Download - Update on Thalassaemia Kk Maran
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UPDATE ON THALASSAEMIAUPDATE ON THALASSAEMIA
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Epidemiology of thalassemia
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THALASSAEMIATHALASSAEMIA Di Malaysia
Pembawa thalassaemia (Thalassaemia minor/trait) 600,000 – 1 juta orang 5% daripada populasi penduduk
Thalassaemia Major 2500 pesakit
Melayu, Cina & Bumiputera Sabah & Sarawak
Di Malaysia Pembawa thalassaemia (Thalassaemia minor/trait)
600,000 – 1 juta orang 5% daripada populasi penduduk
Thalassaemia Major 2500 pesakit
Melayu, Cina & Bumiputera Sabah & Sarawak
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ObjectivesObjectivesObjectivesObjectives
1.1. To promote awareness on β-thalassemia To promote awareness on β-thalassemia disease & carrier statusdisease & carrier status
2.2. To provide population screening on To provide population screening on voluntary basis for those age 16 years & voluntary basis for those age 16 years & aboveabove
3.3. To provide counseling for all those To provide counseling for all those confirmed as β-thalassemia carriersconfirmed as β-thalassemia carriers
1.1. To promote awareness on β-thalassemia To promote awareness on β-thalassemia disease & carrier statusdisease & carrier status
2.2. To provide population screening on To provide population screening on voluntary basis for those age 16 years & voluntary basis for those age 16 years & aboveabove
3.3. To provide counseling for all those To provide counseling for all those confirmed as β-thalassemia carriersconfirmed as β-thalassemia carriers
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WHAT IS THALASSEMIA ?WHAT IS THALASSEMIA ?
Inherited disease of blood that reduces the amount of haemoglobin body can make and so can cause anaemia.
Inherited disease of blood that reduces the amount of haemoglobin body can make and so can cause anaemia.
GENETIC DISEASE
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What is Haemoglobin (Hb)?What is Haemoglobin (Hb)?
Blood vessel
Platelet White blood cell Red blood cell
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The hemoglobin moleculeThe hemoglobin molecule
Resides in RBCs, responsible for carrying and transporting O2
Is a tetramer, consist of four polypeptide groups, 2 α and 2 β chains (α2β2)
Up to 4 O2 molecules can bind to the 4 heme groups.
Resides in RBCs, responsible for carrying and transporting O2
Is a tetramer, consist of four polypeptide groups, 2 α and 2 β chains (α2β2)
Up to 4 O2 molecules can bind to the 4 heme groups.
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Haemoglobin MoleculeHaemoglobin Molecule
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Genes for HaemoglobinGenes for Haemoglobin
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BETA THALASSEMIA Lack of beta chain
BETA THALASSEMIA Lack of beta chain
Most of thalassemia result from point mutation within or close to the globin gene complex.
Each mutation result in reduction or abolition of globin chain function.
Most of thalassemia result from point mutation within or close to the globin gene complex.
Each mutation result in reduction or abolition of globin chain function.
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BETA THALASSEMIA
CLINICAL SYNDROMEo Thalassemia Minor or Thalassemia Trait (ß+/ßa) or
(ßo/ßa) o Thalassemia Intermedia (ß+/ß+) or (ß+/ßo)o Thalassemia Major or Cooley's Anemia (ßo/ßo)
BETA THALASSEMIA
CLINICAL SYNDROMEo Thalassemia Minor or Thalassemia Trait (ß+/ßa) or
(ßo/ßa) o Thalassemia Intermedia (ß+/ß+) or (ß+/ßo)o Thalassemia Major or Cooley's Anemia (ßo/ßo)
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Beta ThalassaemiaBeta Thalassaemia
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Beta Thalassaemia Trait (Minor)Beta Thalassaemia Trait (Minor)
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Beta Thalassaemia MajorBeta Thalassaemia Major
Both parents thalassaemia major = 100% fetal thalassaemia major.
1 parent thalassaemia major + 1 parent thalassaemia trait = 50% thalassaemia major, 50% thalassaemia trait
1 parent thalassaemia major + 1 normal parent = 100% thalassaemia trait
Both parents thalassaemia major = 100% fetal thalassaemia major.
