Thalassemia

Presentor:
Don Jayric Depalobos
Thalassemia
 refersto a group of genetic disorders of
globin chain production
 imbalance between the α-globin and β-
globin chain production
 characterized by a reduced or absent
one or more of the globin chains of adult
hemoglobin
2 Basic Groups of Thalassemia
 Alpha (α) Thalassemia
 In alpha-thalassemia, the alpha genes are
deleted; loss of one gene or both genes from
each chromosome 16 may occur, in association
with the production of some or no alpha globin
chains
 Beta (β) Thalassemia
 In beta-thalassemia, defective production
usually results from disabling point mutations
causing no or reduced beta chain production
Beta-Thalassemia
β-Thalassemia syndromes result from a decrease in β-
globin chains, which results in a relative excess of α-
globin chains.

a)β0-Thalassemia refers to the absence of production of

the β-globin. When patients are homozygous for the
β-thalassemia gene, they cannot make any normal β
chains (HbA).
b)β+-Thalassemia indicates a mutation that makes
decreased amounts of normal β-globin, but it is still
present (HbA).

β0-Thalassemia syndromes are more severe than β+-

thalassemia syndromes, but there is significant variability
between the genotype and phenotype.
Beta-Thalassemia
β-Thalassemia syndromes result from a decrease
in β-globin chains, which results in a relative
excess of α-globin chains.

a)β-Thalassemia major refers to the severe β-

thalassemia patient who requires early
transfusion therapy and often is homozygous
for β0 mutations.

b)β-Thalassemia intermedia is a clinical

diagnosis of a patient with a less-severe
clinical phenotype that usually does not
require transfusion therapy in childhood.
Alpha-Thalassemia
 Inα-thalassemia, there is an absence or
reduction in α-globin production.
 An α0-mutation indicates no α-chains
produced from that gene.
 An α+ mutation produces a decreased
amount of α-globin chain.
Epidemiology
 Although most are rare, the 20 most
common abnormal alleles constitute 80%
of the known thalassemias worldwide;
 3% of the world’s population carries alleles
for β-thalassemia
 Southeast Asia 5-10% of the population
carry alleles for α-thalassemia
 In the United States, an estimated 2,000
persons have β-thalassemia major.
 Pathophysiology
β-globin chains reduced

Excess unpaired α chains

Precipitated insoluble inclusions

Interfere with Damage Perturb the Reduced

RBC cell Cell internal ionic deformability
divisions Membrane environment

Intramedullary death of erythroid cells (ineffective erythropoiesis)

Bone changes Hepatosplenomegaly Persistent

Skull Changes Progressive
Mallar Prominence Anemia
Clinical Manifestations
 Beta-Thalassemia Minor
 Usually no sign or symptoms except for a mild persistent
anemia not responding to hemanitics

 Beta-Thalassemia Major
 Pallor – fatigue, irritability
 Growth retardation
 Recurrent infections
 Bony abnormalities specially of the facial
bones, hemolytic facies,
caput quadtratum
 Enlarged Spleen and Liver
 Delayed sexual development
Laboratory Findings
MCV Microcytosis

MCH Hypochromia

Hemoglobin Fall progressively to <6g/dL

Reticulocyte count <8%

Serum Ferritin Elevated

Transferrin Saturation Elevated

Hemoglobin Increase in HbA2

Electrophoresis production
Diangnostic Imaging
Management
 Transfusion Therapy
 Leukoreduced
 3-4week interval
 goal being to maintain a pretransfusion
hemoglobin level of 9.5-10.5 g/dL.

 Ongoing monitoring for transfusion-associated

transmitted infections (hepatitis A, hepatitis B,
hepatitis C, HIV), alloimmunization, annual blood
transfusion requirements, and transfusion reactions
is essential.
Management
 Iron Overload and Chelation therapy
 Iron Overload occurs in thalassemic
Patients due to:
 Treatment with multiple transfusions
 Ineffective erythropoeisis
 Excessive dietary absorption of iron from g
 Lack of physiologic excretory mechanism for
the excess iron
Management
 Iron Overload and Chelation therapy
 Initiation of Chelation therapy
 Serum ferritin >1000ng/dL
 Patient has received 15-20 transfusions
 Hepatic Iron Concentration of >2,500 ug/g dry
weight

Iron Chelators:
1. Deferoxamine
2. Deferasirox
3. Deferiprone
Management
 Hydroxyurea
 Increases stress erythropoeisis, which results
to increase HbF production.

 Hematopoeitic Stem Cell transplantation

 Successful in >3000 patients with
Thalassemia Major
 Success in children less than 15 yr old
Management
 Splenectomy
 May be required in patients who develops
hypersplenism.
Management
 Guidelines for Splenectomy
 Recommended for:
 Moderate – Severe Hypersplenism
 Frequent hupoplastic or aplastic crises
 Poor Growth
 Cardiomegaly

 Criteria: >6 years old

Management
 Guidelines for Splenectomy
 Pre-splenectomy Vaccinations:
 Pneumococcus
 Menigococcus
 H. influenzae type B