes reduced hemoglobin
synthesis.
• The hallmark laboratory features are low MCV and low MCH,
elevated reticulocyte ( immature RBC).

TYPES OFTHALASSEMIA
ALPHA THALASSAEMIA:
BETA THALASSEMIA
 ALPHA THALASSEMIA:

• Alpha thalassemia is a result of changes in the

genes for the alpha globin component of
hemoglobin.

ETIOLOGY:
Mutation in the DNA of cells that produce
hemoglobin.
There is either no alpha chain production or reduced
production of chain.
Inheritance.
• 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 and the
γ, δ, and β-globin genes are encoded on chromosome 11
A normal person carries a linked pair of alpha globin genes, 2
each from maternal and paternal chromosome.
Therefore, alpha thalassemia occurs when there is a
disturbance in production of α-globin from any or all four of
the α-globin genes.
 PATHOPHYSIOLOGY:
When functional point mutations, frame shift mutations, nonsense
mutations, and chain termination mutations occur within or around the
coding sequences of the alpha-globin gene cluster hemoglobin is
impaired.

When that occurs, protein synthesis may be inhibited

Normal production of alpha chains is absent which results inexcess
production of gamma- globin chains in the fetus and newborn or beta-
globin chains in children and adults.
The β-globin chains are capable of forming soluble tetramers (beta-4, or
HbH)
This form of hemoglobin is still unstable and precipitates within the
cell, forming insoluble inclusions called Heinz bodies.
These Heinz bodies damage the red blood cells.
This further results in damage to erythrocyte precursors and
ineffective
erythropoiesis in the bone marrow, hypochromia and microcytosis of
circulating red blood cells.
 CLINICAL PRESENTATION:

Pale skin
Weakness
Fatigue
Enlarged liver and spleen- hepatosplenomegaly
 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
 TREATMENT :-
• Treatment for thalassemia often involves regular
blood transfusions and folate supplements through
food.
• If you receive blood transfusions, you should not take
iron supplements. Doing so can cause a high amount
of iron to build up in the body, which can be harmful.
• 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.
• Perform splenectomy if transfusion requirements are
increasing.
 PHARMACOLOGICAL THERAPY:
Patient with mild thalassemia requires no treatment and should
be identified so that they will not be subjected to repeated
evaluation and treatment for iron deficiency.
FOLIC ACID will be given orally or intravenously
– Folic acid is the man-made form of folate which is a B6- vitamin
naturally found in some foods.
– It is needed to form healthy cells, especially red blood cells.
• Dosage : Taken orally with or without food once daily.
• However, recommended dose for deficiency states
is 250-1000 mcg (micrograms) per day.
• In IV 1- 5 mg once per day.
DEFEROXAMINE INJECTION: Deferoxamine is an iron-binding agent
that belongs to a class of drugs known as heavy metal antagonists. It
works by helping the kidneys and gallbladder get rid of the extra iron
• This medication is not recommended for use in children less
than 3 years old.
• This medication is administered via IM, IV or SC.
• Intramuscular Administration: A dose of 1000 mg should
be administered initially. This may be followed by 500 mg
every 4 hours for two doses. Depending upon the clinical
response, subsequent doses of 500 mg may be administered
every 4-12 hours. The total amount administered should not
exceed 6000 mg in 24 hours.
• Subcutaneous Administration: A daily dose of 1000-2000
mg/day should be administered over 8-24 hours, utilizing a
small portable pump capable of providing continuous mini-
infusion. The duration of infusion must be individualized. In
some patients, as much iron will be excreted after a short
infusion of 8-12 hours as with the same dose given over 24
hours.
• Intravenous Administration
• This may be followed by 500 mg over 4 hours for
two doses. Depending upon the clinical response,
subsequent doses of 500 mg may be administered
over 4-12 hours. The total amount administered
should not exceed 6000 mg in 24 hours.
• As soon as the clinical condition of the patient
permits, intravenous administration should be
discontinued and the drug should be administered
intramuscularly
 BETA THALASSAEMIA:

