Vol 3 | Issue 2 | 2013 | 71-79.

ISSN 2249 - 7641

Print ISSN 2249 - 765X

International Journal of Pharmacology Research

www.ijprjournal.org

-THALASSEMIA-MINI REVIEW
P Sandhya Rani1*, S Vijayakumar1, G Vijay Kumar2, N Chandana1
1
Department of Pharmacy Practice, Vaagdevi College of Pharmacy, MGM Hospital, Warangal, Andhra Pradesh, India.
2
Department of Paediatrics, Kakatiya Medical College/MGM Hospital, Warangal, Andhra Pradesh, India.

ABSTRACT
-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the chains
of haemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The
incidence of symptomatic individual is estimated at 1 in 1,00,000 throughout the world annually. Whereas average incidence
of -thalassemia trait in India is 3.3% with 12 per 1,000 couples being at risk of having an affected offspring each year.
Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with
thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC)
transfusions. The purpose of this article is to elucidate the diagnosis and management of the -thalassemia patients. The
article briefly describing the epidemiology, types, clinical features, diagnosis, management of the -thalassemia. We describe
use of hematopoietic stem cell transplantation, which has produced cure rates as high as 97%, and the use of cord blood
transplantation. Finally, we touch on prevention and newer therapy that might be effective in the near future.

Keywords: -thalassemias, Anemia, Blood transplantation.

INTRODUCTION individuals. Phenotypically there are two forms of -

The term thalassemia is derived from the Greek
words Thalassa(sea) and Haema (blood) and refers to
disorders associated with defective synthesis of or -
globin subunits of haemoglobin (Hb)A(2;2), inherited as
pathologic alleles of one or more of the globin genes
located on chromosomes 11 () and 16 ( ). More than 200
deletions or point mutations that impair transcription,
processing or translation of or -globin mRNA have been
identified. The clinical manifestations are diverse, ranging
from absence of symptoms to profound fatal anemias in
utero or if untreated, in early childhood [1].
The thalassemia syndrome is classified according
to which of the globin chains, or , is affected. These 2
major groups, and -thalassemia, are sub classified
according to absent (o and o) or reduced (+ or +) globin
chain synthesis [1,2].
-thalassemias are a group of hereditary blood
disorders characterized by anomalies in the synthesis of the
chains of haemoglobin resulting in variable phenotypes
ranging from severe anemia to clinically asymptomatic
thalassemia: 0 - no globin chain synthesis, and + - with
some globin chain synthesis. Clinically, thalassemia
presents as beta-thalassemia minor (+ or 0), intermedia
(+/+; +/0) or major (0/0). Thalassemia Major, variably
referred to as "Cooley's Anemia" and "Mediterranean
Anemia", Thalassemia Intermedia and Thalassemia Minor
also called "beta-thalassemia carrier", "beta-thalassemia
trait" or "heterozygous beta-thalassemia". Apart from the
rare dominant forms, subjects with thalassemia major are
homozygotes or compound heterozygotes for beta0 or beta+
genes, subjects with thalassemia intermedia are mostly
homozygotes or compound heterozygotes and subjects with
thalassemia minor are mostly heterozygotes [3,4].
Epidemiology
-thalassemia is prevalent in Mediterranean
countries, the Middle East, Central Asia, India, Southern
China, and the Far East as well as countries along the north
coast of Africa and in South America. The highest carrier

