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Pustika Amalia WahidiyatHematology-Oncology Division
Cipto Mangunkusumo Hospital
Thalassemia and Hemoglobinopathia
UIN Syarif Hidayatullah, 4 Mei 2010
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Definition
Normal Hemoglobin: heme (Fe) and globin chain: -
chain and - chain
Hb fraction:
HbF (fetus)
HbA (adult)
HbA2
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Thalassemia
A genetic disorders in which the production of normal
hemoglobin is partly or completely suppressed because of
defective synthesis of one or more globin chains type of
thalassemia (thalassemia and thalassemia )
Hemoglobinopathy
Abnormal hemoglobins differ from normal hemoglobin in
structure and behaviour.
The important are: Hemoglobin S (HbS), Hemoglobin E (HbE),
Hemoglobin C (HbC), Hemoglobin O, Hemoglobin Lepore, etc
Definition
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Epidemiology
WHO 2001:
7 % from total world populations thalassemia carrier
300-400 thousands thalassemic baby/year
In the world :
200 kinds of thalassemia mutation and 100 kinds ofthalassemia mutation
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Geographic Distribution of Thalassemiain The World
Indonesia
Thalassemia belt
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Thalassemia carrier :
Thalassemia : 3 - 5%, some places: 10%
Thalassemia : 2,6 - 11%
Hemoglobin E : 1,5 - 36% (thalassemia
)
Kind of mutations :
9 thalassemia (4 deletions dan 5 non-deletions)
28 thalassemia
Common: THALASSEMIA HbE combination
In Indonesia:
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Carrier Frequency of One Gene Deletion-Thalassemia in Indonesian Population
0.3
TBS0.3 Java
0.3
Malay
O.2
Karo
O.15
0.3
0.6Toraja
Kajang
0.650.6
Mandar
0.1
Makasarese
0.7
0.1
3.7 4.2
Sumba(Kodi+Waingapu)
12.893.7
Ita Nainggolan, 2003
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CarrierThalassemia
MajorNormal Carrier
Parents
Carrier ParentsCarrier ParentsCarrier
Parents
Carrier
CarrierNormal
Mendel Law
Autosomal
recessive
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_ Thalassemia major:transfusion dependent
_ Thalassemia intermedia: milder clinical symptoms,
NOT require regular blood transfusion
_ Thalassemia minor/trait: asymptomatic
Clinically (Phenotype)
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Thalassemia
Depend on the type of mutation, leading from a
mild (++, +) to severe (0) form. The specific genetic mutations (genotypes)
correlated with clinical severity of the disease
(phenotypes).
Different countries have their own characteristicgene combinations and most frequent mutations.
Genotype
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Thalassemia 1. -thal 2/silent carrier state: onegene deletion
2. -thal 1/ -thal carrier:twogenes deletionclinically: mild anemia
3. HbH disease: threegenes deletion clinically:moderate hemolytic anemia, splenomegaly
4. Hydrops foetalis/ Hb Barts: fourgenesdeletion: death in utero
Genotype
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Eleftheriou A . TIF pub licat ion s 2003
The sites of erythropoiesis during development and differentglobins produced at each stage
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Oliv ieri NF. NEJM 1999;341:99-109
Pathophysiology of Thalassemia-
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Normal
Death during fetal life Hydrops fetalis
HbH disease Mild to severe anemia
--/-- - -/-
4=HbBart 4=HbH
Thalassemia-
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1. Chronic pale
2. Organomegaly/splenomegaly
3. Jaundice4. Bone changes
5. Facial changes
6. Hyperpigmentation
7. Family history (+)
Diagnosis
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Organomegaly Facial changesor
Facies Cooley
Clinical Features
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Blood examinations:
CBC: Hb , MCV , MCH , MCHC ,
Rt , RDW
Blood smear: microcytic, hypochromic,
anisocytosis, poikilocytosis, target cells,fragmented cells, normoblast +
Diagnosis
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Normal peripheralblood
Irondeficiency
Thalassemia major
Thalassemiaminor
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Regular blood transfusion
DrugsFolic acid
Vitamin E
Vitamin C, only used with DFO
Chelating agent
Treatment
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Chelating agent(lifetime)
Time:
Ferritin level 1000 ng/mL or
10-20 x transfusions or 3-5 L blood
Route:
Subcutaneous : Deferroxamine 20-50 mg/kg/day,
8-12 hours, 5-7 x/week.
Oral : Deferiprone 3x/day or Deferasirox single dose
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Deferiprone (L1) Deferasirox (ICL 670)
75-100 mg/kgbw/day 20-30 mg/kgbw/day
Oral chelating agents
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Splenectomy
Criteria:
A massive splenomegaly
Increase amount of blood transfusion: > 200-220
mL/kg/year
Age: > 5 years
Be careful with thrombocytosis and infection
Immunizations are important
Treatment
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Psychosocial supportPatientPhysical changes inferior
Boring & tired of medical treatmentHard to find friends
Family Embarrassed
Material burden (200-300 millions Rp/year/patient)
Treatment
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