See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/274082074

The Thalassemias

Chapter · December 2014

DOI: 10.1016/B978-0-12-801238-3.05342-3

CITATIONS READS

0 2,117

2 authors:

Van Do Hoang Tran

Bridgeport Hospital University of Massachusetts Medical School
12 PUBLICATIONS   74 CITATIONS    34 PUBLICATIONS   133 CITATIONS   

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Self-managment in individuals with chronic complex conditions View project

Length of stay View project

All content following this page was uploaded by Hoang Tran on 16 November 2017.

The user has requested enhancement of the downloaded file.

 The Thalassemias☆
PT Silberstein, Creighton University School of Medicine, Omaha, NE, USA
Van Do and H Tran, University of Nebraska Medical Center, Omaha, NE, USA
ã 2014 Elsevier Inc. All rights reserved.

Introduction 1
Definition 1
Classification 1
Alpha Thalassemia 1
Beta Thalassemia 2
Consequences 2
Associated Disorders 2
Psychological impact of thalassemia 3
Etiology 3
Epidemiology 3
Pathophysiology 3
Signs and Symptoms 4
Treatment 4
Blood transfusion 4
Hematopoietic stem cell transplant 4
Gene therapy 4
References 5

Introduction

The thalassemias refer to a syndrome of diseases characterized by decreased or absent production of one or more globin chains.
Beta thalassemia is due to deficient production of beta globin chains, which causes a relative excess of alpha globin chains. These
excess alpha globin chains are insoluble and precipitate within the red cell, leading to a variety of clinical manifestations. The
severity of subsequent clinical manifestations depends on the degree of alpha globin chain excess. The symptoms are severe in
patients homozygous for impaired beta globin synthesis and much less severe in heterozygotes, who generally have mild anemia
and no symptoms.
Alpha thalassemia is due to decreased production of alpha globin chains, resulting in a relative excess of beta globin chains.

Definition

The thalassemias are hereditary disorders characterized by a decrease in the synthesis of globin chains (alpha or beta). Impaired
globin chain synthesis causes impaired production of hemoglobin and eventually results in a hypochromic microcytic anemia
because of defective hemoglobinization of the red blood cells (Weatherall, 2010a, 2010b).

Classification

Thalassemia is due to decreased production of one or more globin chains. The most important types are those that affect either
alpha or beta chain synthesis.

Alpha Thalassemia

There are several forms of alpha thalassemia. The most common forms are:
Silent carrier alpha thalassemia: There are two alpha genes located on each chromosome 16. In the silent carrier state, one of the
alpha genes is absent, leaving three of four genes (aa/ao). Patients are hematologically healthy, except for occasional low red blood
cell indices.

☆
Change History: July 2014. PT Silberstein, Van Do and H Tran introduced small edits in the text of the article including citations and table.

Reference Module in Biomedical Research http://dx.doi.org/10.1016/B978-0-12-801238-3.05342-3 1

2 The Thalassemias

Alpha thalassemia trait: This form is usually caused by the deletion of two alpha (a) genes on one chromosome 16 (aa/oo) or
the deletion of one gene from each chromosome 16 (ao/ao). Alpha thalassemia trait is more common in Southeast Asia, the Indian
subcontinent, and some parts of the Middle East. This trait is characterized by mild anemia and low red blood cell indices.
Hb H disease: This form results from the deletion or inactivation of three alpha globin genes (oo/ao), resulting also in an excess
of beta chains. Patients usually present with severe anemia, splenomegaly, icterus, and abnormal red blood cell indices.
Alpha thalassemia major: This condition results from the deletion of all alpha genes on both copies of chromosome 16 (oo/oo),
leading to the severe form of homozygous alpha thalassemia. This condition is usually incompatible with extrauterine life and
results in hydrops fetalis and death shortly after delivery unless intrauterine blood transfusion is given (Longo, 2012a,b, Damon
and Charalambos Andreadis, 2014a,b).