Corresponding Author:- P. Sandhya Rani EMail ID: sandhya.pitta16@gmail.com

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frequency is reported in Cyprus (14%), Sardinia (10.3%),
and Southeast Asia. The incidence of symptomatic
individual is estimated at 1 in 1,00,000 through the world
annually. Whereas average incidence of -thalassemia trait
in India is 3.3% with 12 per 1,000 couples being at risk of
having an affected offspring each year. The incidence of -
thalassemia in different regions of India varies from 3% to
17%, with a mean prevalence of 4% [5]. It is estimated that
there are about 45 million carriers of the -thalassemia gene
in India, while about 15,000 affected infants are born every
year, contributing to about 10% of the total thalassemics
born all over the world [6,12].
TYPES OF BETA THALASSEMIA
a) Heterozygous +thalassemia or thalassemia minor
The heterozygous states for thalassemia are
associated with a mild but significant degree of anaemia.
The haemoglobin values for males ranged from 9 to 15 g/dl
with a mean value of 1213 g/dl. In females, the range has
been between 8 and 13 g/dl with mean value of 910 g/dl.
The red cell indices are quite characteristic, with reduced
MCH values in the 2022 picogram (pg) range and reduced
MCV values in the 60-70 flankolitre (fl) range [1]. It is
most unusual to find a -thalassemia carrier with an MCH
above 25pg or an MCV of more than 70 fl. The screening
for -thalassemia using an electronic cell counter is also
effective these days in India [2]. The main diagnostic
feature of this condition is an elevated HbA2 level in the
3.57.5% range. The condition is also called -thalassemia
trait. Some cases also show a slight elevation of HbF [6].
b) Homozygous 0thalassemia or thalassemia major
This is a serious condition where patients body
can't produce enough healthy haemoglobin or red blood
cells. Symptoms start to develop between the age of three
and six months. These include paleness, shortness of breath
and jaundice (where the whites of your eyes and your skin
become yellow). This condition usually presents with
severe anaemia within the first year of life [3]. Before the
first transfusion, these patients show a variable degree of
anaemia with marked variation in shape and size of their
red cells with hypochromia and a mild reticulocytosis. The
bone marrow shows erythroid hyperplasia and many of the
normoblasts contain ragged inclusions after incubation of
the marrow with methyl violet. The haemoglobin pattern in
this condition consists almost entirely of HbF with variable
HbA2 levels which may be reduced, normal or elevated [8].
Haemoglobin A is completely absent. Both parents show
the features of heterozygous -thalassemia with elevated
HbA2 levels [2].
c) Thalassaemia (delta) intermedia
This thalassemia results from complete absence of
both - and delta-chain synthesis, in most cases due to
extensive deletion of DNA in the -globin gene complex.
The high level of gamma chain production leads to
a relatively mild degree of globin chain imbalance and
hence these conditions are much milder than the
thalassaemia [1]. Homozygous condition is rare, but
heterozygous form is common and resembles clinically as
well as haematologically with -thalassemia trait. HbA2
level is normal or reduced and HbF is elevated from 5 to
20%. The Hb lepore disorders are forms of delta
thalassemia. These conditions result from the production of
delta fusion genes which direct the synthesis of delta
fusion chains. They arise by unequal crossing over between
the delta and globin genes, depending upon the position
and structure of abnormal crossing over [6,11]. The
symptoms of thalassemia intermedia vary from one
person to another. They are similar to those of
thalassemia major but less severe. Some people may have
mild anaemia and grow normally while others may need
regular blood transfusions to help them grow.
Aetiology
Thalassemia is directly linked to genetics and how
the genes that affect haemoglobin production are inherited.
People with moderate to severe forms received variant
genes from both parents. People who are carriers of the
disease received variant genes from one parent and normal
genes from the other parent [3].
This disorder is caused from a mutation or deletion
of the globin production genes which leads to decreased
production [9]. As a result, the globin protein chains make
an abnormal haemoglobin amount which decreases the
synthesis of haemoglobin. The quantity of the disruptions
in the chain synthesis determines the severity of the
Thalassemia [1,4].
Pathophysiology
The reduced amount (beta+) or absence (beta0) of
beta globin chains result in a relative excess of unbound
alpha globin chains that precipitate in erythroid precursors
in the bone marrow, leading to their premature death and
hence to ineffective erythropoiesis [9]. The degree of globin
chain reduction is determined by the nature of the mutation
at the beta globin gene located on chromosome [11].
Peripheral haemolysis contributing to anemia is
less prominent in thalassemia major than in thalassemia
intermedia, and occurs when insoluble alpha globin chains
induce membrane damage to the peripheral erythrocytes
[10]. Anemia stimulates the production of erythropoietin
with consequent intensive but ineffective expansion of the
bone marrow (up 25 to 30 times normal), which in turn
causes the typical previously described bone deformities.
Prolonged and severe anemia and increased erythropoietic
drive also result in hepatospleenomegaly and
extramedullary erythropoiesis [3,10][Fig.1].
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survival, which leads to so many complications. These

