THALASEMIA definition and pathophysiologyd].pptx

thalassemia introduction and pathophysiology

1. THALASSEMIA Dr.sehrish chaudhary pgy1 transfusion medicine/ ihbt

2. THALASSEMIA INTRODUCTION DEFINITION INCIDENCE CAUSES AND TYPES PATHOPHYSIOLOGY CLINICAL FEATURES DIAGNOSTIC EVALUATION & MANAGEMENT

3. INTRODUCTION TO THALASEMIA world thalassemia day theme 2024-empowering lifes,embracing progress: equitable and accessible thalassemia treatment for all.

4. THE WORD “THALASSEMIA” IS DERIVED FROM THE GREEK WORD “THALASSA” MEANS THE GREAT SEA. THE DISEASE WAS FIRST DISCRIBED BY COOLEY IN 1953. THALASSEMIA IS A GROUP OF DISEASE OF HEREDITARY HEMOLYTIC ANEMIA CHARACTERISED BY REDUCTION IN THE SYNTHESIS OF HB. IT PRODUCES HYPOCHROMIC MICROCYTIC ANAEMIA DUE TO DEFETIVE HEMOGLOBINIZATION OF RBC’S,HEMOLYSIS AND INEFFECTIVE ERYTHROPOISES.

5. INTRODUCTION The thalassemia is a blood disorder passed down through families (inherited) in which the body makes an abnormal form of Hb . Haemoglobin ( Hb ) is the protein in RBC’s that carries oxygen. The disorder results in large no. of RBC’s being destroyed, which leads to Anaemia. 5

6. DEFINITION Thalassemia is an autosomal recessive genetic disorder that results in inadequate normal haemoglobin production. It is an inherited blood disorder in which the body produces an abnormal form of hb which results in excessive destruction of red blood cells and further leads to anemia . Types - 7 Alpha thalassemia Beta thalassemia

7. NORMAL RBC VS ABNORMAL RBC’S 8 MALFORMED RBC’S

8. INCIDENCE Commonly found in members of ethnic groups whose origin are near the Mediterranean sea or equatorial or near equatorial regions of Asia, the middle east and Africa. Beta thalassemia major is the commonest group of autosomal recessive disorder in India. Carrier frequency varies from 3% to 17% in different populations, with over 30 million people carrying the defective gene. INDIA has the largest number of children with thalassemia major in the world viz 1 to 1.5 lac (almost 42 million carriers of beta thalasemia trait. About 10k-15k babies are born with beta thalassemia major are born every year. In US there is 1 th minor patient/2.27 lac population but in india the ratio is 1 -25 %,which is alarming. 9

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10. 11 CAUSES Haemoglobin molecule is made up of 4 heme groups surrounding a globin group forming a tetrahedral structure,consisting of 2 alpha sub-units and 2 beta sub units.(structurally similar about the same size). Hb is made up of two globular proteins: i )alpha globin ii)beta globin Thalassemia occurs when there is defect in a gene that helps in control production of one of these proteins (abnormal hb synthesis). Risk factor for thalassemia include: 1.family history of disorder. 2.asian,chinese,mediterranean,or african-american ethnicity.

11. 12 Types of hb -pre-dominant type hb A Hb-A2 :2 alpha sub-units & 2 gamma sub units. Hb F:2 alpha & 2 delta units.

12. 13 Two types of thalassemia: 1 ) Alpha thalassemia :- When there is disturbance in production of alpha globin from any or all four of the alpha globin genes.(encoded on chr 16 while the gamma,delta & beta globin genes are encoded on chr11) Alpha globin chains are absent / reduced in this type of thalassemia. Alpha trait(heterozygous state)is asymptomatic in about 30% of African Americans. Alpha thalassemia occur most often in people from Southeast Asia, Middle East, China, And those of African descent. . Types