Beta Thalassemia

In contrast to the duplication found in alpha thalassemia, there is only one beta-globin gene on chromosome 11. There are several
forms of beta thalassemia:
Silent carrier beta thalassemia or beta thalassemia minor: The mutation that causes this form of thalassemia is very mild. These
patients usually have no signs or symptoms, or have some minor changes in number or size of the red blood cell. This is the most
common form of beta thalassemia.
Beta thalassemia trait or beta thalassemia intermediate: In this condition, the production of beta globin is decreased. Patients
have mild anemia, abnormal red blood cell indices, and abnormal hemoglobin electrophoresis results with elevated levels of Hb
A2, Hb F, or both.
Thalassemia major (Cooley’s anemia): In this condition, the patient can’t produce beta globin. To compensate, the marrow
produces gamma globin and more alpha globin. This condition is characterized by transfusion-dependent anemia, massive
splenomegaly, bone deformities, growth retardation, and peculiar facies in untreated individuals. Hemoglobin electrophoresis
shows high level of Hb A2, Hb F, and no Hb A (Longo, 2012a,b, Damon and Charalambos Andreadis, 2014a,b).

Consequences

Alpha thalassemia major resulting in hydrops fetalis is usually a fatal disease. The treatment is in utero transfusion for the fetus.
These patients require extensive blood transfusions and chelation therapy. In utero hematopoietic cell transplantation was also
applied for patients with alpha thalassemia major(Thornley et al., 2003). However, this procedure has not been proved effective in
human except in cases of immunodeficiencies due to the host hematopoetic competition (Touraine et al., 2004, Nijagal
et al., 2012).
Hb H disease: Depending on the severity of the condition, patient may require frequent or occasional blood transfusions. Some
patients may require splenectomy. Morbidity is usually related to anemia, complications of blood transfusions, massive spleno-
megaly or complications of splenectomy.
In patients with various types of beta thalassemia, mortality and morbidity vary according to the severity of the disease and the
quality of care provided. Severe cases of beta thalassemia major are fatal if not treated. Major causes of morbidity and mortality are
secondary to complications of anemia, multiple blood transfusion and iron overload. For example, heart failure due to severe
anemia or iron overload is a common cause of death. Liver disease could also be secondary to iron overload. Multiple transfusions
could predispose to infections and can also result in iron overload.

Associated Disorders

Multiple blood transfusions result in iron overload, which can cause secondary hemosiderosis. Cardiac involvement is a major
cause of death in patients with thalassemia. Transfusional hemosiderosis has been classified into 3 stages based on the number of
blood units given. The higher the number of packed red blood cells units given, the more advanced the stage. Advanced stage is
associated with more severe clinical symptoms and more abnormal cardiac functions.
Patients who have received regular blood transfusions sometimes develop liver enlargement due to swelling of the phagocytic
and parenchymal cells from the deposition of hemosiderin.
Calcified bilirubin stones are common in patients with beta thalassemia major.
People with thalassemia major frequently exhibit features of diabetes mellitus. This could be due to defective pancreatic
production of insulin, but insulin resistance has also been implicated.
Adult patients with thalassemia major are known to have low fertility; this is attributed to the commonly encountered
hypogonadotrophic hypogonadism.
People with thalassemia, especially with thalassemia intermediate, have higher risk of thromboembolism event as compared to
the general population (Sirachainan, 2013).
 The Thalassemias 3

Children or young adults with thalassemia usually present with osteopenia or osteoporosis despite adequate transfusion and
iron chelation therapy. The mechanism for osteopathy in thalassemia patient is complex. Osteoporosis reduces bone strength and
increases risk of skeletal abnormalities, fractures, spinal deformities, nerve compression, and growth failure (De Sanctis
et al., 2013).