Fig.1. Pathophysiology of -thalassemia
Hereditary transmission
The beta-thalassemias are inherited in an
autosomal recessive manner. The parents of an affected
child are obligate heterozygotes and carry a single copy of a
disease-causing beta globin gene mutation. At conception,
each child of heterozygotes parents has 25% chance of
being affected, 50% chance of being an asymptomatic
carrier, and 25% chance of being unaffected and not carrier.
The parents of the pro-band have a 1 in 4 (25%) risk of
having further affected children in each pregnancy.
Dominant forms of beta-thalassemia, associated
with mutations that result in the production of highly
unstable beta globulin variants and leading to a clinically
manifesting phenotype of beta-thalassemia.
relate to inadequate transfusions, transfusion-related
infections, allow sensitization, iron-overload related
cardiac, endocrine and liver disturbances and toxicities of
iron chelators [22]. Many of these problems are strongly
age dependent. Heart disease is the most important
complication and the main determinant of survival [16]. It
is responsible for more than half of the deaths. It may take
the form of cardiomyopathy, pulmonary hypertension, heart
failure, arrhythmias, pericarditis and myocarditis [21,24].
Although iron over-load is the main cause but other factors;
genetic, immune or infective, may also be important.
Endocrine complications include diabetes mellitus,
hypothyroidism, hypoparathyroidism, hypogonadism and
delayed puberty [14,20]. Endocrine complications along
with osteoporosis, trace elements deficiency and other
metabolic disturbances also lead to growth failure and short
stature [17,15,18]. Less significant complications include
hepatic involvement, neurological complications, and
psychological manifestation [19,7].
Frequent blood transfusion can also lead to
increased chances of transfusion related infections.
Common blood reactions associated with transfusions are
non-hemolytic reactions, allergic reactions, acute hemolytic
reactions, autoimmune hemolytic anemia, delayed
transfusion reactions, transfusion related acute lung injury
(TRALI) and graft vs. host disease (GVHD), transfusion
transmitted infections are hepatitis B, C, HIV, malaria and
syphilis [23][Fig.2].

Clinical features of thalassemic syndromes

Fatigue
Weakness
Shortness of breath
Pale appearance
Irritability
Facial bone deformities
Yellow discoloration of the skin (jaundice)
Slow growth
Protruding abdomen
Dark urine

Complications of -thalassemia
-thalassemia major patients may need to have Fig 2. Complication of beta thalassemia
repeated blood transfusions throughout their life for

