KURIKULUM VITA

Nama : Dr.Max.F.J.Mantik, SpA(K)

Tempat/Tanggal Lahir : Langowan, 14 Juli 1951
Riwayat pekerjaan : - Kepala Sub.Bagian Hematologi-Onkologi
Bagian Ilmu Kesehatan Anak FK Unsrat / RSUP Manado
- KPS IKA FK Unsrat
- Ketua TKP PPDS I FK Unsrat
Riwayat Pendidikan : - SMA Gabungan, 1970, Jayapura
- Dokter, FK Unsrat. 1979
- Dokter Spesialis Anak, FK Unsrat, 1985
- Dokter Spesialis Anak Konsultan, Kolegium Ilmu
Kesehatan Anak Indonesia, 2000
Pendidikan tambahan : - Pediatric Hematology Researcher, Faculty of
Medicine Tokai University, Isehara, Japan, 1992
- Pediatric Oncology, Department of Pediatric
Oncology, Academish Medish Centrum (AMC)
Universiteit van Amsterdam, Netherland, 1996 1997
- Reproductive Medicine and Reproductive Biology, Faculty
of Medicine University of Geneve,Switzerland,1999
- Fellowship in Bleeding Disorder, International Hemophilia
Training Center, Faculty of Medicine, Ramathibodi
Hospital Mahidol University, Bangkok, Thailand, 2003
 Thalasemia

Mantik Max FJ
Div of Hematology-Oncology Dept of Paediatrics
Faculty of Medicine University of Sam Ratulangi /
Prof Dr RD Kandou General Hospital
 Definition
A heterogeous family of inherited disorder
of hemoglobin synthesis
Thalasa is a greek for sea
 Pathophysiology
To understand how globin chain imbalance
causes the characteristic
ineffective erythropoesis
shortened red cell survival
Consist of -thalasemia and -thalasemia
 Structure hemoglobin
Globin portion
Polypeptide chain
Normal adult hemoglobin(HbA) is composed 141

amino acid residues of chain and 146 amino acid

of chain
Heme portion
Iron and porphyrin
 The normal human hemoglobin

Embrionic hemoglobin
Hb Gower 1 2 2
Hb Gower 2 2 2

Hb F 2 2

Hb A 2 2
Hb A2 2 2
 Clasification
Thalasemia trait
Normal performance
Intermediate
Hb range around 10 11 g/dl
Mayor thalasemia
Hb < 8 g/dl
 Hematologic changes
Hb range from 2 8 g/dl
The red cells
Hypochromia
Variation in size and shape
Fragmentosis
Basophilic stippling
Nucleated red cells in peripheral blood, especially after
splenectomy
Reticulocyte count is elevated
HbF level is eleveated
 -Thalasemia
0-Thalasemia : no detactable -chain synthesis
absent chain mRNA
+-Thalasemia : reduced -chain synthesis
reduced or nonfunctional chain mRNA
Hereditary persistence of fetal hemoglobin
-Thalasemia : and -chain genes deleted
Hb Lepore : and -chain genes partially deleted
 - Thalasemia
c-Thalasemia 1 : deletion of 2 -genes
-Thalasemia 2 : deletion of -gene
Hb Constant spring : abnormal -chain variant
 Heterozygous states of -Thalasemia

Type Hb A2 Hb F

+- Thalasemia increased N to slightly increased

N to slightly increased
0- Thalasemia increased

- Thalasemia Normal Increased (2% - 10%)

HPFH Normal Increased (10% - 40%)

 Homozygous states of -Thalasemia

Type Anemia - globin - globin - globin - globin

chain chain mRNA Genes

-Thalasemia Severe Present Decreased Decreased Present

0-Thalasemia Severe Present Absent Absent or Present

abnormal

-Thalasemia Mild Absent Absent Absent Deleted

HPFH None Absent Absent Absent Deleted

-Thalasemia, Homozygous Forms (Major and intermedia)
Pathogeneses

Variable reduction of - chain syntheses (0, +, and

variant)
-chain excess result in intracellular precipitation of in
soluble - chain
Increased but ineffective erythropoesis with many red cell
precursors destroyed is related to - chain excess
Shortened red cell life span and variable splenic
sequestration
-Thalasemia, Homozygous Forms (Major and intermedia)
SEQUELAE

Hyperplastic marrow: bone marrow expansion with cortical thinning

Increased iron absorption and iron overload (caused of repeated blood
transfusion)
Cirrhosis of the liver
Endocrine disturbances e.g diabetes mellitus
Skin hyperpigmentation
Cardiac hemosiderosis
Hypersplenism
Plasma voleme expansion
Shortened red cell life
Leukopenia
thrombocytopenia
-Thalasemia, Homozygous Forms (Major and intermedia)
HEMATOLOGY

