Thalassemia in Adult

Savita Handayani
Internal Medicine Department
Hematology Oncology Division
Haji Adam Malik Hospital/Universitas Sumatera Utara Hospital
Faculty of Medicine Universitas Sumatera Utara
Thalassemia Red blood cell abnormalities result in
reduction or absence globin chain
formation -> heredity based on
Mendel's Law

Hukum
THALASSEMIA

• The reduction or abscence-production

Thalassemia of the globin chain determines the
genotype

• “abnorma hemoglobin”
Hemoglobinophaty • Different structure and characteristic
• HbS, HbC, HbE, HbD, Hb Lepore
Type of Hemoglobin

Hemoglobin Type Globin Chains

• Hgb A—92%--------- a2b2

a2d2
• Hgb A2—2.5%--------
a2g2
• Hgb F — <1%---------
b4
• Hgb H ------------------
g4
• Bart’s Hgb-------------- a2b26 gluval
• Hgb S-------------------- a2b26 glulys
• Hgb C-------------------
 Classification of Thalassemia
Alpha Thalassemia
1 Deletion—Silent carrier; not clinically significant
2 Deletion—a Thalassemia trait; mild anemia,
hypochrome microcytic
3 Deletion—HbH; varies severity, milder than beta
major thalassemia
4 Deletion—Bart’s Hb; Hydrops Fetalis;
Incompatible with life.

Beta Thalassemia Severity

• Thalassemia Minor
Hundreds of types of mutations that might
occur, the genotype and phenotype are more • Thalassemia
varies. Intermediate
• Thalassemia Major or
Cooley's Anemia
Spectrum of Thalassemia Syndrome

Viprakasit V,et al. Guidelines for the management of transfusion dependent

thalassemia (TDT). 3rd edition. Thalassaemia International Federation. 2014: 14-
25
Laboratorium
• Primary hematological test
• Hb Electrophoresis
• Molecular analysis

Brancaleoni V, et al. Int. Jnl. Lab. Hem. 2016, 38 (Suppl. 1), 32-40
Primary hematological test

• Alpha or beta • Peripheral blood

thalassemia carrier morphology:
can present with • Microcytic hypochrome,
anemia or without anisocytosis,
anemia poicylocytosis, target
cells, normoblast
• CBC: depletion of Hb
• Iron status:
• MCV, low MCH • Serum ferritin
• Transferin saturation

Brancaleoni V, et al. Int. Jnl. Lab. Hem. 2016, 38 (Suppl. 1), 32-40
 Apus darah
Screening Hb ↓ CBC: tepi
Indeks reti-
MCV- MCH kulosit

Microcytic, Normocytic, Macrocytic

hypochromic normochromic
MCV > 95 fL
MCV < 80 fL MCV 80-95 fL
MCH < 27 pg MCH ≥ 27 pg
Megaloblastic: vitamin
Iron deficiency anemia Hemolytic anemia
B12 or folate
Thalassemia Anemia due to chronic
deficiency
Anemia due to chronic disease
Non-megaloblastic:
disease Anemia due to bleeding
alcohol, liver disease,
Lead poisoning Kidney illness
myelodysplastic
Sideroblastic anemia Mixed deficiency
syndrome,
Bone marrow failure
aplastic anemia
Mentzer Index

Mentzer index = MCV / RBC count

Indeks <13 suggestive thalassemia

Indeks >13 suggestive of iron deficiency

• Usually used to differentiate iron deficiency anemia with

thalassemia but has a wide variety of results

Am Fam Physician. 2010;81(12):1462-1471

Differential Diagnosis of Hypochrome Microcytic Anemia

___________________________________________________________
Laboratory testing Iron deficiency Thalassemia Minor Chronic disease
___________________________________________________________

MCV ↓ ↓ N/↓
Serum Iron ↓ N ↓
TIBC ↑ N ↓
Transferin Saturation ↓ N N/↓
Feritin ↓ N ↑
___________________________________________________________
Electrophoresis Hb in Normal
People
Elektrophoresis in Beta Thalassemia trait
Electrophoresis Hb in Beta thalassemia major
Electrophoresis Hb in Hb E trait
Electrophoresis Hb inHb E
Molecular Analysis
• Genotype test = DNA test
• Examine the DNA sequences that encode globin
chains or the loss of genes
• To ensure patients suspected of thalassemia
clinically and in prenatal and neonatal screening
tests
Viprakasit V,et al. Guidelines for the management of transfusion dependent thalassemia (TDT). 3rd edition.
Thalassaemia International Federation. 2014: 14-25
 Until now, thalassemia can
Major Treatment not be cured