1 parent thalassaemia major + 1 parent thalassaemia trait = 50% thalassaemia major, 50% thalassaemia trait
1 parent thalassaemia major + 1 normal parent = 100% thalassaemia trait
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ALPHA THALASSEMIAALPHA THALASSEMIA
Lack of Alpha Chain More than 95% of thal are
due to deletion of one or both of the tandem globin genes located on chromosome 16.
Lack of Alpha Chain More than 95% of thal are
due to deletion of one or both of the tandem globin genes located on chromosome 16.
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Alpha ThalassaemiaAlpha Thalassaemia
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Alpha ThalassaemiaAlpha Thalassaemia
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ALPHA THALASSEMIAALPHA THALASSEMIA
5 possible genotypes:5 possible genotypes:
Type Genotype
Normal /
+ heterozygote -/
+homozygote -/-
o heterozygote --/
ohomozygote --/--
o +double hetero --/-
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LAB INVESTIGATIONSLAB INVESTIGATIONS
Screening Test
1. Full Blood Count2. Full Blood Picture3. Reticulocyte count.4. S. Iron/TIBC, S. Ferritin
Screening Test
1. Full Blood Count2. Full Blood Picture3. Reticulocyte count.4. S. Iron/TIBC, S. Ferritin
Diagnostic Test
1. Hb Analysis
Confirmatory Test 1. DNA Analysis
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INVESTIGATIONSFBC
INVESTIGATIONSFBC
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INVESTIGATIONSFBP - smear
INVESTIGATIONSFBP - smear
Immune haemolytic A
Thalassemia trait Thalassemia major
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INVESTIGATIONSReticulocytes count
INVESTIGATIONSReticulocytes count
Reticulocytes
- are juvenile red cells.
- Number of reticulocytes in periperal blood is a fairly accurate reflection of erythropoietic activity.
Range of retic count in health =
50-100x109/l
(0.5 – 2.5%)
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INVESTIGATIONSHb Analysis
INVESTIGATIONSHb Analysis
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THALASSEMIA SYNDROMES THALASSEMIA SYNDROMES
SEA α0 α-thal 2 , 3.7 del
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Molecular diagnosis Molecular diagnosis
Methods are based on the polymerase chain reaction. dot blot analysis, reverse dot blot analysis, the amplification refractory mutation system (ARMS), denaturing gradient gel electrophoresis, mutagenically separated PCR, gap-PCR and Restriction endonuclease analysis.
Methods are based on the polymerase chain reaction. dot blot analysis, reverse dot blot analysis, the amplification refractory mutation system (ARMS), denaturing gradient gel electrophoresis, mutagenically separated PCR, gap-PCR and Restriction endonuclease analysis.
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Confirmatory DiagnosisConfirmatory Diagnosis Currently molecular diagnosis available in Malaysia at:
1. IMR2. HUKM3. UMMC4. Some private labs outsource to Singapore or
Australia5. HKL to commence next year
Currently molecular diagnosis available in Malaysia at:
1. IMR2. HUKM3. UMMC4. Some private labs outsource to Singapore or
Australia5. HKL to commence next year
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Management of Thalassaemia Intermedia/Major
Management of Thalassaemia Intermedia/Major
Transfusions Should be avoided Indicated if situations of poor growth or abnormal facies
Splenectomy In the presence of hypersplenism or decline in Hb levels
Iron chelation When ferritin exceeds 1000 micrograms/L Less frequent than the thalassaemia major patients
Supplements Folate
Transfusions Should be avoided Indicated if situations of poor growth or abnormal facies
Splenectomy In the presence of hypersplenism or decline in Hb levels
Iron chelation When ferritin exceeds 1000 micrograms/L Less frequent than the thalassaemia major patients
Supplements Folate
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SETIAPBULAN
SEPANJANGHAYAT
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Complications of Thalassamia and Treatment
Complications of Thalassamia and Treatment
Acute febrile illness Complications due to iron overload
Cardiac complications Endocrine complications – DM, hypothyrodism, delayed puberty,
short stature Skin Other organs
Complications from excessive erythropoiesis Challenge on the facial appearance Osteoporosis and osteopenia
Transfusion related complications – Hep B/C/ HIV Psychosocial problems
Lack of self-esteem, lack of confidence, adjustment, etc. Poor academic results (due to absence) Discrimination against employment, relationships, etc.