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DIAGNOSIS
Clinical Diagnosis
Thalassemia major is usually suspected in an
infant younger than two years of age with severe microcytic
anemia, mild jaundice and hepatospleenomegaly.
Thalassemia intermedia presents at a later age with similar
but milder clinical findings [26]. Carriers are usually
asymptomatic, but sometimes may have mild anemia.
Haematologic Diagnosis
RBC indices show microcytic anemia.
Thalassemia major is characterized by reduced Hb level (<7
g/dl), mean corpuscular volume (MCV) > 50 < 70 fl and
mean corpuscular Hb (MCH) > 12< 20 pg. Thalassemia
intermedia is characterized by Hb level between 7 and 10
g/dl, MCV between 50 and 80 fl and MCH between 16 and
24pg. Thalassemia minor is characterized by reduced MCV
and MCH, with increased HbA2 level [3].
Peripheral blood smear
Affected individuals show RBC morphologic
changes [microcytosis, hypochromia, anisocytosis,
poikilocytosis (spiculated tear-drop and elongatedcells),
and nucleated RBC (i.e., erythroblasts)]. The number of
erythroblasts is related to the degree of anemia and is
markedly increased after spleenectomy. Carriers have less
severe RBC morphologic changes than affected individuals.
Erythroblasts are normally not seen [25].
Qualitative and quantitative Hb analysis
By cellulose acetate electrophoresis and DE-52
microchromatography or HPLC identifies the amount and
type of Hb present. The Hb pattern in beta-thalassemia
varies according to beta-thalassemia type. In beta0
thalassemia, homozygotes HbA is absent and HbF
constitutes the 92-95% of the total Hb. In beta+ thalassemia
homozygotes and beta+/beta0 genetic compounds HbA
levels are between 10 and30% and HbF between 70-90%.
HbA2 is variable in beta thalassemia homozygotes and it is
enhanced in beta thalassemia minor.
Hb electrophoresis and HPLC also detect other
haemoglobinopathies (S, C, E, Lepore) that may interact
with beta-thalassemia.
Molecular Genetic Analysis
The prevalence of a limited number of mutations
in each population has greatly facilitated molecular genetic
testing. Commonly occurring mutations of the beta globin
gene are detected by PCR-based procedures. The most
commonly used methods are reverse dot blot analysis or
primer-specific amplification, with a set of probes or
primers complementary to the most common mutations in
the population from which the affected individual
originated. If targeted mutation analysis fails to detect the
mutation, beta globin gene sequence analysis can be used to
detect mutations in the beta globin gene [27].
MANAGEMENT OF THALASSEMIA
Transfusion therapy
The goals of transfusion therapy are correction of
anemia, suppression of erythropoiesis and inhibition of
gastrointestinal iron absorption, which occurs in non
transfused patients as a consequence of increased, although
ineffective, erythropoiesis.
The decision to initiate a regular transfusion
program in a child newly diagnosed with thalassemia must
take into account both laboratory and clinical findings. An
overlap of genotype and phenotype expression make the
clinical assessment the most important step in
distinguishing TM from TI. If the child is growing poorly
and has developed facial or other bone abnormalities,
and/or when Hb levels are 7 g/dL, regular transfusions
will be beneficial.
Before the first transfusion, patients RBCs are
typed for Rh and ABO antigens. At the same time,
cytomegalovirus status should be obtained.
Cytomegalovirus-negative blood products are
recommended for potential candidates for curative stem cell
transplantation (SCT). Parents and first-degree relatives
should not be blood donors for these candidates. Hepatitis
B vaccination is given before transfusion therapy, as is
hepatitis A vaccine when age appropriate [28].
Several different transfusional regimens have been
proposed over the years, but the most widely accepted aims
at a pretransfusional Hb level of 9 to 10 g/dl and a post-
transfusion level of 13 to 14 g/dl. This prevents growth
impairment, organ damage and bone deformities, allowing
normal activity and quality of life. The frequency of
transfusion is usually every two to four weeks. Shorter
intervals might further reduce the overall blood
requirement, but are incompatible with an acceptable
quality of life. The amount of blood to be transfused
depends on several factors including weight of the patient,
target increase in Hb level and hematocrit of blood unit. In
general, the amount of transfused RBC should not exceed
15 to 20ml/kg/day, infused at a maximum rate of 5
ml/kg/hour, to avoid a fast increase in blood volume. To
monitor the effectiveness of transfusion therapy, some
indices should be recorded at each transfusion, such as pre-
and post-transfusion Hb, amount and hematocrit of the
blood unit, daily Hb fall and transfusional interval.
A clinical record of all transfusion events should
be monitored annually to identify hyperspleenism. A record
of weight, the amount of blood transfused at each visit, and
the pretransfusion Hb level is needed to calculate the annual
transfusion requirement. Although red cell transfusions are
life savers for patients with thalassemia, they are
responsible for a series of complications and expose the
patients to a variety of risks. Iron overload is the most
relevant complication associated with transfusion therapy
[29].
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Iron overload assessment and treatment
As a consequence of repeated long-life red blood
cell transfusions, essential for survival, patients with
thalassemia major accumulate over time iron in the body.
Excess iron is toxic to many tissues, including the liver,
