Thalassemiafinal 111212142013 Phpapp02 130321172427 Phpapp01

INTRODUCTION
 Thalassemia is an inherited autosomal recessive

blood disorder.
 which results in excessive destruction of red
blood cells and further leads to anemia.
 It is caused by variant or missing genes that affect
how the body make haemoglobin.
 People with thalassemia make less haemoglobin
and fewer circulating red blood cells than normal
,result in mild or severe anemia.
ALPHA
THALASSEMIA
THALASSEMA
BETA
THALASSEMIA
Alpha Thalassemia
 Alpha thalassemia is the result of changes in the

genes for the alpha globin component in hemoglobin.
 The worldwide distribution of inherited Alpha-
Thalassemia is corresponding to areas of Malaria
exposure.
ETIOLOGY
 Mutation in the DNA of cells that produce

hemoglobin
 It is a form of thalassemia involving the
genes HB1 and HB2
 It is most commonly inherited in a
Mendelian recessive fashion
PATHPHYSIOLOGY
 Alpha thalassemia results when there is

disturbance in production of α-globin from any
or all four of the α-globin genes.
 Genes are responsible for regulating the
synthesis and structure of different globins which
are divided into 2 clusters.
 The α-globin genes are encoded on chromosome
16 and the γ, δ, and β-globin genes are encoded
on chromosome 11
 A normal person carries a linked pair of alpha
globin genes, 2 each from maternal and paternal
chromosome.
 Therefore, alpha thalassemia occurs when there
is a disturbance in production of α-globin from
any or all four of the α-globin genes.
 When functional point mutations, frame shift
mutations, nonsense mutations, and chain
termination mutations occur within or around the
coding sequences of the alpha-globin gene
cluster hemoglobin is impaired.
 When that occurs, protein synthesis may be
inhibited.
 Normal production of alpha chains is absent which
results in excess production of gamma- globin chains in
the fetus and newborn or beta- globin chains in children
and adults.
 The β-globin chains are capable of forming soluble
tetramers (beta-4, or HbH)
 This form of hemoglobin is still unstable and precipitates
within the cell, forming insoluble inclusions called Heinz
bodies
 These Heinz bodies damage the red blood cells.
 This further results in damage to erythrocyte precursors
and ineffective erythropoiesis in the bone marrow,
hypochromia and microcytosis of circulating red blood
cells
CLINICAL PRESENTATION
 Shortage of red blood cells- Anemia
 Pale skin
 Weakness
 Fatigue
 Enlarged liver and spleen- hepatosplenomegaly
 Heart defects
 Abnormalities of the urinary system or genitalia
 Hb Bart syndrome can cause complications in pregnancy such
as
 High blood pressure
 Premature delivery
 Abnormal bleeding
 Jaundice
Treatment of Alpha Thalassemia
 Treatment for thalassemia often involves regular
blood transfusions and folate supplements.
 If you receive blood transfusions, you should not take
iron supplements. Doing so can cause a high amount
of iron to build up in the body, which can be harmful.
 Persons who receive significant numbers of blood
transfusions need a treatment called chelation therapy
to remove excess iron from the body.
 Bone marrow transplant may help treat the disease in
some patients, especially children.
Surgical Treatment
Perform splenectomy if transfusion
requirements are increasing.
Surgical or orthodontic correction may
be necessary to correct skeletal
deformities of the skull and maxilla
caused by erythroid hyperplasia.
DEFEROXAMINE - INJECTION
Medications
FOLIC ACID- ORAL
FOLIC ACID - INJECTION
FOLIC ACID - ORAL
 BRAND NAME(S): FA-8
 USES
 Folic acid is the man-made form of folate which is a
B6-vitamin naturally found in some foods.
 It is needed to form healthy cells, especially red
blood cells.
 Active forms of folic acid are: L-methylfolate and
levomefolate
 Folic acid supplements are used to treat or prevent
low folate levels.
SIDE EFFECTS
Folic acid usually has very few side

effects
Possible side effects include:
Serious allergic reaction, including:
rash, itching/swelling (especially of
the face/tongue/throat), dizziness,
trouble breathing
Folic acid is safe to take during pregnancy
when used as directed. It is included in
prenatal vitamin products.
Certain spinal cord birth defects may be
prevented by taking adequate amounts of
folic acid during pregnancy.
Beta Thalassemia
 Specifically, it is characterized by a
genetic deficiency in the synthesis
of beta- globin chains.
 Beta-globin is a component
(subunit) of hemoglobin.
Types
Thalassemia Major
(Cooley's anemia)
Thalassemia Minor
-severe form of beta
thalassemia - presence of one normal
gene and one with a
- presence of two mutation
abnormal genes that
cause either a severe - causes mild to
decrease or complete moderate mild
lack of beta globin anemia.
production.
ETIOLOGY
Beta thalassemia is caused by a deficiency of Beta
globin inherited in an autosomal recessive
pattern, which means both copies of the
HBB(Hemoglobin beta) gene in each cell have
mutations.
The parents of an individual with an autosomal
recessive condition each carry one copy of the mutated
gene, but they typically do not show signs and
symptoms of the condition.
Etiology-cont’d
 A lack of beta-globin leads to a reduced amount of functional
hemoglobin. Without sufficient hemoglobin, red blood cells
do not develop normally, causing a shortage of mature red
blood cells.
 The low number of mature red blood cells leads to anemia
and other associated health problems in people with beta
thalassemia.
Clinical Presentations
Thalassemia minor- characterized by mild anemia
Symptoms of beta thalassemia major appear in the first two years
of life.
 Fatigue and weakness
 Pale skin or jaundice (yellowing of the skin)
 Protruding abdomen with enlarged spleen and liver
Clinical Presentations
 Dark urine
 Abnormal facial bones and poor growth
 A poor appetite.
 Adolescents with the severe form of beta
thalassemia may experience delayed puberty.
PATHOPHYSIOLOGY
 In Beta thalassemia major, patients have severe anemia, ineffective
erythropoiesis, extramedullary hematopoiesis, and iron overload
resulting from transfusion and increased iron absorption.
 The skin may show pallor from anemia and jaundice from
hyperbilirubinemia.
 The skull and other bones may be deformed secondary to erythroid
hyperplasia with intramedullary expansion and cortical bone
thinning.
 Heart examination may reveal findings of cardiac failure and
arrhythmia, related to either severe anemia or iron overload.
 Abdominal examination may reveal changes in
the liver, gallbladder, and spleen.
 Patients who have received blood transfusions
may have hepatomegaly or chronic hepatitis due
to iron overload.
 The gallbladder may contain bilirubin stones
formed as a result of the patient's lifelong
hemolytic state.
Pathophysiology- Cont’d
 Splenomegaly typically is observed as part of the

