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OVERVIEW ON THALASSEMIAS: A REVIEW ARTICLE

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“Overview on Thalassemias: A review article”

ISSN No. 2394-3971

Review Article
OVERVIEW ON THALASSEMIAS: A REVIEW ARTICLE
Dharmesh Chandra Sharma1*, Anita Arya2, Purnima Kishor3, Poonam Woike4, Jyoti Bindal5
1. Associate Blood Transfusion Officer (ABTO), Incharge Component & Aphaeresis Unit, Blood
Bank, G. R. Medical College, Gwalior. India.
2. Medical Officer, Blood Bank, G. R. Medical College, Gwalior.
3. Department of Biochemistry, Jiwaji University, Gwalior
4. Resident, Department of Pathology, G. R. Medical College, Gwalior.
5. Professor and HOD, Department of Obstetrics & Gynecology, G. R. Medical College, Gwalior.

Submitted on: June 2017

Accepted on: June 2017
For Correspondence
Email ID:

Abstract
Thalassemia’s are genetic disorders inherited from a person’s parents. Thalassemia’s are
prevalent worldwide with 25,000 deaths in 2013.Highest rates are in the Mediterranean, Italy,
Greece, Turkey, West Asia, North Africa, South Asian, and Southeast Asia. The β-thalassemia
major is the most severe form and the affected children are dependent on regular blood
transfusions for survival. One of the major complications in chronically transfused patients is
development of irregular antibodies and in this situation; further transfusion of compatible red
cell is difficult. Hemoglobinopathies imply abnormalities in the globin proteins themselves.
Health complications are mostly found in thalassemia major and intermediate patients. Signs
and symptoms include severe anemia, poor growth and skeletal abnormalities during infancy.
Untreated thalassemia major eventually leads to death, usually by heart failure. Diagnosis by
hematologic tests, hemoglobin electrophoresis, and DNA analysis. Individuals with severe
thalassemia require blood transfusion, drug therapy i.e. deferoxamine, deferasirox,
deferiprone, and bone marrow transplant. Bone Marrow Transplant (BMT) is still remains the
only definitive cure available for patients with Thalassemia. Gene therapy for β- Thalassemia
Medico Research Chronicles, 2017

is still on trial and a hope for future. Genetic studies (DNA analysis) to investigate deletions
and mutations in the alpha- and beta-globin-producing gene help in correct diagnosis and
improved management in thalassemic patients. This topic will review the clinical features of
thalassemia while focusing on pathophysiology, clinical features, complication, management,
screening and diagnosis.

Keywords - Thalassemia, Hemoglobinopathies, Bone Marrow Transplant, Gene

Therapy.
Introduction Mediterranean and anemia (“weak blood”).
The name thalassemia derived from a Another term found in literature, although
combination of two Greek words: Thalassa infrequently, is Cooley’s anemia after the
meaning the sea (Cooley et al., 1925, 1927; name of Prof. Cooley Thomas, a
Bradford and Dye, 1936) [1, 2, 3] that is the pediatrician in the USA who first described

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the clinical characteristics of this disorder responsible for its naming [19]. In Europe,
in patients of Italian origin 1925[1, 2]. the highest concentrations of the disease
Thalassemia is genetic blood disorders are found in Greece, coastal regions of
inherited from a person’s parents that can Turkey (particularly the Aegean Region
result in the abnormal formation such as Izmir, Balikesir, Aydin, Mugala,
of hemoglobin [4, 5]. There are two main and Mediterranean Regions such as
types, alpha and beta Thalassemia [4]. The Antalya, Adna, Mersin), in parts of Italy,
severity of alpha and beta thalassemia particularly southern Italy and the lower
depends on how many of four genes for Povalley. The major Mediterranean islands
alpha or two genes for beta globin are (except Balearics) such as Sicily, Sardinia,
missing [5]. Thalassemia’ are widespread Malta, Corsica, Cyprus, and Crete are
throughout the Mediterranean region, heavily affected in particular. Other
Africa, the Middle East, the Indian Mediterranean people, as well as those in
subcontinent and South-East Asia [6]. As the vicinity of the Mediterranean, also have
of 2013 thalassemia occurs in about 208 high rates of thalassemia, including the
million people with 4.7 million having people of West Asia and North Africa. Far
severe disease [7]. It resulted in 25,000 from the Mediterranean, South Asian are
deaths in 2013 down from 36,000 deaths in also affected with World’s highest
1990[8]. Males and females have similar concentrations of the carriers (30% of the
rates of disease [9]. Diagnosis is typically population) being in the Maldives [20, 21].
by blood tests including a complete blood Nowadays, it is found in populations living
count, special hemoglobin tests and genetic in Africa, the Americas, and Tharus people
tests [10]. The current management of β- in the Terai region of Nepal and India [22].
thalassemia major patient is based on It is believed to account for much lower
regular transfusion of packed red cells and malaria sickness and deaths [23],
effective chelating therapy [11-14]. The accounting for the historic ability of Tharus
aim of the transfusion therapy is to correct to survive in areas heavy malaria
anemia and to maintain sufficient infestation, where other could not.
circulating level of hemoglobin (Hb) to Thalassemia are particularly associated
suppress endogenous erythropoiesis [15]. with people of Mediterranean origin, Arabs
Major complication in chronically (especially Palestinian and people of
transfused patients is iron overload [16]. Palestinian descent), and Asians [24].
Thirty years have passed since the first Maldives has the highest incidence of
hemopoietic stem cell transplant (HSCT) in Thalassemia in the world with carrier rate
thalassemia and this procedure now stands of 18% of the population. The estimated
today as a widely applied treatment for the prevalence is 16% in people from
definitive cure of thalassemia major, with Cyprus, 1% in Thailand, and 5-10% in Iran,
Medico Research Chronicles, 2017

