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Thalassemia
...


(Hemoglobinopathy) (Thalassemia)

(Autosomal recessive) .. - (..

.. .. ) 30% (trait
heterozygote) 1%

2
1. Heme Porphyrin 4 pyrole ring
Ferroprotoporphyrin complex
2. Globin Polypeptides 1

4 2 globin 16 2
11 hemoglobin tetramer


Electrophoresis

Liquid Chromatography, Isoelectric focusing Mass Spectrophotometer

Embryo Fetus
2 16 11
(Hemoglobin switching)
2, 1, 2, 1,
- gene () Embryo 6 - 8
- gene () 2 2 gene 1 gene
embryo 2 gene : 1 gene = 3 : 1
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Pseudogene ,

- () gene
- 11
, G, A, , ,
- () Embryo York Sac

- () G A globin 2 G A
6
- () fetus gene

- () globin (Low expression) 3%

142 146
globin chain 2 chromosome 16 ( gene cluster)
globin chain 2 Chromosome 11 ( gene cluster)

Hb Gower I (22)
Hb Gower II (22)
Hb Portland (22)
Hb F (22)
Hb A (22)
Hb A2 (22)

Embryo
present
present
few
few
-

Fetus-Newborn
0
0
few
60-80%
40-20%
2%

Infant (over 1 year) - Adult

0
0
1%
96-98%
1-3%

:
1. embryonic hemoglobin (Hb Gower I, Hb Gower II, Hb Portland)
8 fetal hemoglobin ( Hb F)
30-35 globin 3-4%
2. Hb F Hb F = 50% Hb A = 50%
3. 6 Hb A = 97%, Hb A2 = 2.5% Hb F < 1%

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1. :
globin

abnormal hemoglobin hemoglobin variant

1. Hb Constant Spring : Hb CS globin chain variant= CS 2 point

mutation terminal codon 142 (UAACAA) 2 gene
31

mRNA globin chain
(variant)
(thalassemia) 1-8%
2. Hb E : globin chain variant = 22
26 (GAGAAG) glutamic
lysine 13% (
- 50 %)
2
Thalassemia
2. :
Thalassemia Thalassemia
Thalassemia
Thalassemia :
2 2
thal-1 globin
globin
(point mutation) 2 1 gene
thalassemia thal-2
Thalassemia :
2 + Thalassemia globin
Thalassemia globin
-thalassemia
(point mutation)
(small deletion) (inser-tion)

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Hemoglobin Typing:
Autosomal recessive
(Trait, Heterozygote)
(Allelic gene) 2 thalassemia abnormal hemoglobin
CS

Thalassemia : 4 () Hb Barts 4 ()
Hb H Inclusion body 2
(high oxygen affinity)
(hemolysis)
Thalassemia : () Hb F
()
(compen-sation)
abnormal globin E ()
A () Hemoglobin E (Hb E)
globin variant CS 2 2
Hemoglobin Constant spring (Hb CS)

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1. thalassemia disease
thalassemic disease

Genotype

1.1 Hb Bart's Hydrops Fetails :

thal-1/ thal-1

1.2 Hb H desease :

1. thal-1thal-2

2. thal-1/HbCS

3.thal-1/Hb Suan Dok

4. thal-1/Hb Q (Mahidol)
1.3 AE Bart's disease:
Double Heterozygote
Hb H disease

1.4 EF Bart's disease :

Hb H

1.5 Homozygous Hb CS :
Basophilic stipping

Hemoglobin Typing
Hb Bart's 90-100%
Hb Portland 10-20%
Cord blood : F, A, Bart's (20 -30%)
: - Hb Bart's (20 - 25%)
- F, A, H ( Bart's)
> 2 Hb F Hb Bart

: - Hb Bart's (25 - 30%)

- F, A, H, CS
:
- A, H, CS
A, H, Suan Dok
A, H, Q

1. thal-1/thal-2

- E = 15%
- A = 75%
- Bart = 5%
( HbF 2%, HbH 3%)
- E + CS =15%
2. thal-1/Hb CS
- A = 75%

- Bart = 5%
(HbF + HbH 5-6%)
1. HbH + Homozygous Hb E - E, F, Bart's E, F, Bart's, HbCS
* A + H F *
CS HbH

2. HbH + thal/HbE
thal-1/HbCS CS
HbCS/Hb CS
- A, A2 Bart's ( Bart 9-12%)
- CS = 5%

2. thalassemia Minor :
Hb Bart's
1. thal-2/ thal-2 Hb Bart's : 10%
2. thal-2/Hb CS Hb Bart's : 10%
3. thalassemia trait :

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1. Hb Bart's Cord Blood
2. Southern blot hybridization
PCR (Polymerase chain reaction)
3. Hypotonic solution (Osmotic
fragility test) 0.36% saline 2
60%
Hb Bart's Cord blood
1. thal-1 trait : 4 7%
2. thal-2 trait : 4%
3. Hb CS trait : 4%
RBC indices thal-1 MCV < 80 fl thal-2 Hb C
MCV
3. thalassemia Disease :
thalassemia Disease :
3.1) thalassemia mjor
3.2) thalassemia /HbE
3.3) thalassemia / Hb Lepore
3.4) thalassemia/
thalassemia

Genotype

Hemoglobin Typing

1.
1.Hb E
2. Hb E
Rare Condition
1.thal.
2. thal.