Acute febrile illness Complications due to iron overload
Cardiac complications Endocrine complications – DM, hypothyrodism, delayed puberty,
short stature Skin Other organs
Complications from excessive erythropoiesis Challenge on the facial appearance Osteoporosis and osteopenia
Transfusion related complications – Hep B/C/ HIV Psychosocial problems
Lack of self-esteem, lack of confidence, adjustment, etc. Poor academic results (due to absence) Discrimination against employment, relationships, etc.
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Treatment – Iron chelation
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Giving DesferrioxamineGiving Desferrioxamine
Peralatan Membancuh ubat Ubat dalam syringe
Cucuk bawah kulit Tampal plaster Mesin dalam sarung
(Sarawak Thalassaemia Association)
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Haematopoietic cell transplant (BMT)Haematopoietic cell transplant (BMT)
The only curative option A form of gene therapy Replace defective haematopoietic system from
compatible donors Acute mortality rate Chronic morbidity Must be offered to all transfusion dependent patients
as early as possible
The only curative option A form of gene therapy Replace defective haematopoietic system from
compatible donors Acute mortality rate Chronic morbidity Must be offered to all transfusion dependent patients
as early as possible
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CURE vs
DEATH
CURE vs
DEATH
CUREClass 1: 91 %Class 2: 83 %Class 3: 58 %Adults : 62 %
DEATHClass 1 7%Class 2 13%Class 3 21%Adults 34%
? ?? ?
?
?? ?
??
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Algorithm Algorithm PerkhidmatPerkhidmatanan
FBC
HPLC
Βeta-Thalassaemia Carrier Voluntary Screening
Walk-in for voluntary screening (KK/KPL)
Register – “Thalassaemia Screening” (PER-PL102)
2Check & treat for Iron Deficiency
Anaemia
Within normal limit; alpha-thalassaemia cannot be excluded
RESPONSIBILITY
Pembantu Tadbir Pembantu Rendah Am
(PRA) Pembantu Perawatan
Kesihatan (PPK)
1Post-test counseling
aHb↓ MCH <27
aHb – normal MCH >27
aHb – normal MCH <27
(Keep blood for HPLC)
Counseling & Send blood for
DNA Analysis to IMR
Beta-thalassaemia / Hb E carriers
Counseling & Beta-Thalassaemia Carrier
National Registry
No response
Blood taking
Juruteknologi Makmal Perubatan (JTMP)
Penolong Pegawai Perubatan
Jururawat Terlatih
2Pegawai Perubatan 2Pakar Perubatan Keluarga
Pegawai Perubatan Pakar Perubatan Keluarga
Pakar Perubatan Keluarga Pegawai Perubatan Penolong Pegawai
Perubatan Jururawat Terlatih
Pre-test counseling Penolong Pegawai
Perubatan Jururawat Terlatih
3Register Recall Register
3Penolong Pegawai Perubatan
aReturn for Hb & MCH results
1Penolong Pegawai Perubatan
1Jururawat Terlatih
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Kad Status PembawaKad Status Pembawa
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Prenatal DiagnosisPrenatal Diagnosis
To diagnose whether the fetus has Thalassaemia.
Why do we want to diagnose? If fetus is normal, increased surveillance is not
required. Reassuring to the parent. If fetus is affected, surveillance is increased. ? Termination of pregnancy
To diagnose whether the fetus has Thalassaemia.
Why do we want to diagnose? If fetus is normal, increased surveillance is not
required. Reassuring to the parent. If fetus is affected, surveillance is increased. ? Termination of pregnancy
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Prenatal DiagnosisPrenatal Diagnosis
Chorionic Villus Sampling (CVS) Amniocentesis Fetal Blood Sampling (FBS) Pre-implantation Genetic Diagnosis (PGD)
Chorionic Villus Sampling (CVS) Amniocentesis Fetal Blood Sampling (FBS) Pre-implantation Genetic Diagnosis (PGD)
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Chorionic Villus SamplingChorionic Villus Sampling
Sampling of placental tissue.
10-13 weeks gestation. Transvaginal /
Transabdominal.
Sampling of placental tissue.
10-13 weeks gestation. Transvaginal /
Transabdominal.
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AmniocentesisAmniocentesis
Aspiration of amniotic fluid (15-20ml). 15-16 weeks gestation.
Aspiration of amniotic fluid (15-20ml). 15-16 weeks gestation.
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Fetal Blood SamplingFetal Blood SamplingCan be done during 16-18 weeks of gestation
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Hydrops FetalisHydrops Fetalis
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Thank youThank you