بنام خدا

1. بنام خدا

2. Thalassemia Dr.Alireza Nikanfar Hematology and oncology research center of Tabriz University of Medical Sciences

3. Hemoglobin Structure • tetramer of globin polypeptide chains: a pair of α -like chains 141 amino acids long and a pair of ß -like chains 146 amino acids long • The major adult hemoglobin, HbA, has the structure α2 ß2. HbF (α2γ2) predominates during most of gestation, and HbA2 (α2δ2) is a minor adult hemoglobin.

4. Hemoglobin Structure • Each globin chain enfolds a single heme moiety, consisting of a protoporphyrin IX ring complexed with a single iron atom in the ferrous state (Fe2+), • Each heme moiety can bind a single oxygen molecule; every molecule of hemoglobin can thus transport up to four oxygen molecules.

8. Thalassemia Syndromes • inherited disorders of α- or ß-globin biosynthesis • The reduced supply of globin diminishes production of hemoglobin tetramers, causing hypochromia and microcytosis. • Unbalanced chain accumulation dominates the clinical phenotype

9. α-Thalassemia Syndromes • α-thalassemia-2 trait, in which one of the four α-globin loci is deleted • α -thalassemia-1 trait, with two deleted loci • HbH disease, with three loci deleted • hydrops fetalis with Hb Bart's, with all four loci deleted • Nondeletion forms

11. α-Thalassemia Syndromes • α -Thalassemia-2 trait is an asymptomatic, silent carrier state. • α-Thalassemia-1 trait resembles -thalassemia minor • Heterozygosity for a deletion that removes both genes from the same chromosome (cis deletion) is common in Asians and Mediterranean individuals, as is homozygosity for -thalassemia-2 (trans deletion). Both produce asymptomatic hypochromia and microcytosis.

13. α-Thalassemia Syndromes • In HbH disease, HbA production is only 25 to 30% of normal • In adults, unpaired chains accumulate and are soluble enough to form ß4 tetramers called HbH • Patients with HbH disease have thalassemia intermedia characterized by moderately severe hemolytic anemia but milder ineffective erythropoiesis • Survival into midadult life without transfusions is common.

18. α-Thalassemia Syndromes • The homozygous state for the α-thalassemia-1 cis deletion (hydrops fetalis) causes total absence of α-globin synthesis • Excess γ globin forms tetramers called Hb Bart's (γ4), which has an extraordinarily high oxygen affinity • It delivers almost no O2 to fetal tissues, causing tissue asphyxia, edema (hydrops fetalis), congestive heart failure, and death in utero.

19. ß -Thalassemia Syndromes • Mutations causing thalassemia can affect any step in the pathway of globin gene expression: • Hypochromia and microcytosis • In heterozygotes (ß -thalassemia trait), this is the only abnormality seen; anemia is minimal.

22. ß -Thalassemia Syndromes • In homozygous states accumulation of highly insoluble unpaired α chains, which form toxic inclusion bodies that kill developing erythroblasts in the marrow ineffective erythropoiesis • The few surviving red cells bear a burden of inclusion bodies, detected in the spleen, shortening the red cell life span and producing severe hemolytic anemia. • Erythroid hyperplasia can become exuberant and produce extramedullary erythropoietic tissue in the liver and spleen

23. ß -Thalassemia Syndromes • Massive bone marrow expansion deranges growth and development. • "chipmunk" facies • thinning and pathologic fracture of long bones and vertebrae due to cortical invasion by erythroid elements, • profound growth retardation

24. ß -Thalassemia Syndromes • Hemolytic anemia causes hepatosplenomegaly, leg ulcers, gallstones, and high-output congestive heart failure. • The conscription of caloric resources to support erythropoiesis leads to inanition, susceptibility to infection, endocrine dysfunction, and, in the most severe cases, death during the first decade of life.

25. ß -Thalassemia Syndromes • Severity is highly variable • Alleles associated with milder synthetic defects and coinheritance of α-thalassemia trait reduce clinical severity • HbF persists to various degrees in thalassemias.

27. ß -Thalassemia Syndromes • ß-thalassemia major • ß-thalassemia intermedia can survive without transfusion • ß-thalassemia minor and ß-thalassemia trait describe asymptomatic heterozygotes for ß thalassemia

31. Diagnosis • The diagnosis of ß-thalassemia major is readily made during childhood on the basis of severe anemia accompanied by hepatosplenomegaly; profound microcytosis; a characteristic blood smear ; and elevated levels of HbF, HbA2, or both. • Patients with ß-thalassemia intermedia exhibit similar stigmata but can survive without chronic hypertransfusion.

33. Diagnosis • ß-Thalassemia minor (i.e., ß thalassemia trait) usually presents as profound microcytosis and hypochromia with target cells but only minimal or mild anemia • The mean corpuscular volume is rarely >75 fL; the hematocrit is rarely <30 to 33%. • Hemoglobin electrophoresis classically reveals an elevated HbA2 (3.5 to 7.5%), but some forms are associated with normal HbA2 and/or elevated HbF.

34. Diagnosis • Persons with α-thalassemia trait may exhibit mild hypochromia and microcytosis, usually without anemia • HbA2 and HbF levels are normal. • HbH disease resembles ß-thalassemia intermedia, with the added complication that the HbH molecule behaves like a moderately unstable hemoglobin.

39. خسته نباشید متشکرم متشکرم خسته نباشید