Initial transfusion: Further transfusion:

Hb < 7 g/dL
(2 sequential test in 2
weeks)

Hb ≥ 7 g/dL
Hb ≤ 9-10 g/dL Blood transfusion*
with: Blood
Especially (target Hb 11-12
•Facies Cooley transfu
• Bone fracture children g/dL)
sion*
•Suspect extramedular
hematopoesis mass ,
a.l: mediastinum * When available, blood is given in the form of low leukocyte (Leucodepleted) P
screening
Specific condition:

Hb ≥ 7 g/dL
With infection, but WITHOUT: Blood transfusion *
Hb < 7
Face changes g/dL
Bone fracture Treat the
infection Postpone
Extra medular hematopoesis Hb ≥ 7
(max 2 transfusion 
g/dL
weeks) observed

# Pada Thalassemia β-HbE atau penyakit HbH

• Out of 73,898 samples, 1104 samples (1.49%) were reactive by NAT. out of these 1104 samples,
73 were reactive for HIV-1 (0.09%), 186 were reactive for HCV only (0.25%), 779 (1.05%) were
reactive for HBV only, and around 66 (0.08%) were HBV-HCV co-infections. There was one HIV,
37 HCV, 73 HBV and 10 HBV-HCV co-infection cases that were not detected by serology but
reactive on NAT testing, with a combined yield of 1 in 610 donations (total 121 NAT yields).
• CONCLUSION:
• NAT could detect HIV, HBV and HCV cases in blood donor samples that were undetected by
serological tests. NAT can interdict a large number of infected unit transfusions and thus help in
providing safe blood to the patients.

Transfus Apher Sci.

 …Treatment
2. Excessive iron removal
• Method
Injections: Under the skin of
Deferioxamine /
Desferal®
 Oral:
Deferiprone/Ferriprox®
Deferasirox/Exjade®

If iron chelation therapy is not optimal, iron buildup

occurs in all organs, especially in the liver, heart, and
hormonal glands
Organ Systems Affected by Iron Overload

Pituitary
gland • Iron overload results in nontransferrin-
bound iron in the plasma
Heart • Increased iron uptake into selective organs
• Generation of free hydroxyl radicals
Liver
Pancreas
Gonadal

Tissue damage

Haematologica. 2013;
98(6)
 Test
• Blood glucose
• Calcium, phosphate
• Cholesterol, HDL, LDL, trigylceride
• Echocardiography (FS, FE, La/Ao ratio, end
diastolic diameter)
• MRI T2* heart & liver (if possible)
• Spirometry
• Bone age
• Puberty
• FSH, LH, testosteron and/orestradiol
• FT4, TSH
• Radiology (vertebra, femur, humerus, hip)#
• US abdominal#
• CT scan #
# If possible
 Survival of Thalassemia

100
1.00

0.75
75
Survival probability

Birth cohort

Survival (%)
1985–97
1980–84
0.50 1975–79 50
1970–74
1965–69 Well-chelated patients
1960–64
0.25 Poorly chelated patients
(P<0.00005) 25

0
0 5 10 15 20 25 30
0
Age (years) 10 15 20 25
Age (years)

Borgna-Pignatti C et al. Haematologica 2004;89:1187–1193.

 Haji Adam Malik Hospital
(Inpatience)
Kunjung
an
Dewasa

Pasien
Dewasa Jan - Jul
2018
2017
Total
kunjung 2016
an
Total
Pasien
Total Pasien

0 100 200 300 400 500 600 700 800 900

 Haji Adam Malik Hospital
(Inpatience)
Kunjung
an
Dewasa

Pasien
Dewasa Jan - Jul 2018
2017
2016
Total
kunjung
an
Total Total Pasien
Pasien

0 100 200 300 400 500 600 700 800 900