THALASSEMIAS

Basic Features
 Thallasemia syndromes are characterized by
varying degrees of ineffective hematopoiesis and
increased hemolysis
 Clinical syndromes are devided into α- and β-
thallasemias
 Most β-thallasemias are due to point mutations in
one or both of the two β-globin genes
(chromosome 11)
 Most α-thallasemias syndromes are due to
deletion of one or more of the α-globin genes
rather than to point mutations
Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005
Epidemiology
 Although β-thallasemia has >200
mutations, most are rare
 Approximately 20 common alleles
constitute 80 of the known thallasemias
worldwide; 3% of the world’s population
carries gene for β-thallasemia, and in
Southeast Asia 5-10% of the population
carries genes for α-thallasemia
DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
β-Thalassemia
 β0-Thallasemia
 β+-Thallasemia
 δβ-Thallasemia
 Εβ-Thallasemia
 Hb Lepore

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
α-Thalassemia
 Silent carrier α-thallasemia
 α-thallasemia trait
 Hb Constant Spring
 HbH disease
 Hydrops fetalis

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
β-Thalassemia: Homozygous or
Doubly Heterozygous Forms
Pathogenesis
 Variable reduction of β-chain synthesis
 Relative α-globin chain excess resulting in
intracellular precipitation of insoluble α-chains
 Increased but ineffective erythropoiesis with
many red cell precurcors prematurely destroyed;
related to α-chain excess
 Shortened red cell life span; variable splenic
sequestration

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

Sequelae
 Hyperplastic marrow
 Increased iron absorption and iron overload
 Hypersplenism

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

Hematology
 Anemia: Hypochromic, microcytic
 Reticulocytosis
 Leukopenia and thrombocytopenia
 Blood smear: target cells and nucleated red cells, extreme
anisocytosis, contracted red cells, polychromasia,
punctate basophilia, circulating normoblast
 Hemoglobin Fraised; hemoglobin A2 increased
 Bone marrow: May be megaloblastic (due to folate
depletion); eryhtoid hyperplasia
 Osmotic fragility: decreased
 Serum ferritin: raised

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
Clinical Features
 Failure to thrive in early childhood
 Anemia
 Jaundice
 Hepatosplenomegaly
 Abnormal facies, prominence of malar eminences, frontal
bossing, depression of bridge of the nose, and exposure of
upper central teeth
 Growth retardation, delayed puberty, primary amenorrhea
in females
 Leg ulcers
 Skin bronzing
Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005
DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
Management
 Hypertransfusion Protocol, is used to maintain a
pretransfusion Hb between 10.5 and 11.0 g/dL
 Hypertransfusion results in:
 Maximizing growth and development
 Minimazing extramedullary hematopoiesis and
decreasing facial and skeletal abnormalities
 Reducing excessive iron absorption from gut
 Retarding the development of slenomegaly and
hypersplenism
 Reducing and/or delaying the onset of complications
Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005
DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
 …management
 Chelation Therapy
The objectives:
 To bind free extracellular iron
 To remove excess intracellular iron
 To attain a negative iron balance

 Iron overload results from:

 Ongoing transfusion therapy
 Increased gut absorption of iron
 Chronic hemolysis
Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005
DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
 …management
 Desferrioxamine (Desferal):
 Chelation should be instituted when the
ferritin level is >1000 ng/mL and adequate
iron is excreted into the urine with the
desferrioxamine challenge
 Dose: 40-60 mg/kg/day, is infused
subcutaneously over 8-10 hours

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
 …management
 Splenectomy
 Splenectomy reduces the transfusion requirements in
patients with hypersplenism
 Two weeks prior to splenectomy, a polyvalent
pneumococcal and meningococcal vaccine should be
given
 Indications:
 Persistent increase in blood requirements by 50% or more
over initial needs for more than 6 months
 Annual packed cell transfusion >250 mL/kg/year
 Evidence of severe leukopenia and/or thrombocytopenia

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
 …management
 Supportive Care
 Folic acid
 Hepatitis B vaccination
 Endocrine intervention
 Genetic counceling and antenatal diagnosis

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
 …management
 Deferiprone (L1)
 Dose: 75 mg/kg/day
 ICL-670
 Hematopoietic Stem Cell Transplantation

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
β-Thalassemia Intermedia
Clinical Features
 Patients generally do not require transfusions and
maintain a Hb between 7 and 10 g/dL
 Marked medullary expansion,
hepatosplenomegaly, growth retardation, facial
anomalies, and hyperbilirubinemia occur if
patients are not adequately transfused
 Patients are most healthy if managements is as
vigorous as that for thallasemia major

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

β-Thalassemia Minor or Trait
(Heterozygous β0 or β+)
Clinical Features
 Asymptomatic (physical examination is
nomal)
 Thalassemia trait or unusual severity

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

α-Thalassemia
 Hemoglobin H disease is clinically milder
than homozygous β-thalassemia and does
not require a hypertransfusion protocol
 Hydrops fetalis is not compatible with life
and presents with intrauterine or neonatal
death

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

Thank You…
Indikasi Rawat pada Penderita ITP
Akut:
 Jumlah trombosit <20.000/mm3
 Perdarahan berat tanpa melihat jumlah trombosit
 ITP akut: ringan + ptekhie/ekimosis dengan
jumlah trombosit <20.000/mm3
 Didapat atau adanya kecurigaan perdarahan
intrakranial
 Usia <3 tahun
 Permintaan orangtua
Indikasi Pemberian Trombosit
 Trombosit <20.000/mm3 dan disertai demam
 Trombosit <5.000/mm3 dengan kemungkinan
kecil akan naik dalam beberapa hari
 Trombosit <150.000/mm3 dan akan menjalani
operasi
 Trombosit berapa pun dengan perdarahan hebat