more than 3000 HSCTs performed and 3-8% from Bangladesh, China, India,
worldwide [17]. Even at a time when we Malaysia, and Pakistan [25,26,27,28].
are finally entering the long-awaited gene Thalassemia also occur in descendants of
therapy era, to this day HSCT remains the people from Latin America, Mediterranean
only available curative option for countries (e.g. Greece, Italy, Spain, and
thalassemia major [18] but It is not possible others), and Portugal [25]. A bio-
to manage and afford HSCT in each and geographic analysis with the aid of tools;
every thalassemic patient in Indian such as Geographic Information System
subcontinent. (GIS) may provide an insight into the non-
Prevalence biological factors influencing different loci
The beta form of thalassemia is particularly in the β -globin gene in different
prevalent among Mediterranean people, geographical regions [29]
and this geographical association is

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Pathophysiology The β globin chains are encoded by a single

Normal adult hemoglobin is expressed as gene on chromosome 11; α globin chains
A2, A and F (fetal). Ninety-five to ninety- are encoded by two closely linked genes on
eight percent of adult hemoglobin is A, the chromosome 16 [31]. Thalassemia occurs
major hemoglobin, which consists of two α when there is decreased or absent
- and two β -chains (α2 β2). Hemoglobin A2 production of one of the types of globin
(α2, δ2), the remainder of hemoglobin in chains (most commonly either α or β), that
adults is a minor component (less than cause insufficient amount of normal
3.3%), and structure of globin chains. This results in an
1% or less of F (α2, γ2) [30], the gamma imbalance between α - and β -chains and
hemoglobin (Hb-F) is the predominant causes the clinical features of Thalassemia
hemoglobin found only during fetal [32]; it can be separated into two major
development. The equal production of α types such as α -thalassemia and β -
and non- α (β, δ, γ) globin chains is thalassemia. Thalassemia Syndromes,
necessary for normal red blood cell (RBC) Genotypes, and clinical features are
function. summarized in table no. 1

Table No. 1 Thalassemia Genotypes, Syndromes and clinical features

α Thalassemia α Gene Globins Chain Hemoglobin Clinical features

Normal αα / αα α2 β2 A Normal
Silent carriers αα / α - α2 β2 A Asymptomatic
Trait (minor) α-/α- α2 β2 A Asymptomatic
- - / αα
Hb H disease --/-α α2 β2, β4 A, H Jaundice,
splenomegaly,
occasionally need
transfusion;
Hydrops --/-- γ4, ξ2γ2 Barts, Lethal, Death in
Fetalis Portland utero or shortly after
birth
β Thalassemia β Gene Globins Chain Hemoglobin Clinical features
Normal β/ β α 2 β2 A Normal
Thalassemia β+ / β α 2 β2, α 2 δ 2, α 2 γ2 A, A2, F Asymptomatic
minor (Trait) β0 / β
Thalassemia β+/ β0 α 2 β2, α 2 δ 2, α 2 γ 2 A, F clinical phenotype
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Intermediate β+ / β+ between
thalassemia trait &
thalassemia major
Thalassemia β+ / β+ α 2 β2, α 2 δ 2, α 2 γ 2 A, A2, F Require chronic
Major β0/ β0 α 2 δ 2, α 2 γ 2 F, A2 transfusion;
iron overload in
endocrine
abnormalities and
chronic organ
damage
HPFH γ/ γ α2γ2 F Mild