Beta thalassemia is a genetic blood disorder that reduces the

production of hemoglobin. Hemoglobin is the iron containing
protein in red blood cells that carries oxygen to cells
throughout the body.
Specifically, it is characterized by a genetic deficiency in the
synthesis of beta- globin chains.
Beta-globin is a component (subunit) of hemoglobin.
Beta thalassemia usually caused by point mutation
rather than deletion.
 TYPES :
Beta Thalassemia Beta Thalassemia
Major (Cooley's
anemia) Minor
- severe form of - presence of one
beta thalassemia normal gene and
- presence of two one with a mutation
abnormal genes that - causes mild to
cause either a severe moderate
decrease or mild anemia.
complete lack of
beta globin
production
 ETIOLOGY:
• Beta thalassemia is caused by a deficiency of Beta globin
inherited in an autosomal recessive pattern, which means both
copies of the HBB(Hemoglobin beta) gene in each cell have
mutations.
• The parents of an individual with an autosomal recessive condition
each carry one copy of the mutated gene, but they typically do not
show signs and symptoms of the condition.
• The HBB gene provides instructions for making a protein called
beta-globin.
• When there is a mutations in the HBB gene, it prevents the
production of any beta-globin.
• The absence of beta-globin is referred to as beta- zero (B0)
thalassemia.
• Other HBB gene mutations allow some beta-globin to be produced
but in reduced amounts. A reduced amount of beta-globin is called
beta-plus (B+) thalassemia.
 CLINICAL PRESENTATION:

•Thalassemia minor- characterized by mild anemic symptoms.

• Symptoms of beta thalassemia major appear in the first two
years of life.
• Fatigue and weakness
• Pale skin or jaundice (yellowing of the skin)
• Protruding abdomen with enlarged spleen and liver
 Laboratory finding:

• Beta thalassemia minor: These patient have a modest

anemia with hematocrit between 28% to 40%. The MCV
ranges from 55fL to 75fL, and the red blood cell count is
normal or increased. The reticulocyte count is normal or
slightly elevated. The peripheral blood smear is mildly
abnormal with hypochromia, microcytosis and target
cells.
• Beta thalassemia major: These patients have severe
anemia and without transfusion the hematocrit may fall
to less than 10%. Little or no Hb A is present. Variable
amount of hemoglobin is seen.
 TREATMENT:
• Patient with mild thalassemia require no treatment and should
be identified so that they will not be subjected to repeated
evaluation and treatment of iron deficiency.
• Beta thalassemia minor: It is the mildest form. It may not
require any treatment. For a mild anemia folic acid can help.
Folic acid is a vitamin B that raises the number of red blood
cells that your body makes. In certain condition adult may
require blood transfusion.
• Beta thalassemia major: If the patient having beta
thalassemia major, patient need blood transfusion for 2 – 4
weeks to raise the number of your red blood cells. Some
patient need transfusion only at certain time. For extra
protection pediatric patient need to get a full 3 doses of
hepatitis B vaccines before the blood transfusion.
•Chelation therapy: After many transfusion lot of iron can buildup in
the body. Beta thalassemia also makes body absorbs extra iron from
the food. All the extra iron can damage the body organs like heart,
liver etc. Chelation therapy is a treatment that remove the extra iron
from the body.
•Desferrioxamine: This medication is not recommended for use in
children less than 3 years old.
This medication is administered via IM, IV or SC.
IM: A dose of 1000 mg should be administered initially. This may be
followed by 500 mg every 4 hours for two doses.
SC: A daily dose of 1000-2000 mg/day should be administered over
8-24
IV : This may be followed by 500 mg over 4 hours for two doses.
Depending upon the clinical response, subsequent doses of 500 mg
may be administered over 4-12 hours. The total amount administered
should not exceed 6000 mg in 24 hours.
• Deferasirox- Exjade: Exjade (deferasirox) is an orally active
chelator that is selective for iron (as Fe3+). It is a tridentate
ligand that binds iron with high affinity in a 2:1 ratio.
Although deferasirox has very low affinity for zinc and
copper there are variable decreases in the serum
concentration of these trace metals after the administration
of deferasirox
DOSE: 20mg/kg orally TD and should not exceed above
30mg/kg TD.
• Do not chew tablet; disperse table in water, apple juice, or
orange juice
• Take on empty stomach at least 30 minutes prior to food
 SURGICAL TREATMENT:

• Splenectomy- decrease 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.
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