100%
F, E, A2 & E = 60% *
F, E, A, A2 & E = 50% *
F
F

4. thalassemia minor:
thalassemia Minor : Genotype
4.1) thalassemia trait
1.
2.

4.2) Homozygous Hb E

3.

Hemoglobin Typing
- A, A2 A2 > 3.5%
- MCV < 70 fl
- Osmotic fragility thal-1
- DNA

E, A, A2 E 25 30%
E F A2 E* = 80-90% F 10-20%
*:Electrophoresis Hemoglobin E A2

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5. thalassemia intermedia :
- thalassemia / Hb E
- thalassemia / HPFH (Heriditary Persistent of Fetal Homoglobin)
- thalassemia / thalassemia
- thalassemia / thalassemia
- thalassemia / triplication
Hb Typing :
1. (Iron deficiency anemia)

MCV (trait) thal-1, thal trait

Hb E 13% - 20%
thal-1 Hb E trait Hb E (30%)
OF (Osmotic fragility) trait Hb
Hct

2. Thalassemia Hb typing Hb, Hct,
(MCV), Inclusion body ( HbH disease)
smear Hb typing
family study
3. Osmotic fragility thal-1
thal thal-2 Hb E 50-60%
OF MCV
Hb E DCIP Hb E
microcolumn

()

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1. (Lethal form) Hb Barts hydrops fetalis homozygous

-thalassemia

(pre-eclampsia)
(postpartum hemarrhage)

2. (Severe form) 2
/ Hb < 7 / (./.) Hct < 20%
-
thalassemia major HbE/ thalassemia

3. (Moderate form)
HbE/thalassemia Hb H disease

4. (Mild form) Hb > 9 ./. (Hct > 27%)

Hb E/thalassemia , Hb H disease (deletional
type ), Hb A-E- Bart s disease Homozygous Hb CS

5. (Asymptomatic)

-
- Homozygous thal-2
- Homozygous Hb E

1.
5

(Pneumococcal vaccine ) B
(Hemophilus influenza type B)

-
2.

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3.

2
3.1. Occasional transfusion
Hb < 7 ./. (Hct <20%)
(base-line- level) 20%

3.2. Regular (high) transfusion

2-4 12-15 ./.
(Hb) 11-12 ./.
extramedullary erythropoiesis




200 . 1 (unit)

leucocyte depleted PRC 12-15 ././

5 Hepatitis B, C, HIV antibody, HIV
antigen, syphilis
4.
(iron overload) 1
1.16 . ineffective erythropoiesis

(serum ferritin) serum
ferritin 2,500 /(./.) 15 / (
)
(serum ferritin) 1,000 ./.
hypertransfusion 1 15
serum ferritin
- 30 Deferrioxamine (DesferalR) 20-40 ././
(subcutaneous route)
(Infusion pump) 10-12
serum ferritin 3-6 regular (high) transfusion

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5. -
hypersplenism

5.1 6 .
5.2 250 . /./
5
(encapsulated bacteria)
Pneumococcal Hemophilus influenza vaccine 2 1
Penicillin V 125 250 . 2

6. (Stem Cell Transp-lantation : SCT)

( HLA : human leucocyte antigen)
75-80


1. ( thal major severe HbE/thalassemia)
2. Hb (>10g/dl)
erythropoiesis

3. serum ferritin
3,000 ./.
4.
portal fibrosis
5. HLA
HLA 25%
6.

-
-
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[ 4 ]

1. Coa A, Gabutti V, Galanello R, Masera G, Modell B, Plama A, et al. Management protocol for
the treatment of thalassemia patients. 1997 ed. Nicisia, Cyprus: Thalassemia Internation
Federation; 1997.
2. Miller DR. Blood diseases of Infancy and Childhood. 7th ed. St. Louis, U.S.A.: Mosby Yearbook
Inc; 1995.
3. Modell B, Berdoukas V. Growth puberty and endocrinopathy. In: The Clinical Approach to
Thalassemia. London: Grune & Stratton; 1981. p. 175-97.
4. Nathan DG. Hematology of Infancy and Childhood. 4th ed. U.S.A: W.B. Saunders company; 1992.
5. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood
1997;89(3):739-61.
6. Rebulla P, Modell B. Transfusion requirements and effects in patients with thalassaemia major.
Cooleycare Programme. Lancet 1991;337(8736):277-80.
7. Tanphaichitr VS, Suvatte V, Mahasandana C, Tuchinda S. Hypertension posttransfusion in Thai
thalassemic children: early detection and management. Birth Defects Orig Artic Ser
1988;23(5B):251-5.
8. Weatherall DJ, Clegg JB, editors. The Thassaemia Syndromes. 4th ed. Oxford, United Kingdom:
Blackwell Science; 2001.

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