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The most common combination of β- destruction of red cell precursors (i.e.

thalassemia with abnormal Hb or structural ineffective erythropoiesis). Those red cells
Hb variant with thalassemic properties is that mature and enter the circulation
Hb-E/β-thalassemia which is most contain α chain inclusion, which interfere
prevalent in an area stretching from with their passage through the
northern India and Bangladesh, through microcirculation, particularly in the spleen.
Laos, Cambodia, Thailand, Vietnam, These cells, which show a variety of
Malaysia, the Philippines, and Indonesia abnormalities of membrane structure and
[33]. These Hb-E/beta-Thalassemia may permeability, are prematurely destroyed
have mild to severe symptoms. In our and thus the anemia of β thalassemia results
previous study, we found that Hb-E/β- from both ineffective erythropoiesis and a
Thalassemia is the second most common shortened cell survival. The anemia acts as
cause of transfusion-dependent a stimulus to erythropoietin production and
thalassemia in the Gwalior and Chambal this causes expansion of the bone marrow,
region of central India [34]. which may lead to serious deformities of
The Pathophysiology of alpha thalassemia the skull and long bones. Because the
is different to that of beta Thalassemia. A spleen is being constantly bombarded with
deficiency of α chain leads to the abnormal red cells, it hypertrophies [36].
production of excess chains or β chains, Clinical Manifestations
which form Hb Bart's and Hb H Three main forms have been described
respectively. These soluble tetramers do thalassemia major, thalassemia
not precipitate in the bone marrow and intermediate and thalassemia minor. Alpha
hence erythropoiesis is more effective than thalassemia silent carriers generally have
in β Thalassemia [35]. Unlike the deletion no signs or symptoms of the disorder.
that constitute most of the alpha People who have alpha or beta thalassemia
thalassemia syndromes, beta thalassemia is trait can have mild anemia. However, many
caused by mutation on chromosome 11 that people with this type of thalassemia may be
affect all aspect of beta globin production: asymptomatic or experience very few
transcription, translation, and the stability symptoms. Symptoms may be worse in
of the beta globin production [36]. individuals that are pregnant, under stress,
Monitoring of the dose of iron chelator, or malnourished. Symptoms may include:
according to the type of mutation in the Fatigue. This may be the only symptom
beta globin gene, may help to improve the that an individual with beta thalassemia
compliance of beta thalassemic to chelation minor exhibits [39] (Satwani et al., 2005).
therapy and prevent side-effects in patients People with beta thalassemia intermedia
with beta plus mutations [37]. Alpha have mild to moderate anemia. In the beta
hemoglobin stabilizing protein has a causal thalassemia intermedia, the patients with
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relationship with the severity of beta Hb of much below 7 or 8 gm/dl excess

Thalassemia [38]. energy consumption due to the profound
The molecular defects in β thalassemia hemolysis can produce small stature, poor
result in absent or reduced β chain weight gain, poor energy levels,
production. Alpha chain synthesis is susceptibility to infection and yellow
unaffected and hence there is imbalanced discoloration (jaundice) of the skin, eyes,
globin chain production leading to an and mucous membranes caused by
excess of α chains. In the absence of their increased amount of bilirubin in the blood.
partners, they are unstable and precipitate Beta Thalassemia major (also called
in the red cell precursors, giving rise to Cooley's anemia) has severe form of
large intracellular inclusions, which Thalassemia and symptoms appears in first
interfere with red cell maturation. Hence, two years of life. Affected infants fail to
there is a variable degree of intramedullary thrive and gain weight normally and

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become progressively pale. Feeding Heart Diseases, such as congestive heart

