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THALASSEMIAS

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Basic Features Thallasemia syndromes are characterized by

varying degrees of ineffective hematopoiesis and

increased hemolysis Clinical syndromes are devided into - and -

thallasemias

Most -thallasemias are due to point mutations inone or both of the two -globin genes(chromosome 11)

Most -thallasemias syndromes are due todeletion of one or more of the -globin genesrather than to point mutations

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005

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Epidemiology

Although -thallasemia has >200

mutations, most are rare Approximately 20 common alleles

constitute 80 of the known thallasemias

worldwide; 3% of the worlds population

carries gene for -thallasemia, and in

Southeast Asia 5-10% of the population

carries genes for -thallasemia

DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007

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-Thalassemia

0-Thallasemia

+

-Thallasemia -Thallasemia

-Thallasemia

Hb Lepore

Lanzkowsky P. Manual of Pediatric Hematology and Oncology. 2005DeBaun M, Vichinsky E. Nelson Textbook of Pediatrics. 2007

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-Thalassemia

Silent carrier -thallasemia

-thallasemia trait Hb Constant Spring

HbH disease

Hydrops fetalis


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-Thalassemia: Homozygous or

Doubly Heterozygous Forms

Pathogenesis

Variable reduction of -chain synthesis

Relative -globin chain excess resulting inintracellular precipitation of insoluble -chains

Increased but ineffective erythropoiesis withmany red cell precurcors prematurely destroyed;related to -chain excess

Shortened red cell life span; variable splenicsequestration


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Sequelae

Hyperplastic marrow

Increased iron absorption and iron overload Hypersplenism


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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 folatedepletion); eryhtoid hyperplasia

Osmotic fragility: decreased

Serum ferritin: raised


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Clinical Features Failure to thrive in early childhood

Anemia

Jaundice Hepatosplenomegaly

Abnormal facies, prominence of malar eminences, frontalbossing, depression of bridge of the nose, and exposure ofupper central teeth

Growth retardation, delayed puberty, primary amenorrheain females

Leg ulcers

Skin bronzing


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Management Hypertransfusion Protocol, is used to maintain a

pretransfusionHb between 10.5 and 11.0 g/dL

Hypertransfusion results in: Maximizing growth and development

Minimazing extramedullary hematopoiesis anddecreasing 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


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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


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management

Desferrioxamine (Desferal):

Ch

elation sh

ould be instituted when t

heferritin level is >1000 ng/mL and adequate

iron is excreted into the urine with the

desferrioxamine challenge

Dose: 40-60 mg/kg/day, is infusedsubcutaneously over 8-10 hours


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management Splenectomy

Splenectomy reduces the transfusion requirements in

patients withhypersplenism Two weeks prior to splenectomy, a polyvalent

pneumococcal and meningococcal vaccine should begiven

Indications:

Persistent increase in blood requirements by 50% or moreover initial needs for more than 6 months

Annual packed cell transfusion >250 mL/kg/year

Evidence of severe leukopenia and/or thrombocytopenia


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management

Supportive Care

Folic acid Hepatitis B vaccination

Endocrine intervention

Genetic counceling and antenatal diagnosis


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management

Deferiprone (L1)

Dose: 75 mg/kg/day ICL-670

Hematopoietic Stem Cell Transplantation


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-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, facialanomalies, and hyperbilirubinemia occur if

patients are not adequately transfused Patients are most healthy if managements is as

vigorous as that for thallasemia major


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-Thalassemia Minor orTrait

(Heterozygous 0 or +)

Clinical Features

Asymptomatic (physical examination isnomal)

Thalassemia trait or unusual severity


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-Thalassemia

Hemoglobin H disease is clinically milder

than homozygous -thalassemia and does

not require a hypertransfusion protocol

Hydrops fetalis is not compatible with life

and presents with intrauterine or neonatal

death


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Thank You

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