Thalassemia

OUTLINE
Thalassemia
Etiology
Diagnosis
Signs & Symtoms

Treatment
- folic
-
-(iron chelating)
-

Definition
(thalassemia syndromes)

(thalassemia) /
(hemoglobinopathy)
(hemolytic anemia)

autosomal




Thalassemic facies


- 90% hemoglobin
- Hemoglobin 4

Hemoglobin
- 96% HbA(22) alpha 2 beta 2
- 3% HbA2(22) alpha 2 delta 2
- 1% fatal Hb (HbF,22) alpha 2 gamma 2

 2
1.
(heterozygote, trait)
Hb typing


2.

1. Alpha Thalassemia
alpha chain gene 4

1. Alpha Thalassemia
1. gene 1
Carrier :
2. gene 2
-thal minor :

mild microcytic anemia iron deficiency

3. gene 3
Hb H disease : Hb Heinz body hemolytic, microcytic
anemia splenomegaly

4. gene 4
Hydrops fetalis :

1. Beta Thalassemia
Beta chain gene 2

Normal
-thalassemia
minor or trait
-thalassemia
major or Cooleys
anmia

2
severe microcytic anemia,
hypochromic anemia

(most severe)

(severe)

(baseline
Hb/Hct)

Hb Barts hydrops
fetalis

Hb < 7 g/dL
2
(Hct < 20 %)
()

-thal/ -thal (
) -thal/Hb
E disease ()

(baseline Hb/Hct)

Hb > 7 9 g/dL
-thal/ -thal ()
(moderate)
(Hct >20 27 %)
-thal/ Hb E ()
Hb H disease ()

Hb 9 g/dl (Hct 27 -thal/ Hb E ,
(mild)
%)
Hb H disease ,
Hb A-E-Barts disease,
Homozygous Hb CS

Hb (low normal)
(Asymptom

atic)
Homozygous -thal2,
Homozygous Hb E

Differential Diagnosis

-


- (complete blood count, CBC)
(red cell indices) (morphology)
(hypochromia) (microcytic)
(poikilocytosis) MCV MCH
- inclusion body
Hb H

 (mean) -2 SD Hemoglobin (Hb), Hematocrit (Hct)

Mean Corpuscular Volume (MCV)

Reference
Range

Reference
Range

Test

Age 18-49

Test

Hemoglobin (g/dL)

M 13.517.5

TIBC (mcg/dL)

F 12.016.0

RDW (%)

Hematocrit (%)

M 4153

Ferritin (ng/mL)

F 3646

Age 1849
250400
1116
M 15200
F 12150

MCV (fL)

80100

Folate (ng/mL)

1.816.0a

MCHC (%)

3137

Vitamin B12 (pg/mL)

100900a

MCH (pg)

2634

Erythropoietin (mU/mL)

Serum iron (mcg/dL)

M 50160
F 40150

019

F, female; M, male; MCH, mean corpuscular hemoglobin; MCHC, mean

corpuscular hemoglobin concentration; MCV, mean corpuscular
volume; RBC, red blood cell; RDW, red blood cell distribution; TIBC,
total iron-binding capacity. aVaries by assay method.

Differential Diagnosis

Hb typing

 lab
- Hb
- Hct

- MCV
-MCHC
- Serum Iron

- Serum ferritin
/
- TIBC

 lab
Iron deficiency anemia(IDA) VS Thalassemia
Parameter
Hb
Hct
MCV
MCHC
TIBC
Serum ferritin
Serum Iron

IDA

Thalassemia

 (definite diagnosis)
(Hemoglobin
analysis) high performance liquid
chromatography (HPLC), low -pressure liquid chromatography (LPLC),
hemoglobin electrophoresis

3


Thalassemia

 1 ( )

 2
( 1 1 )

-

50 1 2
-

50 1 2
-

 3
( 1 1 )

100
-

 4 ( )

25 1 4
-

( )
50 2 4
-

25 1 4

 5 ( 1 1 )

50 1 2
-

50 1 2



(phenotypic diagnosis)
mutation gene mutation
gene copy mutation

1.