problems, diarrhea, irritability, fever and failure and abnormal heart rhythms, may be
progressive enlargement of the abdomen associated with severe Thalassemia [47].
due to splenomegaly and prominence of the Diagnosis
cheek bones tends to obscure the base of Several laboratory tests may be used to
the nose and to expose the upper teeth, help detect and diagnose Thalassemia like:
puffiness of the eyelid and a tendency to a Complete blood count (CBC), Blood
Mongoloid slant of the eyes are common smear, Iron studies, Hemoglobinopathy
presenting symptoms [40]. People with (Hb) DNA analysis (Genetic testing) [48],
hemoglobin H disease have severe and prenatal testing (Genetic testing
thalassemia. Signs and symptoms occur of amniotic fluid) [49]. The step in the
within the first 2 years of life. They may diagnosis of the different forms of
include severe anemia and other serious thalassemia include the initial recognition
health problems, such as: Pale and listless of the disease as thalassemic disorder and
appearance, Poor appetite, Dark urine. The its differentiation from other congenital
Hydrops Fetalis Syndrome is recognized and acquired disorder of hemoglobin
by the finding of a hydropic infant with a synthesis which can mimic the thalassemia
severe anemia, a thalassemic blood picture, syndromes [39]. In silent carrier state
and the presence of 80% or more Hb Barts Thalassemic Patients are essentially
on hemoglobin electrophoresis [41]. asymptomatic and the CBC, hemoglobin
Complication of β-thalassemia includes electrophoresis, and peripheral smear are
iron over load, infections, bone marrow usually normal. Slight hypochromia and
deformities, enlarged spleen, and slow microcytosis may be evident by
growth rate and heart problems. People microscopic evaluation. In alpha
with β-thalassemia can get an overload of thalassemia minor the red cell is abnormal
iron in their bodies, either from the disease with microcytosis, hypochromia, and
itself or from frequent blood transfusions. elevated amount of Hb Bart noted (3%-8%)
Too much iron can result in damage to the [39].
heart, liver, and endocrine system, which The Hydrops Fetalis syndrome is
includes glands that produce hormones that recognized by the finding of a hydropic
regulate processes throughout the body infant with a severe anemia, a thalassemic
[42]. People with thalassemia have an blood picture, and the presence of 80% or
increased risk of infection. This is more Hb Barts on hemoglobin
especially true if the spleen has been electrophoresis [40]. The homozygous for
removed [43]. Thalassemia can make the the severe form of beta thalassemia are
bone marrow expand, which causes bones easily recognized by the hematological
to widen. This can result in abnormal bone change with very high level of Hb F; Hb A2
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structure, especially in the face and skull. values. The heterozygous states are
Bone marrow expansion also makes bones recognized by microcytic hypochromic red
thin and brittle, increasing the risk of cells and elevated level of Hb A2 [41].
broken bones [44]. The spleen aids in DNA analysis tests are used to help
fighting infection and filters unwanted confirm mutations in the alpha and beta
material, such as old or damaged blood globin-producing genes. DNA testing is
cells. Splenomegaly can make anemia not routinely done but can be used to help
worse, and it can reduce the life of diagnose thalassemia and to
transfused red blood cells. Severe determine carrier status, if indicated. More
enlargement of the spleen may necessitate than 250 mutations have been associated
its removal [45]. Anemia can cause a with beta thalassemia, though some cause
child's growth to slow. Puberty also may be no signs or symptoms. However, others
delayed in children with Thalassemia [46]. decrease the amount of beta globin

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production and some prevent it completely. hypersplenism may cause worsening