endocrine organs and heart, leading to a series of
complications which cause morbidity and mortality in these
patients. Hypogonadism (35-55% of the patients),
hypothyroidism (9-11%), hypoparathyroidism (4%),
diabetes (6-10%), liver fibrosis, and heart dysfunction
(33%) [14, 20]. Iron status should be accurately assessed in
order to evaluate its clinical relevance, the need for
treatment, and the timing and monitoring of chelation
therapy [30].
There is variability in iron deposition between and
within different organs. Serum ferritin is the most
commonly used indirect estimate of body iron stores, but
this reflects only 1% of the total iron storage pool. In
addition, interpretation of ferritin values may be
complicated by a variety of conditions. Reliance on serum
ferritin alone can lead to an inaccurate assessment of body
iron stores in individual patients. The hepatic iron
concentration by liver biopsy is considered the most
accurate and sensitive method for determining the body
iron burden. However, this is an invasive technique with a
low but recognized complication rate; the result is affected
by hepatic fibrosis (especially in small biopsies),which is
common in thalassemia as a result of increased liver iron
and HCV infection, and iron has been shown to be
unevenly distributed in the thalassemic liver even in the
non-cirrhotic stages. Endomyocardial biopsy can evaluate
iron deposition in the heart in thalassemia, but is not a
routine part of patient management due to the invasiveness
of the technique and the heterogeneous deposition of iron in
the heart [31, 32]. In addition, iron has been reported to be
absent from the right ventricular sub endocardium in some
patients with cardiac iron overload.
There are non-invasive techniques that can assess
tissue iron. Both magnetic resonance (MR) and magnetic
susceptometry are significantly affected by iron, and both
show changes in iron overload. However, to date only MR
can be applied to a moving organ such as the heart.
Fortunately there has been substantial progressing the speed
and image quality of cardiovascular MR in recent years,
and therefore we investigated its use in assessing
myocardial iron in thalassemia. Iron shortens T2*
relaxation time, which has become the most sensitive,
robust and therefore most used measure of cardiac iron. In
2001 Anderson et al.61 published a fundamental paper
describing the relationship between cardiac T2* and left
ventricular ejection fraction in patients with thalassemia
major. Cardiac T2* greater than 20 milliseconds (ms)
indicates normal iron content, while values between 10 and
20 ms or lower than 10 ms indicate moderate or severe iron
overload respectively. As T2* decreases below 20 ms,
increases the risk of having a decline in ejection fraction,
but it should be pointed out that many patients with
moderate or even severe cardiac iron may have normal
cardiac function, suggesting that T2* is able to identify
preclinical cardiac dysfunction [33,30].
Iron Chelators
As the body has no effective means for removing
iron, the only way to remove excess iron is to use iron
binders (chelators), which allow iron excretion through the
urine and/or stool. As a general rule, patients should start
iron chelation treatment once they have had 10-20
transfusions or when ferritin levels rise above 1000 ng/ml.
Important properties for an ideal iron chelator
High and specific affinity for Fe3+
High chelating efficiency
Slow rate of metabolism
Tissue and cell penetration
No iron redistribution
Relatively non-toxic
Achievement of negative iron balance
Low cost
Oral availability [9]
Deferoxamine
The first drug available for treatment of iron
overload was deferoxamine (DFO). Deferoxamineis not
orally absorbed and thus needs parenteral administration,
usually as a subcutaneous 8 to12 hour nightly infusion, 5-7
nights a week. Average dosage is 20-40 mg/kg body weight
for children and 30-50 mg/kg body weight for adults. In
high risk cases, continuous administration of DFO via an
implanted delivery system or subcutaneously, at doses
between 50 and 60 mg/kg per day, were the only options to
intensify the chelation treatment before the advent of the
combined therapy with DFO and deferiprone [34].
Implanted delivery systems are associated with risk of
thrombosis and infection. With DFO, iron is excreted both
in faeces (about 40%) and in urine. The most frequent
adverse effects of DFO are local reactions at the site of
infusion, such as pain, swelling, in duration, erythema,
burning, pruritus, wheals and rash, occasionally
accompanied by fever, chills and malaise. Other
complications, mainly associated with high doses of DFO
in young patients and low ferritin values are:
Sensorineural hypoacusia, particularly at high
frequencies
Ocular toxicity (night-blindness, blurred vision,
decreased visual acuity, impairment of colour vision,
cataract and other disturbances of the eye)
Retarded growth and skeletal changes with a
disproportionately short trunk and dysplasia of the long
bones
Infections by Yersinia Enterocolitica, and other
pathogens (Klebsiella Pneumoniae).
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The use of DFO decreases morbidity and mortality among reported following the post marketing use of DFX [30].
those who are able to comply with regular prolonged [Table 1]
infusions. However, because of the side effects and the
inconvenient parenteral administration, a consistent Table 1. Comparison of the 3 leading iron-chelating
proportion of patients is non-compliant, limiting the drugs in the management of thalassemia
Compound
usefulness of this chelator [36]. Deferoxamine Deferiprone Deferasirox