Anemia: hypochromic, microcytic, low MCV

Reticulocytosis
Leukopenia and thrombocytopenia (may develop)
Blood film : target cells and nucleated red cell, anisocytosis,
polychromasia, basophilia, circulating normoblast
Red cell life span reduced
HbF raised, HbA2 normal
Bone marrow may be megaloblastic(due to folate depletion), erythroid
hyperplasia
Osmotic fragility decreased
Serum ferritin raised
-Thalasemia, Homozygous Forms (Major and intermedia)
BIOCHEMISTRY

Raised bilirubin (chiefly indirect reacting)

Liver dysfunction
Endocrine abnormality : diabetes, hypogonadism
-Thalasemia, Homozygous Forms (Major and intermedia)
CLINICAL FEATURES

Failure to thrive
Anemia
Jaundice
Hepatosplenomegaly
Abnormal facies(prominence of malar eminances, frontal bossing, depression of bridge of nose, exposure
of upper central teeth)

Skull radiographs hair on end appearance

Fracture (caused of marrow expansion)
osteoporosis
Growth retardation ( primary amenorrhea, delayed puberty)
Leg ulcer
If untreated, 80% die in the first year of life
Clinical features ( thalasemia)
Severe form of thalasemia (Homozygous or
Compound heterozygous) present within the
first year of life
Failure to thrive
Mongoloid face
Poor feeding
Frequent infection
General malaise
Pale
Splenomegaly
Frequent transfusion hemosiderosis
 Complication
as a result of these situation

Inadequate treatment in the first years of life

Poor compliance
Excessive blood consumption
Insufficient application of chelating agent
 Complication

Endocrine disturbances (retarded growth, delayed puberty,

diabetes, hypogonadism, adrenal insufficiency, hypothyroidism,
)
hypoparathyroidism

Liver cirrhosis
Cardiac failure
Spinal compression caused by epidural extramedullary
hematopoesis
 Causes of death
Hepatic and cardiac failure
Increased susceptibility to infection post
splenectomy
 Management
Hypertransfusion to maintain pretransfusion
Hb 10.5 11 g/dl
Growth and development are maximized
Extramedullary hemapoesis is minimized decreasing
facial and skeletal abnormalities
Number of - chain precipitate are reduced prevent
development of splenomegaly and hypersplenism
Chelation therapy iron chelating agent
(desferioxamine)
Splenectomy
Supportive care
 Clinical management
Regular Red cell transfusions
< 6 g/dl at monthly interval
Low transfusion , not exceeding 9.5 g/dl
High trnsfusion, exceeded 11 g/dl
Iron overload iron chelating therapy with
deferoxamine
Splenectomy
Bone marrow transplantation
 Splenectomy
Reduces transfusion requirements in
hypersplenism
Prophylactic pneumococcal and hemophilus
influenza B vaccine and prophylactic life-long
penicilline are needed.
Indication :
Persistent increase of blood transfusion requirement
Evidence of severe leukopenia and thrombocytopenia
 Supportive care
Folic acid is not necessary in hypertransfusion; 1
mg daily is needed in untranfused(intermedia
patients)
Hepatitis B vaccination
Digitalis and diuretics in congestive heart failure
Endocrine intervention : thyroxine,
estrogen,testoteron
Cholescystectomy
Genetic counseling and antenatal diagnosis
 Gene therapy
Insertion of normal globin gene into marrow
stem cells
The technique is not fesiable in the near
future
 -Thalasemia Intermedia
CLINICAL FEATURES
Incidence : 2 10%
Syndrome is clinically milder than thalasemia
mayor
Generally do not require transfusion and maintain
Hb 7 10 g/dl
Hepatosplenomegaly, growth retardation,
hyperbilirubinemia, iron over load
Parvovirus B19 infection induces transient
erythroblatopenia(aplastic crisis)
 -Thalasemia Intermedia
Management
Folic acid 1 mg daily orally
Diet : avoid eating food which is rich in iron
Chelating therapy, when serum ferritin has
risen >2,000 ng/ml
Tranfusion are not required; except aplastic
crises, acute infection
Splenectomy may be required
 -Thalasemia Minor or Trait (Heterozygous 0 or +)
CLINICAL FEATURES

Asymptomatic
Discovered on routine blood test: slightly reduced hemoglobin,
basophilic stippling, low MCV, normal RDW
Discovered in family investigation or family history
Mild anemia
Physical examination normal
 -Thalasemia Minor or Trait (Heterozygous 0 or +)
DIAGNOSIS

Hb normal or slightly decreased

Hypochromic, microcytic cells, target cells, anisocytosis,
basophilic stippling, low MCV, normal RTDW
Hemoglobin A2 increased >4%, Hb F midly elevated in
50% cases
 Prevention
Premarital counselling
Diagnostic Prenatal
Amniocentesis
Villous sampling