Thalassemia Dr. Dina

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


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


Sequelae Hyperplastic marrow Increased iron absorption and iron overload Hypersplenism


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


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


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


…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


…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


…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


…management Supportive Care

Folic acid Hepatitis B vaccination Endocrine intervention Genetic counceling and antenatal diagnosis


…management Deferiprone (L1)

Dose: 75 mg/kg/day ICL-670 Hematopoietic Stem Cell Transplantation


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


β-Thalassemia Minor or Trait (Heterozygous β0 or β+)

Clinical Features Asymptomatic (physical examination is

nomal) Thalassemia trait or unusual severity


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


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

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Thalassemia Dr. Dina