Molecular weight, Da 657 139 373

Deferiprone Recommended dose 30-60 mg/kg 75-100 mg/kg
20-40 mg/kg per
day
Deferiprone or L1 (DFP) is currently the only Subcutaneous or
Oral 3 times
orally active iron chelator available for clinical use. It was Delivery intravenous 8-12 h, 5-7
d/wk
daily
Oral once daily

licensed first in India in 1995 and subsequently in Europein Half-life 8-10 min 1.5-4 h 12-18 h
1999. At present, DFP is licensed in Europe for patients for Excretion 40%-60% faecal 90% urinary 90% faecal
whom treatment with DFO is inadequate. Gastrointestinal
Overall DFP is currently available in Gastrointestinal
upset, rash,
Ocular, auditory ocular, auditory
approximately 50 countries. Studies have demonstrated a Adverse effects
toxicity, growth
upset,
arthralgia,
toxicity,
retardation, local reversible
stable or declining mean serum ferritin and liver iron reactions, allergy
neutropenia,
increases in
Agranulocytosis
concentration during long-term therapy in most transfusion creatinine,
hepatitis
dependent patients, although iron accumulation continues
in others. Agranulocytosis is the most serious side effect, Combined chelation therapy
with a reported incidence of 0.6 per 100 patient years. More DFP and DFO can be given to the same patient
common but less serious side effects are gastrointestinal with different regimes: in combination on the same day,
symptoms (e.g., nausea, vomiting, gastric discomfort), either simultaneously (i.e. DFP given before breakfast,
arthralgia, zinc deficiency, and fluctuating ALT levels, lunch and dinner and DFO infused during the day) or
particularly in anti-hepatitis C virus (HCV)-positive sequentially (i.e. DFP as above and DFO infused
patients. Retrospective studies in patients treated with DFP overnight), or as alternate treatment (i.e. one or the other
have shown significant improvement in cardiac magnetic chelator is given on different days). Combination therapy is
resonance imaging (MRI), consistent with a reduction in considered an intensive chelation regimen and usually DFP
cardiac iron overload and improved cardiac function, in is administered every day, while subcutaneous DFO is
comparison with patients treated with DFO [8,9]. These given 2 to 7 days/week, according to the severity of iron
observations support a potential cardioprotective role of overload [34,35]. In patients with heart failure, to reinforce
DFP that needs to be confirmed in prospective randomized chelation, DFO can be given intravenously 24 h/day.
trials [30,3].
The potential advantages of the combined chelation are
Deferasirox Access to different iron pools
Deferasirox (DFX) is a once-daily, orally Prevention of non transferrin bound iron (NTBI)
administered iron chelator that a large program of clinical accumulation
trials has shown to be effective in adults and children. It Increased efficacy
received European Union marketing authorization as an
Decreased toxicity
orphan drug from the EMEA in 2002 and was authorized
Better compliance
for marketing in most countries in 2006. The recommended
starting dose of DFX for most patients is 20 mg/kg/day, Improved quality of life
although this can be modified to 10 or 30 mg/kg/day
depending on the number of transfusions a patient is Bone marrow transplantation (BMT)
receiving and whether the therapeutic goal is to decrease or Bone marrow transplantation (BMT) remains the
maintain body iron levels. The most frequent adverse only definitive cure currently available for patients with
events reported during treatment with DFX include thalassemia. The outcome of BMT is related to the
transient, mild-to-moderate gastrointestinal disturbances pretransplantation clinical conditions, specifically the
and skin rash. These events rarely require drug presence of hepatomegaly, extent of liver fibrosis, history
discontinuation and most resolve spontaneously. Mild, of regular chelation and hence severity of iron
usually nonprogressive increases in serum creatinine accumulation [37]. In patients without the above risk
(generally within the upper limit of normal) has been factors, stem cell transplantation from an human leukocyte
observed in approximately a third of patients. Creatinine antigen (HLA) identical sibling has a disease free survival
levels returned spontaneously to baseline in most of rate over 90%. The major limitation of allogenic BMT is
patients and data from up to 3.5 years of treatment in more the lack of an HLA-identical sibling donor for the majority
than1000 patients have confirmed that creatinine increase is of affected patients. In fact, approximately 25-30% of
non progressive. However, cases of renal failure have been thalassemic patients could have a matched sibling donor.