extramedullary hematopoiesis or as a hypertrophic
response related to the extravascular hemolysis.
 In addition to cardiac
dysfunction, hepatomegaly, and hepatitis, iron
overload can also cause endocrine
dysfunction, especially affecting the
pancreas, testes, and thyroid.
 Transfusion-associated viral hepatits resulting in
cirrhosis or portal hypertension also may be seen.
Surgical Treatment
Splenectomy- decrease transfusion requirements

Cholecystectomy- Patients with thalassemia
minor may have bilirubin stones in their
gallbladder and, if symptomatic, may require
treatment. Perform a cholecystectomy using a
laparoscope or carry out the procedure at the
same time as the splenectomy.
TREATMENT
Treatment for beta thalassemia involves iron chelation.

1. Deferoxamine
2. Deferasirox
CURATIVE METHOD
BMT FROM COMPATIBLE BMT FROM HAPLOIDENTICAL

DONOR MOTHER TO CHILD
 Free survival 87%  Free survival 70%
 Rejection 10%  Rejection 23%
 Mortality 3%  Mortality 7 %
EPIDEMIOLOGY
References
 American College of Obstetricians and Gynecologists (ACOG). Hemoglobinopathies in Pregnancy. ACOG Practice Bulletin, number 78, January 2007.
 Beta Thalassemia. (Sept 2, 2011). Retrieved from http://emedicine.medscape.com/article/206490-overview
 Bleibel, S. et al. Thalassemia, Alpha. Retrieved: 29 September, 2011 from http://emedicine.medscape.com/article/206397-overview#a0104
 Cohen, A.R., et al. Thalassemia. Hematology 2004, American Society of Hematology, pages 14-34.
 Cooley’s Anemia Foundation. About Thalassemia. Updated 2007.
 Cunningham, M.J. Update on Thalassemia: Clinical Care and Complications. Pediatric Clinics of North America, volume 55, April 2008, pages 447-460.
 Deferoxamine [Pharm GKB]. (n.d.). Retrieved from http://www.pharmgkb.org/do/serve?objId=PA164746490&objCls=Drug#tabview=tab1
 Di Bartolomeo, P., et al. Long-term Results of Survival in Patients with Thalassemia Major Treated with Bone Marrow Transplantation. American Journal of
Hematology, February 13, 2008 (Epub ahead of print).
 Exjade (Deferasirox) Drug Information… (Aug 19, 2011). Retrieved from http://www.rxlist.com/exjade-drug.htm
 Food and Drug Administration (FDA). FDA Approves First Oral Drug for Chronic Iron Overload. FDA News, November 9, 2005
 Food and Drug Administration (FDA). FDA Approves First Oral Drug for Chronic Iron Overload. FDA News, November 9, 2005.
 Linda J. Vorvick, MD, Medical Director, MEDEX Northwest Division of Physician Assistant Studies, University of Washington, School of Medicine; and Yi-Bin
Chen, MD, Leukemia/Bone Marrow Transplant Program, Massachusetts General Hospital; and David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc., Review
Date: 1/31/2010,Thalassemia, retrieved on 2011-09-30, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001613/
 Lucile Packard Children’s Hospital at Standford. 2011. Alpha Thalassemia. Retrieved: 29 September, 2011 from http://www.lpch.org/DiseaseHealthInfo/HealthLibrary/hematology/thalapth.htmlth

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INTRODUCTION

 Thalassemia is an inherited autosomal recessive

 Alpha thalassemia is the result of changes in the

 Mutation in the DNA of cells that produce

 Alpha thalassemia results when there is

 BRAND NAME(S): FA-8

Folic acid usually has very few side

 Splenomegaly typically is observed as part of the

Splenectomy- decrease transfusion requirements

Treatment for beta thalassemia involves iron chelation.

BMT FROM COMPATIBLE BMT FROM HAPLOIDENTICAL

 Free survival 87%  Free survival 70%

 Rejection 10%  Rejection 23%

 Beta Thalassemia. (Sept 2, 2011). Retrieved from http://emedicine.medscape.com/article/206490-overview

 Bleibel, S. et al. Thalassemia, Alpha. Retrieved: 29 September, 2011 from http://emedicine.medscape.com/article/206397-overview#a0104

 Cooley’s Anemia Foundation. About Thalassemia. Updated 2007.

 Deferoxamine [Pharm GKB]. (n.d.). Retrieved from http://www.pharmgkb.org/do/serve?objId=PA164746490&objCls=Drug#tabview=tab1

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