The presence of one of those mutations anemia, retarded growth and mechanical
confirms a diagnosis of beta thalassemia. disturbance from the large spleen,
The primary molecular test available for splenectomy is a relevant aspect of the
alpha thalassemia detects common management of thalassemia intermedia
mutations (e.g., deletions) in the two alpha [55-57].
genes HBA1 and HBA2. Each person has Presently, till today the Bone Marrow
two copies of each of these genes, Transplant (BMT) is still remains the only
called alleles, in their cells, one from their definitive cure available for patients with
mother and one from their father. These Thalassemia. Gene therapy for β-
alleles govern alpha globin production and Thalassemia is still on trial and a hope for
if mutations lead to functional loss of one future [58, 59]. First successful BMT was
or more of alpha genes, alpha thalassemia done in 1980s by Prof. Guido Lucarelli. In
occurs. Genetic testing of amniotic fluid is low –risk young patients, the thalassemia-
issued in the rare instances a fetus is at free survival is 87%, the mortality is 3 %.
increased risk for thalassemia. This is The drawback is that this curative method
especially important if both parents likely required an HLA (Human leukocyte
carry a mutation because that increases the Antigen)-matched compatible donor [60].
risk that their child may inherit a If the patient does not have an HLA-
combination of abnormal genes, causing a matched donor such as the first curative
more severe form of Thalassemia [50]. method requires, there is another curative
Treatment method called Bone Marrow
Most individuals with mild thalassemia Transplantation(BMT) from haploidentical
traits require no treatment. They may want mother to child (mismatched donor), in
to consider genetic counseling, however, which donor is the mother. It was invented
because they may pass the mutant gene on in 2002 by Doctor Pietro Sodani. The
to their children [51]. People with results are: thalassemia frees survival rate
hemoglobin H disease or beta thalassemia 70%, rejection 23 %, and mortality 7%.
intermedia will experience variable The best results are with very young
amounts of anemia throughout their life. patients [61]. BMT treatment for
They can live relatively normal lives but thalassemia is still not available for all
will require regular monitoring and may patients in Indian perspective, at our center
occasionally need blood transfusion. Folic out of 120 patients only one patient has
acid supplementation is often given, but gone for successful bone marrow transplant
iron supplementation is not recommended. [62].
[52]. Hb Bart hydrops Fetalis syndrome or The current management available for
alpha thalassemia major currently has no majority of β-thalassemia major patient in
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effective treatment and babies are usually low socio-economic countries like India is
miscarried, stillborn, or die shortly after regular transfusion of packed red cells;
birth. Attempts at intrauterine effective chelating therapy and
transfusions, after early prenatal detection management of complications of iron
with Doppler ultra-sonography of this overload [16]. The aim of the transfusion
condition, have been conducted, but most therapy is to correct anemia and to maintain
survivors experienced a high prevalence of circulating level of hemoglobin (Hb)
congenital malformations [53, 54] and sufficient to suppress endogenous
attempts should be discouraged until more erythropoiesis [15]. In transfusion
effective therapies (e.g., somatic gene dependent Thalassemia, the superiority of
therapy) are available [51]. regularly repeated transfusions, as
Treatment of individuals with thalassemia compared to transfusions only for
intermedia is symptomatic. As symptomatic anemia, was first recognized

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by Orsini in France and later by Wolman transfusions to avoid alloimmunization

and Piomelli in US, who suggested a against red cells. Prevalence of
transfusion program aimed at monitoring a Alloimmunization at our center was 3.3%
basal Hb level sufficient to eliminate [61]. Author(s) has also used other blood
hypoxia [63, 64]. Several different components like Neocytes concentrate/
regimens like hyper transfusion regimen ( pooled Neocytes and whole umbilical cord
the pre-transfusion Hb is maintained as >10 blood to the thalassemic patients in his
gm/dl with mean Hb of about 12 gm/dl, previous studies and results are fruitful
immediate post transfusion Hb rising to 14 [70,71].
gm/dl and returning to baseline after 3–4
weeks) , Super transfusion regimen (the Iron overload is the most relevant
pre-transfusion Hb is maintained at ≥11 complication associated with transfusion
gm/dl or a hematocrit of more than 35% therapy. When Patient is on a regular
with a mean Hb of about 14 gm/dl), while transfusion regimen progressively develop
in moderate transfusion regimen the pre- clinical manifestations of iron overload:
transfusion Hb is maintained at the values hypogonadism (35-55% of the patients),
between 9 and 10 gm/dl and to reach a post- hypothyroidism (9-11%),
transfusion level of 13 to 14 gm/dl have hypoparathyroidism (4%), diabetes (6-
been proposed over the years. This 10%), liver fibrosis, and heart dysfunction
prevents growth impairment, organ (33%) [40, 41]. A unit processed from 420
damage and bone deformities, allowing ml of donor blood contains approximately
normal activity and quality of life, and is 200 mg of iron, or 0.47 mg/ml of whole
associated with relatively low rates of donor blood. Normal intestinal iron
blood requirement and of iron absorption is about 1-2mg/day. In patients
accumulation [65]. The amount of blood to with thalassemia who do not receive any
be transfused depends on several factors transfusion, iron absorption increases
including the weight of the patient, and the several-fold. It has been estimated that iron
target increase in Hb level. Appropriate absorption exceeds iron loss when
graphs and formulae to calculate the expansion of red cell precursors in the bone
amount of blood to be transfused are marrow exceeds five times that of healthy
available [66, 67]. In general, the amount individuals [72]. Iron status should be
of transfused RBC should not exceed 15 to accurately assessed in order to evaluate its
20 ml/kg/day, infused at a maximum rate of clinical relevance, the need for treatment,
5 ml/kg/hour to avoid a fast increase in and the timing and monitoring of chelation
blood volume. therapy. The iron status of multi-transfused
Characteristics of blood products for patients can be assessed by several
transfusion: Careful selection of healthy methods. Serum ferritin has in general been
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voluntary donors is a prerequisite for found to correlate with body iron stores
obtaining safe blood units for patients with [73]. In recent years, nuclear magnetic
thalassemia. To avoid transfusion reactions resonance imaging (MRI) techniques for
from anti-leukocyte and anti-platelet assessing iron loading in the liver and heart
antibodies and transmission of viral agents have been introduced [74-75]. As the body
present in leukocytes such as has no effective means for removing iron,
cytomegalovirus, patients with thalassemia the only way to remove excess iron is to use
should receive leukoreduced packed red iron binders (chelator), which allow iron
cells [68, 69]. In the patients sensitized to excretion through the urine and/or stool. As
plasma proteins washed red cells may be a general rule, patients should start iron
beneficial. Extended red cell antigen typing chelation treatment once they have had 10-
including at least Rh antigens, Duffy, Kidd 20 transfusions or when ferritin levels rise
and Kell is recommended before starting above 1000 ng/ml [76].