Psychological impact of thalassemia

Having thalassemia is a burden for the patient and his family. Lifelong treatment with increasing risk of comorbidity and
complications over time affects patient’s mental health. An observational study has showed higher rate of psychiatric disorder in
thalassemia patients as compared to the general population (Mednick et al., 2010). Patients with thalassemia major have higher
prevalence of psychiatric disorders, and therefore, are likely to exhibit lower treatment adherence. Psychological disorders range
from anxiety, depression, attention-deficit hyperactivity disorder, to bipolar mood disorder. Ghanizadeh found more than 43% of
the patients with thalassemia had recurrent thoughts of suicide and 27.3% had considered suicide in the last year
(Ghanizadeh, 2006).

Etiology

Thalassemia is due to decreased production of at least one globin polypeptide chain (beta, alpha, gamma, delta) which results in
unbalanced hemoglobin synthesis. Inheritance of thalassemia is autosomal recessive.
Beta Thalassemia results from decreased production of beta-polypeptide chains. Heterozygotes are carriers and have asymp-
tomatic mild to moderate microcytic anemia (thalassemia minor). Homozygotes (beta-thalassemia major or Cooley’s anemia)
develop severe anemia and bone marrow hyperactivity.
Alpha thalassemia is a result of decreased production of alpha globins. Heterozygotes for a single gene defect results in silent
alpha thalassemia state. Heterozygotes with defects in two of the four genes result in alpha thalassemia trait, and tend to develop
mild to moderate microcytic anemia but with no symptoms. Defects in three of the four genes more severely impair alpha-chain
production, resulting in the formation of tetramers of excess beta chains (HbH) or, in infancy, gamma chains (Bart’s Hb). Defects in
all four genes are a lethal condition unless given blood transfusions in utero, because hemoglobin that lacks alpha chains does not
transport oxygen.
Another thalassemia form is hemoglobin E (Hb E) related. Hb E, one of the most common hemoglobinopathies, is due to
missense mutation in codon 26 which belongs to splicing sequence of Beta globin gene. This mutation not only affects structure but
also reduces the production rate of beta globin. As consequence, Hb E trait and disease usually present with mild Beta thalassemia
phenotype. Co-inheritance of Hb E and thalassemia is commonly found in Southeast Asia, India and Bangladesh (Sharma et al.,
2013). This compound heterozygote state of Hb E/Thalassemia results in a variable phenotype ranging from mild anemia to
transfusion dependency (Olivieri et al., 2010). The most significant genotype is Hb E/Beta thalassemia which accounts for 50% of
severe beta thalassemia worldwide (Fucharoen and Weatherall, 2012). Patients with Hb E/Beta thalassemia have a higher risk of
pulmonary hypertension or vitamin D deficiency (Atichartakarn et al., 2014, Nakavachara and Viprakasit, 2013).

Epidemiology

The alpha thalassemia syndromes are seen primarily in persons from Southeast Asia and China, and less commonly, in African
Americans.
Beta thalassemia primarily affects persons of Mediterranean origin (Italian, Greek) and to a lesser extent Chinese, other Asians,
and blacks.

Pathophysiology

The imbalance in globin chain synthesis is the basic defect in all types of thalassemia.
In alpha thalassemia, there is an excessive production of gamma chains in the fetus and newborn and beta chains later in life.
These chains are relatively soluble and able to form homotetramers. These homotetramers, although relatively unstable, remain
able to produce soluble hemoglobin molecules such as hemoglobin Bart (four gamma chains) and hemoglobin H (four beta
chains) both of which are nonfunctional hemoglobins because of insufficient number of alpha globin chains.
In beta thalassemia, there is accumulation of alpha chains in the red blood cell precursors. These chains are insoluble,
precipitate in the cell, interact with the membrane resulting in significant damage, and interfere with cell division. This leads to
excessive intramedullary destruction of the red blood cell precursors. In addition, the insoluble chains accumulate and precipitate
in the red blood cell causing inclusion bodies and resulting in hemolysis and destruction of red blood cells. This means that both
hemolysis and ineffective erythropoiesis cause anemia in individuals with beta thalassemia (Rund and Rachmilewitz, 2005).
4 The Thalassemias