- 5

-
-

2. folic acid

- > 1 1 (5 )
- < 1 1/2
(high transfusion)

Folic acid

: Vitamin B9
: 5 mg/tab (film-coated)
: NDD ( mims)
Storage : ,
Metabolism :
Excretion : ( )
folic acid :


, , ,
, ,

3. Transfusion
- Hb Goal post transfusion = 10 g/dL
- Need approximately every 4 weeks
PRC 12-15 mL/kg
2
hypertension, convulsion cerebral hemorrhage (HCC syndrome)

2
diuretic antihypertensive drugs
HCC syndrome 5

4. (Iron chelation)

1. (high transfusion) 1
2. (PRC) 15
3. (serum ferritin) 1,000 ng/mL 2 3

Iron chelation 2 injection oral tablet

4.1 injection (1st line )

Desferrioxamine (Desferal) 20-40 mg/kg/ 5 7
/
(infusion pump) 8-12
serum ferritin 6

- 3
- SE: ototoxicity with high frequency hearing loss, retinal changes, bone
dysplasia
-

monitor

Administration : sc
Mechanism of action :


Storage : room temp 25 C , reconstitute room
temp 24 hr ,

4.2 Oral tablet (2nd line)

complication
dose

2 Deferiprone (L1) Deferasirox

1. Deferiprone (L1, GPO-L-ONE)
Desferrioxamine 50-75 mg/kg/
2-3 agranulocytosis, hepatic transminitis, arthropathy
CBC 1-2 2

2. Deferasirox

2 20-30 ./.

Desferrioxamine
(hexadentate)

Deferiprone
(bidentate)

Desferasirox
(tridentate)

Desferrasioxamine
Deferiprone
Molecular weight
560
139
Chelator: iron
1:1 (hexandentate)
3:1 (bidentate)
Route of
Subcutaneous or
Oral tablets or liquid
administration
intravenous
Iron excretion
Urine, fecal
Urine
Plasma half-life
20 min
1-3 h
Usual dose
40 mg/kg/d
75-100 mg/kg/d
Main side effects Local reactions, auditory, Gastrointestinal, neutropenia/
retina, allergy, bone agranulocytosis, arthralgia, liver
abnormalities, Yersinia
enzyme rise, zinc deficiency
infection
Advantages
36 years of experience Best for cardiac iron removal
Disadvantages

Mode of administration, Weekly blood count monitoring

lack of compliance
in first year

Deferasirox
373
2:1 (tridentate)
Oral suspension
Fecal
8-16 h
20-40 mg/kg/d
Gastrointestinal,
rash, renal, liver

Once-daily
administration
Cost

5. (Splenectomy)

hypersplenism

6 .
250 mL/kg/
hypersplenism




5

Pneumococcal vaccine
1
aspirin 2 4 / > 800x109/L

penicillin (250 ) 1 2
0.5

6. (stem cell transplantation: SCT)

1.
2. HLA
HLA 1
4
1 10,000 1 100,000
3.
500,000 1,5000,000

Complications of thalassemia
1. Enlarged spleen (hypersplenism)
2. Hormone complications delayed
puberty, retricted growth, overactive
thyroid gland
3. Heart complications arythmia,
systolic dysfunction, pleural effusion, heart
failure
4. Liver complications hepatitis,
enlarged liver, cirrhosis
5. Bone complications skeletal
deformities, bone and joint pain,
and osteoporosis








5
(Folate)


1.

.

.

.

.

(thalassemia syndromes)
(thalassemia)
(hemoglobinopathy)
(hemolytic anemia)

.
G6PD
.
sickle cell anemia
.
.

2. Folic acid
15
Folic acid
.
.
.
.
.

 . NDD Folic 5 mg
Folic acid 200 mcg

3. Folic acid

.
.
.
.
.

 .
folic acid :


, , ,
, ,

4.
Hemovit

.

.
. drug interaction

.
Haemo-vit 1
Dried Ferrous sulfate
135
mg
Aneurine HCl
2
mg
Pyridoxine
0.5
mg
Cyanocobalamin
5
mcg
. 1
Ferrous Sulfate Equivalent to Iron 60 mg. 4 10

.

.

. drug
interaction

Hemophilia

1. Hemophilia A factor VIII clotting activity (F VIII:C)

85% hemophilia
sex-linked recessive
2. Hemophlia B (Christmas Disease) factor IX
10 15% Hemophilia sexlinked recessive
3. Hemophlia C factor XI 1%
Hemophilia autosomal recessive

Factor VIII Factor

IX
5-49%

1-5%

1%

Hemophilia A

Hemophilia B

Hemophilia C

1.

VIII

IX

XI

2.

3.
4.
5.
6.
7. Hemostatic level
8. Biological half -life
9.

10.

sex-linked recessive

sex-linked recessive

Autosomal recessive

85 %

25 %
12 - 18
8-12

15 %

25 %
30
24

<1%

15 %
2 - 3
1-2

FFP, cryoprecipitate
FVIII concentrate

FFP
FIX concentrate

FFP
Cryoremoved