Kuliah Hemoglobinopati.uin Syarif Hidayatullah.mei 2010 (2)

7/30/2019 Kuliah Hemoglobinopati.uin Syarif Hidayatullah.mei 2010 (2)

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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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Kuliah Hemoglobinopati.uin Syarif Hidayatullah.mei 2010 (2)

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