Signs and Symptoms

The symptoms of thalassemia depend on the genetic defect and its severity. The more severe the genetic defect, the less hemoglobin
is produced and the more severe the anemia that results. Thalassemia minor is usually silent and usually causes no symptoms. If it
does, the most common symptom is mild anemia. Thalassemia major usually has severe hemolytic anemia. The symptoms of
thalassemia major may include:

• Fatigue
• Failure to thrive
• Jaundice
• Enlarged spleen and liver
• Bony abnormalities, especially of the facial bones Pale skin

Treatment

Standard therapy includes blood transfusions, folic acid, iron chelating agents, and hematopoietic cell transplant. Treatment
choices depend on the patient’s clinical manifestation.

Blood transfusion

Blood transfusion indication is mandatory for patients with beta thalassemia major but is still controversial for whom with
intermediate. Though blood transfusion can prevent serious complications, it increases morbidity due to accumulation of
transfused complications. The common approach is to delay transfusion until the patient demonstrates complications of anemia.
A recent study indicated that initiation of chronic transfusion after 12 year of age increased the risk of thromboembolic event,
pulmonary hypertension, silent brain infarction and graft versus host disease as compared to giving transfusions earlier in beta
thalassemia major (Taher, 2010). Earlier transfusion combined with iron chelation therapy was recommended as a treatment of
choice to reduce late complications (Taher, 2012). In Cooley’s anemia patients, indications for chronic transfusion include
(1) hemoglobin lower than 50 (mg L 1), (2) failure to thrive, (3) severe bony deformity, (4) declining Hb concentration combined
with spleen enlargement more than 3 cm per year and (5) end organ complication. Indications for acute transfusion include
(1) pregnancy, (2) infection and (3) perioperative (Taher, 2012).

Hematopoietic stem cell transplant

Hematopoietic stem cell transplant (HSCT) is currently the only curative treatment for beta thalassemia major. HSCT replaces the
impaired endogenous hematopoietic cells with effective allogeneic alternatives to permanently produce normal red blood cells.
Transplanted patients do not need blood transfusion and avoid consequent iron accumulation complications. On the other hand,
side effects after HSCT include graft-versus host diseases, infections related to abnormal immune reconstitution, tissue dysfunction,
secondary cancers, and changes in quality of life (Montebugnoli et al., 2011). In spite of a transplant-related mortality of 5%-10%,
patients with an HLA-matched sibling or related donor have a long-term cumulative survival rate of 80%-90% in most studies (Di
Bartolomeo et al., 2008, Lucarelli and Gaziev, 2008). While allogeneic HSCT is often limited by a lack of suitable donors, new
protocol recently allows transplant with unrelated donor. Recent studies indicate the outcome of unrelated donor transplant in
patients with beta thalassemia major is comparable with that of transplant from identical family donors (La Nasa et al., 2005, Li
et al., 2012). In the long-term, beta thalassemia major patients treated with HSCT can attain higher health-related quality of life
(HRQoL) than that with conventional treatments. Moreover, transplanted patients have similar HRQoL with the general popula-
tion (La Nasa et al., 2013).

Gene therapy

Gene therapy holds promise repairing one’s own bone marrow cells by transferring the normal b-globin or g-globin gene into
hematopoietic stem cells (HSCs) to provide permanent erythropoietic effect. Since 2000, the introduction of gene transfer using
lentiviral vectors has succeeded to repair beta thalassemia gene in a mouse model. However, the oncogenic risk of lentiviral vector
integration is a long-term concern. A recent study reported safe mobilization of CD34+ cells in adults with beta thalassemia and
validated the effectiveness of globin gene transfer for clinical investigation (Boulad et al., 2014). For the first time, a patient with
severe beta-thalassemia has been independent from transfusion for 5 years after gene therapy (Tubsuwan, 2013). The first clinical
trial of gene therapy in US with three patients is in the first phase. The patients well tolerated with cytoreduction and recovered their
blood counts although they were still dependent on blood transfusion (Riviere et al., 2013; Table 1).
 The Thalassemias 5