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BMT from unrelated donors has been carried out
on a limited number of individuals with beta-thalassemia.
Provided that selection of the donor is based on stringent
criteria of HLA compatibility and that individuals have
limited iron overload, results are comparable to those
obtained when the donor is a compatible sib. However,
because of the limited number of individuals enrolled,
further studies are needed to confirm these preliminary
findings. If BMT is successful, iron overload may be
reduced by repeated phlebotomy, thus eliminating the need
for iron chelation. Chronic graft versus-host disease
(GVHD) of variable severity may occur in 5-8% of
individuals [41, 38].
Cord blood transplantation
Cord blood transplantation from a related donor
offers a good probability of a successful cure and is
associated with a low risk of graft versus- host disease
(GVHD) [3]. For couples who have already had a child
with thalassemia and who under take prenatal diagnosis in a
subsequent pregnancy, prenatal identification of HLA
compatibility between the affected child and an unaffected
foetus allows collection of placental blood at delivery and
the option of cord blood transplantation to cure the affected
child. On the other hand, in cases with an affected fetus and
a previous normal child, the couple may decide to continue
the pregnancy and pursue BMT later, using the normal
child as the donor.
FUTURE THERAPIES
Stimulating HbF production
Individuals with Hereditary persistence foetal
haemoglobin (HPFH) demonstrate that preventing or
reversing the switch from foetal to adult haemoglobin
would provide efficacious therapy for thalassemia and
various other haemoglobinopathies. It has been observed
that some patients recovering from cytotoxic therapy have
reactivated HbF synthesis. Several therapeutic agents such
as erythropoietin, hydroxyurea, cytarabine and butyrate
analogs have produced an increase in HbF synthesis in the
thalassemic patients by stimulating the HbF-producing
progenitor cell population [1,4].
Gene therapy
Thalassemia can be cured by introducing or
correcting a gene into the hematopoietic compartment or a
single stem cell. Initial attempts at gene transfer have
REFERENCES
1. Eliezer AR and Patricia JG. How I treat thalassemia. Blood Journal Hematology library Org, 118, 2011, 3479-3488.
2. Amit KM, Archana Tiwari. - Thalassaemia - A Fatal Blood Disorder. Int. J. Rev. Life. Sci, 1(2), 2011, 83-87.
3. Renzo Galanello and Raffaella Origa. Beta-thalassemia. Galanello and Origa Orphanet Journal of Rare Diseases, 5, 2010,
11.
4. Alain J, Marengo-Rowe MD. The thalassemias and related disorders. Proc (Bayl Univ Med Cent), 20, 2007, 2731.
5. Sood SK, Madan N, Colah R, Sharma S, Apte SV. Collaborative Study on thalassaemia. Report of ICMR Task Force Study.
Indian Council of Medical Research, 1993, 20-27.
proved unsuccessful due to the limitation of available gene
transfer vectors. The newer approaches to overcome these
limitations, includes the introduction of lentiviral vectors.
New approaches have also focused on targeting the specific
mutation in the globin genes, correcting the DNA sequence
or manipulating the development in DNA translocation and
splicing to restore globin chain synthesis [41,40].
PREVENTION
Creating awareness
Creating awareness about thalassemia to the
general population, government and medical communities
by holding seminars, workshops and writing articles in the
daily newspapers, broadcasting in television and radio is of
prime importance.
Genetic counselling
Provides information for individuals and at risk
couples (i.e. both carriers) regarding the mode of
inheritance, the genetic risk of having affected children and
the natural history of the disease including the available
treatment and therapies under investigation [42].
Prenatal diagnosis
Acceptance of prenatal diagnosis and termination
of affected foetuses are dependent on the early
identification of couples at risk. Prenatal diagnosis for
pregnancies at increased risk is possible by analysis of
DNA extracted from foetal cells obtained by amniocentesis,
usually performed at approximately 15-18weeks' gestation
or chorionic villi sampling at 11 weeks' gestation. Both
disease-causing alleles must be identified before prenatal
testing can be performed. New technology using foetal
DNA obtained from maternal plasma or maternal peripheral
blood has also been developed but is not routinely available
[39].
CONCLUSION
Thalassaemia major imposes highly clinical,
psychological burden on the patients and economical
burden their family and hence our article briefly describing
the epidemiology, types, clinical features, diagnosis,
management of the -thalassemia. We describe use of
hematopoietic stem cell transplantation, which has
produced cure rates as high as 97%, and the use of cord
blood transplantation. Finally, we touch on prevention and
newer therapy that might be effective in the near future.
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43. Thalassaemia major imposes highly clinical, psychological burden on the patients and economical burden.

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