13. Pathophysiology of alpha thalassemia A lpha thalassemia occurs when there is a disturbance in production of a- globin from any or all four of the a- globin genes. When functional point mutations, frame shift mutations, nonsense mutations, and chain termination mutations occur within or around the coding sequences of the alpha- globin gene cluster hemoglobin is impaired . protein synthesis may be inhibited . Normal production of alpha chains is absent excess production of gamma- globin chains in the fetus and newborn or beta- globin chains in children and adults. 14

14. The B- globin chains are capable of forming soluble tetramers (beta-4, or HbH ) This form of hemoglobin is still unstable and precipitates within the cell, forming insoluble inclusions called Heinz bodies . Heinz bodies damage the red blood cells . R esults in damage to erythrocyte precursors and ineffective erythropoiesis in the bone marrow, hypochromia and microcytosis of circulating red blood cells. 15

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17. 2 ) Beta thalassemia :- When 'similar gene defects' affect the production of beta globin protein. Beta globin chains are absent or reduced in this type of thalassemia. Specifically, it is characterized by a genetic deficiency in the synthesis of beta- globin chains. Beta- globin is a component (subunit) of hemoglobin. 18

18. . 19 Types Thalassemia Major aka (Cooley's anemia)- -severe form of beta thalassemia - presence of two abnormal genes that cause either a severe decrease or complete lack of beta globin production. . Thalassemia Minor presence of one normal gene and one with a mutation - causes mild to moderate anemia. 1 ) Thalassemia major :-It is developed by inherited gene defect from both parents. A homozygous person has two thalassemic genes, causing a severe condition known as thalassemia major. Those who inherit both beta- genes (homozygote) have thalassemia major, which results in a profound and life threatening anemia.

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20. 2) Thalassemia minor :- It includes the receiving of faulty gene from the only one parent. Those who inherit just one beta gene (heterozygote) have thalassemia minor also called the thalassemia trait, the carrier state of thalassemia. A person who is heterozygous has one thalassemic gene and one normal gene and is said to have thalassemia minor (or thalassemic trait), which is a mild form of disease. 21

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22. Etiology Beta thalassemia is caused by a deficiency of Beta globin inherited in an autosomal recessive pattern, which means both copies of the HBB(Hemoglobin beta) gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition 23

23. Pathophysiology In Beta thalassemia major, patients have severe anemia, ineffective erythropoiesis , extramedullary hematopoiesis , and iron overload resulting from transfusion and increased iron absorption. The skin may show pallor from anemia and jaundice from hyperbilirubinemia . The skull and other bones may be deformed secondary to erythroid hyperplasia with intramedullary expansion and cortical bone thinning. Heart examination may reveal findings of cardiac failure and arrhythmia, related to either severe anemia or iron overload. Abdominal examination may reveal changes in the liver, gallbladder, and spleen. Patients who have received blood transfusions may have hepatomegaly or chronic hepatitis due to iron overload. 24

24. Pathophysiology ctd ... The gallbladder may contain bilirubin stones formed as a result of the patient's lifelong hemolytic state. Splenomegaly typically is observed as part of the extramedullary hematopoiesis or as a hypertrophic response related to the extravascular hemolysis . In addition to cardiac dysfunction, hepatomegaly , and hepatitis, iron overload can also cause endocrine dysfunction, especially affecting the pancreas, testes, and thyroid. Transfusion-associated viral hepatitis resulting in cirrhosis or portal hypertension also may be seen. 25

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27. Clinical manifestation Individual with alpha-thalassemia may have mild anemia & are typically asymptomatic. (most severe form of alpha thalassemia major causes stillbirth). Children born with beta-thalassemia major (Cooley anemia) are normal at birth, but develop severe anemia during first year of life. Individual with thalassemia major are diagnosed early in life because the lack of Hb becomes quickly apparent. Affected children appear normal at birth because fetal Hb contain no beta- globin ; in first few months, manifestations of severe anemia begin to appear.

28. 29 children also have pain, failure to thrive, frequent infections, diarrhoea , spleenomegaly , hepatomegaly , jaundice from rbc hemolysis , and bone marrow hyperplasia. other symptoms are:- bone deformities in face.- fatigue.- growth failure.- shortness of breath.- yellow skin (jaundice ). C.F ctd ..

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