Table 1 Major medications

Agent name Discussion

Iron chelating These agents are used to chelate excessive iron from the body in patients with iron overload. Iron chelation therapy may be
agents indicated if serum ferritin concentrations exceed 1000 (ngml 1)
Deferoxaminemesylate chelates iron from ferritin or hemosiderin but not from transferrin, cytochrome, or Hb. The dose in adults
is 20–40 20 (mg kg 1 day 1)s.c. with infusions through infusion pump over 8–12 H. After blood transfusion, administration of
1–2 g i.v. at a slow rate of 15 20 (mg kg 1 h 1) is given. Although deferoxamine is absorbed orally, the pharmacokinetics of
intermittent oral doses is unfavorable for effective iron chelation. It has a short half-life, and as a result, it is necessary to be
given as an infusion
Deferasirox (Exjade) is an iron-chelating agent that is given orally to decrease transfusional iron overload. The Initial adult dose is
20 (mg kg 1) orally daily. The dose should be calculated to the nearest whole tablet (Exjade is available in 125 (mg), 250 (mg),
and 500 (mg) tablets). The dose could be adjusted every three to six months by increments of 5–10 (mg kg 1) based on ferritin
level. A dose above 30 (mg kg 1) is not recommended due to limited experience. If the serum ferritin level falls consistently
below 500 (mcg L 1), consider holding the treatment
Deferiprone (Ferriprox) is an oral iron chelator, approved by FDA in 2011, mainly indicated in patients with deferoxamine
noncompliance. The recommended initial dose is 25 (mg kg 1) three time per day (totally 75 (mg kg 1) per day). The maximum
dose is 99 to 100 (mg kg 1) per day. Neutrophil and granulocyte need to be monitored closely. If the serum ferritin level falls
consistently below 500 (mcg L 1), consider holding the treatment
Antipyretics Administration of antipyretic drugs such as non-steroidal anti-inflammatory drugs and acetaminophen before blood transfusion
prevents or decreases febrile reactions
Vitamins Folic acid is needed due to increased utilization secondary to the hemolytic process
Hydroxyurea Cytotoxic drug commonly used in the treatment of myeloproliferative disorders, has been shown to reduce need of blood
transfusion for both alpha and beta thalassemia patients (Bradai et al. 2007, Koren et al. 2008)
Antihistamines Antihistamines, such as diphenhydramine, are usually administered prior to blood transfusion to decrease or prevent mild allergic
reactions
Vaccines Splenectomized patients are particularly susceptible to infections with the encapsulated organisms such as pneumococci,
haemophilus influenza, and meningococcal organisms. As a result, such patients now are immunized against these organisms
1–2 weeks prior to the procedure to prevent infections

