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β – Thalassemias Prepared By : Group E , PBL Presented By : ______ ___

β Thalassemia

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Thalassemia

ThalassemiasPrepared By : Group E , PBLPresented By : ______ ___ Group E, Problem Based LearningMembersPranodan PoudelAnup SubediRobin Jung BhandariRiyaz ShresthaMonica BoharaSumina RaiKaruna RayamajhiPuja Pahari

Swati DhungelDibasha AdhikariPrabha BhandariKipa Shrestha

Tutor : Dr. Sajana K.C.IntroductionDisorder of Hemoglobin.Decreased production of globin chain.In Hemoglobinopathy, globin chains are abnormal.DefinitionThalassemia is a heterogenous group of disorders characterized by genetically determined reduction in the rate of synthesis of normal globin chains.

HemoglobinFetal Hemoglobin, HbF (2 + 2)Adult Hemoglobin, HbA (2 + 2)

Thalassemia : EtiopathogenesisAutosomal recessive disorder.Each chromosome of chromosome number 11 has one allele for the gene to encode beta globin.Point mutation in the beta gene leads to absence or decreased production of beta globin chains.

Etiopathogenesis- It occurs due to gene mutation.On the basis of occurrence of gene mutations thalassemias are of two types: Thalassemia - absence of globin chains + Thalassemia - decresed production of globin chainsEtiopathogenesis - + Thalassemia

Etiopathogenesis - + Thalassemia

Etiopathogenesis 0 Thalassemia

Etiopathogenesis 0 Thalassemia

Mutated genesReduced chains synthesisDecreased HbAExcess chainsDecreased O2 DeliveryHepatosplenomegalySplenic HemolysisPeripheral Blood CirculationDeranged RBC membranes, ApoptosisChains precipitationBone Marrow PhagocytosisIneffective ErythropoiesisAnemiaIncreased ErythropoietinIncreased IronToxicityIncreased ErythropoiesisFractures and Mongoloid FacesBone Marrow ExpansionTypes Thalassemia Minor Thalassemia Major Thalassemia Minor

Genotype ( / +)Asymptomatic to Mild Anemia.RBCs are increased in some cases. Thalassemia MajorGenotype (0 / 0) or, (+ / +) globin chains are not produced at all owing to defective genes.Decreased amount of HbA, Major Red cell HbHbFThe 4 tetramers are formed.RBC containing these tetramers are destroyed in Bone Marrow (Ineffective Erythropoiesis) or in Spleen.This leads to Anemia.Bone marrow becomes hyperactive to produce more RBCs.

Thalassemia Major Thalassemia Major Thalassemia MajorSimilar expansions of marrow in facial bones give rise to RODENTS FACE or, CHIPMUNK Appearance.

Hair on end / Crew-Cut Appearance of Skull on Radiography

Rodents Face / Chipmunk AppearanceClinical FindingsIrritabilityPallorDiarrheaFeverEnlarged AbdomenCardiac failure in 1st decade of lifeSevere AnemiaGrowth RetardationBone ChangesHepatosplenomegaly(due to extramedullary hematopoiesis)Basophilic StipplingFig:

Basophilic Stippling and Dacrocyte (Teardrop Cell)Basophilic stippling /Punctate basophilia refers to an observation found when observing a blood smear in which erythrocytes display small dots at the periphery. These dots are the visualization of ribosomes.Laboratory FindingsSevere Anemia (2-3 g/dl)Decreased Mean Cell VolumeDecreased Mean Cell Hb ConcentrationLaboratory FindingsMicrocytic Hypochromic PictureAnisopoikilocytosis

Laboratory FindingsTarget Cells

Target CellsFig:Peripheral smear from a patient with beta-zero thalassemia major showing more marked microcytosis (M) and anisopoikilocytosis (P) than in thalassemia minor. Target cells (T) and hypochromia are prominent.

Laboratory FindingsIf Microcytic Hypochromic smear with nucleated RBCs is obtained from a child patients blood sample, the case is always of Thalassaemia.Alpha Thalassemia Absence or decreased production of alpha globin chains

Two alpha globin genes on each chromosome 16

The types of alpha thalassemia result from deletion of one or more of these genes

Clinical SyndromesSilent carrier Deletion of single -globin gene

Not much reduction in -globin chain synthesis

Individuals are completely asymptomatic

Clinical Syndromes-thalassemia traitDeletion of two -globin genes

Can be from the same chromosome or one from each chromosome

Clinical SyndromesHemoglobin H diseaseDeletion of 3 -globin genes

-globin synthesis markedly reduced

Tetramere of beta-globin (4)- Hb H

Hb-H very high affinity to O2- tissue hypoxia

Hb H prone to oxidation- formation of intracellular inclusions- removed by splenic macrophages

Clinical SyndromesHydrops fetalisMost severe from

Deletion of all 4 globin genes

In fetus, excess -globin chain form tetramere (Hb Barts)

Hb Barts- very high affinity to O2, delivers almost no O2

Clinical SyndromesHydrops fetalis

Severe tissue hypoxia- intrauterine death

Fetus- severe pallor, generalized edema, and massive hepatosplenomegaly

Clinical Syndromes

Silent carrier

Alpha thalassemia trait

Hemoglobin H disease

Hydrops fetalis