Thalassemia

OUTLINE

ThalassemiaEtiologyDiagnosisSigns & Symtoms Treatment - folic --(iron chelating)-

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

Definition

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.

2

1. (heterozygote, trait) Hb typing

alpha chain gene 4

1. Alpha Thalassemia

Hydrops fetalis :

Hb H disease : Hb Heinz body hemolytic, microcyticanemia splenomegaly

-thal minor : mild microcytic anemia iron deficiency

Carrier :

1. gene 1

2. gene 2

3. gene 3

4. gene 4

1. Alpha Thalassemia

Beta chain gene 2

Normal

-thalassemiaminor or trait

-thalassemiamajor or Cooleys anmia

1

2 severe microcytic anemia, hypochromic anemia

1. Beta Thalassemia

(baseline

Hb/Hct)

(most severe)

Hb Barts hydropsfetalis

(severe)

2 ()

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

-thal/ -thal () -thal/HbE disease ()

(baseline Hb/Hct)

(moderate)

Hb > 7 9 g/dL(Hct >20 27 %)

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

(mild)

Hb 9 g/dl (Hct 27 %)

-thal/ Hb E , Hb H disease , Hb A-E-Barts disease, Homozygous Hb CS

(Asymptom-atic)

Hb (low normal)

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

Test Age 18-49

Hemoglobin (g/dL) M 13.517.5

F 12.016.0

Hematocrit (%) M 4153

F 3646

MCV (fL) 80100

MCHC (%) 3137

MCH (pg) 2634

Serum iron (mcg/dL) M 50160

F 40150

Reference Range

Test Age 1849

TIBC (mcg/dL) 250400

RDW (%) 1116

Ferritin (ng/mL) M 15200

F 12150

Folate (ng/mL) 1.816.0a

Vitamin B12 (pg/mL) 100900a

Erythropoietin (mU/mL) 019F, 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

/

labIron deficiency anemia(IDA) VS Thalassemia

Parameter IDA Thalassemia

Hb

Hct

MCV

MCHC

TIBC

Serum ferritin

Serum Iron

(Hemoglobin analysis) high performance liquid chromatography (HPLC), low -pressure liquid chromatography (LPLC), hemoglobin electrophoresis 3

(definite diagnosis)

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)

Iron chelation 2 injection oral tablet

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

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

4.1 injection (1st line )

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

Administration : scMechanism of action : Storage : room temp 25 C , reconstitute room temp 24 hr ,

complication dose

4.2 Oral tablet (2nd line)

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)

Desferasirox(tridentate)

Deferiprone(bidentate)

Desferrasioxamine Deferiprone DeferasiroxMolecular weight 560 139 373Chelator: iron 1:1 (hexandentate) 3:1 (bidentate) 2:1 (tridentate)Route of administration

Subcutaneous or intravenous

Oral tablets or liquid Oral suspension

Iron excretion Urine, fecal Urine FecalPlasma half-life 20 min 1-3 h 8-16 hUsual dose 40 mg/kg/d 75-100 mg/kg/d 20-40 mg/kg/dMain side effects Local reactions, auditory,

retina, allergy, bone abnormalities, Yersinia

infection

Gastrointestinal, neutropenia/ agranulocytosis, arthralgia, liver

enzyme rise, zinc deficiency

Gastrointestinal, rash, renal, liver

Advantages 36 years of experience Best for cardiac iron removal Once-daily administration

Disadvantages Mode of administration, lack of compliance

Weekly blood count monitoring in first year

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 gland3. Heart complications arythmia, systolic dysfunction, pleural effusion, heart failure 4. Liver complications hepatitis, enlarged liver, cirrhosis5. Bone complications skeletal deformities, bone and joint pain, and osteoporosis

5 (Folate)

6

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 mgAneurine HCl 2 mgPyridoxine 0.5 mgCyanocobalamin 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 sex-linked recessive

3. Hemophlia C factor XI 1% Hemophilia autosomal recessive

3

Factor VIII Factor IX

5-49%

1-5%

1%

Hemophilia A Hemophilia B Hemophilia C

1.

VIII IX XI

2.

sex-linked recessive sex-linked recessive Autosomal recessive

3.

4. 85 % 15 % < 1 %

5.

6.

7. Hemostatic level 25 % 25 % 15 %

8. Biological half -life 12 - 18 30 2 - 3

9.

8-12 24 1-2

10. FFP, cryoprecipitate FFP FFP

FVIII concentrate FIX concentrate Cryoremoved