References
Atichartakarn V, Chuncharunee S, Archararit N, Udomsubpayakul U, Lee R, Tunhasiriwet A, and Aryurachai K (2014) Prevalence and risk factors for pulmonary hypertension in patients
with hemoglobin E/beta-thalassemia disease. European Journal of Haematology 92(4): 346–353.
Bradai M, Pissard S, Abad MT, Dechartres A, Ribeil JA, Landais P, and de Montalembert M (2007) Decreased transfusion needs associated with hydroxyurea therapy in Algerian
patients with thalassemia major or intermedia. Transfusion 47(10): 1830–1836.
Boulad F, Wang X, Qu J, Taylor C, Ferro L, Karponi G, Bartido S, Giardina P, Heller G, Prockop SE, Maggio A, Sadelain M, and Riviere I (2014) Safe mobilization of CD34 + cells in
adults with beta-thalassemia and validation of effective globin gene transfer for clinical investigation. Blood 123(10): 1483–1486.
Longo DL (2012a) Part 7: Oncology and Hematology. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Larry Jameson J, and Loscalzo J (eds.) Harrison’s Principles of Internal
Medicine, 18e United States of America: The McGraw-Hill Companies, Inc.
De Sanctis V, Soliman AT, Elsedfy H, Yassin M, Canatan D, Kilinc Y, Sobti P, Skordis N, Karimi M, Raiola G, Galati MC, Bedair E, Fiscina B, and El Kholy M (2013) Osteoporosis in
thalassemia major: an update and the I-CET 2013 recommendations for surveillance and treatment. Pediatric Endocrinology Reviews: PER 11(2): 167–180.
Di Bartolomeo P, Santarone S, Di Bartolomeo E, Olioso P, Bavaro P, Papalinetti G, Di Carlo P, Papola F, Nicolucci A, Di Nicola M, and Iacone A (2008) Long-term results of survival in
patients with thalassemia major treated with bone marrow transplantation. American Journal of Hematology 83(7): 528–530.
Fucharoen S and Weatherall DJ (2012) The hemoglobin E thalassemias. Cold Spring Harbor Perspectives in Medicine 2(8): a011734. http://dx.doi.org/10.1101/cshperspect.a011734.
Ghanizadeh A (2006) “Prevalence of psychiatric disorders depression and suicidal behavior in child and adolescent with thalassemia major” Journal of Pediatric Hematology/Oncology
28: 781–784.
Koren A, Levin C, Dgany O, Kransnov T, Elhasid R, Zalman L, Palmor H, and Tamary H (2008) Response to hydroxyurea therapy in beta-thalassemia. American Journal of Hematology
83(5): 366–370.
La Nasa G, Argiolu F, Giardini C, Pession A, Fagioli F, Caocci G, Vacca A, De Stefano P, Piras E, Ledda A, Piroddi A, Littera R, Nesci S, and Locatelli F (2005) Unrelated bone marrow
transplantation for beta-thalassemia patients: The experience of the Italian Bone Marrow Transplant Group. Annals of the New York Academy of Sciences 1054: 186–195.
La Nasa G, Caocci G, Efficace F, Dessi C, Vacca A, Piras E, Sanna M, Marcias M, Littera R, Carcassi C, and Lucarelli G (2013) Long-term health-related quality of life evaluated more
than 20 years after hematopoietic stem cell transplantation for thalassemia. Blood 122(13): 2262–2270.
Li C, Wu X, Feng X, He Y, Liu H, Pei F, Liao J, He L, Shi L, Li N, Liu Q, Liu S, Chen G, Su Q, Ren Y, Wang Y, and Tan W (2012) A novel conditioning regimen improves outcomes in
beta-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation. Blood 120(19): 3875–3881.
Damon LE and Charalambos Andreadis M (2014a) Chapter 13. Blood Disorders. In: Papadakis MA, McPhee SJ, and Rabow MW (eds.) Current Medical Diagnosis & Treatment 2014
United States of America: McGraw-Hill Education, Lange Medical Publications.
Lucarelli G and Gaziev J (2008) Advances in the allogeneic transplantation for thalassemia. Blood Reviews 22(2): 53–63.
Mednick L, Yu S, Trachtenberg F, Xu Y, Kleinert DA, Giardina PJ, Kwiatkowski JL, Foote D, Thayalasuthan V, Porter JB, Thompson AA, Schilling L, Quinn CT, Neufeld EJ,
Yamashita R, and Network TCR (2010) Symptoms of depression and anxiety in patients with thalassemia: prevalence and correlates in the thalassemia longitudinal cohort.
American Journal of Hematology 85(10): 802–805.
Montebugnoli L, Gissi DB, Marchetti C, and Foschini MP (2011) Multiple squamous cell carcinomas of the oral cavity in a young patient with graft-versus-host disease following
allogenic bone marrow transplantation. International Journal of Oral and Maxillofacial Surgery 40(5): 556–558.
Nakavachara P and Viprakasit V (2013) Children with hemoglobin E/beta-thalassemia have a high risk of being vitamin D deficient even if they get abundant sun exposure: A study
from Thailand. Pediatric Blood & Cancer 60(10): 1683–1688.
Nijagal A, MacKenzie TC, and Flake AW (2012) In Utero Hematopoietic Cell Transplantation for the Treatment of Congenital Anomalies. Clinics in Perinatology 39(2): 301–310.
 6 The Thalassemias

