thalassemia dr. dina
TRANSCRIPT
THALASSEMIAS
R. Dina Garniasih
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. 2005DeBaun 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. 2005DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
β-Thalassemia: Homozygous or Doubly Heterozygous FormsPathogenesis 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 F raised; 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. 2005DeBaun 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. 2005DeBaun 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. 2005DeBaun 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. 2005DeBaun 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. 2005DeBaun 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. 2005DeBaun 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. 2005DeBaun 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. 2005DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007
β-Thalassemia IntermediaClinical 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