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Mainly three chelation drugs available in treated, now it is a major focus of

the market are deferoxamine (DFO), management [81. Serum ferritin has in
deferiprone (DFP) and Deferasirox (DFX). general been found to correlate with body
The first drug available for treatment of iron stores [82]. After approximately one
iron overload was deferoxamine (DFO), an year of transfusions, iron begins to be
hexadentate iron chelator that is not orally deposited in parenchymal tissues [83].
absorbed and thus needs parenteral Morbidity and mortality are now the result
administration, usually as a subcutaneous of chronic transfusion induced iron
8- to 12-hour nightly infusion, 5-7 nights a overload and most patients die of heart
week. Average dosage is 20-40 mg/kg dysfunction of iron deposition [84]. Iron
body weight for children and 30-50 mg/kg accumulation in the liver causes fibrosis
body weight for adults [76, 77]. Second and cirrhosis [85]. Endocrine abnormalities
drug deferiprone (DFP), orphan drug is an related to iron overload include diabetes
orally active iron chelator which has mellitus and impaired glucose tolerance,
emerged from an extensive search for new adrenal insufficiency, hypothyroidism,
treatment of iron overload. Comparative osteoporosis, hypoparathyroidism and
studies have shown that this chelator, at hypogonadism [85]. In most studies, bone
doses of 75-100 mg/kg/day may be as density is markedly reduced (cause
effective as DFO in removing body iron osteoporosis) in patients with β-
[78]. Third drug, Deferasirox (DFX) is a thalassemia, particularly those with
once-daily, orally administered iron hypogonadism. Osteopenia may be related
chelator that a large program of clinical to marrow expansion, even in patients who
trials has shown to be effective in adults receive transfusions, [86] or to iron induced
and children [79, 80]. It received European osteoblast dysfunction, diabetes,
Union marketing authorization as an hypoparathyroidism, or hypogonadism
orphan drug from the EMEA in 2002 and [87]. Indications for splenectomy are
was authorized for marketing in most symptoms of splenic enlargement,
countries in 2006. leukopenia and/or thrombocytopenia and
Complications increasing iron overload despite good
In developed countries, patients are given chelation [88].
routine transfusion therapy, which has Conclusion
lengthened survival and altered the clinical Thalassemia are inherited disorder; beta
course of the disease. To prevent thalassemia has high severity, presented by
alloimmunization extended blood grouping mild to severe anemia. Diagnosis by
including Complete Rh, Kell, Duffy, Kidd Complete blood count (CBC), Blood
along with ABO grouping should be done smear, Iron studies, Hemoglobinopathy,
and identical blood is transfused after DNA analysis (Genetic testing), and
Medico Research Chronicles, 2017

proper cross matching to the transfusion Prenatal testing (Genetic testing

dependent thalassemic patients [62]. of amniotic fluid). Treatment of
Patients maintained on a regular Individuals with severe anemia is via
transfusion regimen progressively develop regular blood transfusion, iron chelation,
clinical manifestations of iron overload: splenectomy, and bone marrow transplant.
hypogonadism (35-55% of the patients), Prevention is by premarital screening,
hypothyroidism (9-11%), carrier detection and prenatal testing. The
hypoparathyroidism (4%), diabetes (6- prognosis of β thalassemia major was very
10%), liver fibrosis, and heart dysfunction grim with no treatment; the natural history
(33%) [40,41]. Iron overload of tissue with was for death by age five from infections
or without transfusion is fatal, which is the and cachexia. Survival was prolonged by
most important complication of β- transfusion and chelation therapy into the
thalassemia if not prevented or adequately second decade, but it is evident that the

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