Olivieri NF, Pakbaz Z, and Vichinsky E (2010) HbE/beta-thalassemia: Basis of marked clinical diversity. Hematology/Oncology Clinics of North America 24(6): 1055–1070.
Riviere I, Wang X, Bartido S, Prockop SE, Barone R, Moi P, Maggio A, and Sadelain M (2013) First US Phase I Clinical Trial Of Globin Gene Transfer For The Treatment Of Beta-
Thalassemia Major. Blood 122(21): 716.
Rund D and Rachmilewitz E (2005) b-Thalassemia. New England Journal of Medicine 353(11): 1135–1146.
Sharma A, Marwah S, Buxi G, and Yadav R (2013) Hemoglobin e syndromes: Emerging diagnostic challenge in north India. Indian Journal of Hematology & Blood Transfusion: An
Official Journal of Indian Society of Hematology and Blood Transfusion 29(1): 21–25.
Sirachainan N (2013) Thalassemia and the hypercoagulable state. Thrombosis Research 132(6): 637–641.
Taher AT (2010) Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: The OPTIMAL CARE study. Blood
115: 1886–1892.
Taher AT (2012) Contemporary approaches to treatment of beta-thalassemia intermedia. Blood Reviews vol. 26 (no. suppl.1): S24–S27.
Thornley I, Lehmann L, Ferguson WS, Davis I, Forman EN, and Guinan EC (2003) Homozygous alpha-thalassemia treated with intrauterine transfusions and postnatal hematopoietic
stem cell transplantation. Bone Marrow Transplantation 32(3): 341–342.
Touraine JL, Raudrant D, Golfier F, Rebaud A, Sembeil R, Roncarolo MG, Bacchetta R, D’Oiron R, Lambert T, and Gebuhrer L (2004) Reappraisal of in utero stem cell transplantation
based on long-term results. Fetal Diagnosis and Therapy 19(4): 305–312.
Tubsuwan A (2013) Parallel assessment of a globin lentiviral vector after transduction of ips and somatic hematopoietic stem cells from the same transplanted human b-thalassemia
patient. Human Gene Therapy 24(12): A46–A47.
Weatherall DJ (2010a) Chapter 47. the thalassemias: Disorders of globin synthesis. New York: McGraw-Hill Companies, Incorporated.

Book Citations.

Longo DL (2012b) Part 7: Oncology and Hematology. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Larry Jameson J, and Loscalzo J (eds.) Harrison’s Principles of Internal
Medicine, 18e United States of America: The McGraw-Hill Companies, Inc.
Damon LE and Charalambos Andreadis M (2014b) Chapter 13. Blood Disorders. In: Papadakis MA, McPhee SJ, and Rabow MW (eds.) Current Medical Diagnosis & Treatment 2014
United States of America: McGraw-Hill Education, Lange Medical Publications.
Weatherall DJ (2010b) Chapter 47. The thalassemias: Disorders of globin synthesis. In: Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K, and Prchal JT (eds.) Williams
Hematology, 8e New York, NY: McGraw-Hill.

Relevant WebSites

This article by Hassan M yaish, MD describes various aspects of thalassemias, including molecular aspects and epidemiology – http://www.emedicine.com/PED/topic2229.htm.
This subscription site is useful in getting further information on the disease – http://www.uptodate.com/.
This Merck website can be used to compare thalassemias to other anemias – http://www.merck.com/mmpe/sec11/ch131/ch131m.html.
This site gives data on Cooley’s anemia with links to descriptions of other anemias – http://www.fpnotebook.com/HEM45.htm.
This Novartis website gives clinical information on the chelating agent, deferasirox – http://www.exjade.com/index.jsp.
This website give more information of lentiviral vector of gene transportation – http://www.systembio.com/lentiviral-technology/expression-vectors.

View publication stats