thallasmia
DESCRIPTION
TRANSCRIPT
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"Pleasure in the job puts perfection in the work." -- Aristotle :
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Hemoglobinopathies
are disorders affecting the structure, function or
production of hemoglobin
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Thalassemia is one of them
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• Hemoglobin • Haem + Globin
• Globin – 4 chains - , , ,■ - 3 Types • HbA (Normal Hemoglobin- 22) • HbF ( 2 2 – Fetal Hemoglobin)• HbA2 (22 ) • Each chain has specific aminoacid combination • When aminoacids altered by deletion or addition, mutation – abnormal hemoglobins are formed.
Thalassemia
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• Hemoglobin critical for normal oxygen delivery to tissues• Normal RBC life span – 120 days • Hemoglobin is present in erythrocytes in such high quantities that it can alter red cell shape, deformability and viscosity.
Thalassemia
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Hemoglobin Review
• Each complex consists of :– Four polypeptide chains, non-covalently
bound
– Four heme complexes with iron bound
– Four O2 binding sites
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Globin Chains• Alpha Globin
– 141 amino acids– Coded for on Chromosome 16– Found in normal adult hemoglobin, A1 and A2
• Beta Globin– 146 amino acids– Coded for on Chromosome 11, found in Hgb A1
• Delta Globin – Found in Hemoglobin A2--small amounts in all adults
• Gamma Globin– Found in Fetal Hemoglobin
• Zeta Globin– Found in embryonic hemoglobin
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Hemoglobin Types
Hemoglobin Type
• Hgb A1—92%---------
• Hgb A2—2.5%--------
• Hgb F — <1%---------
• Hgb H ------------------
• Bart’s Hgb--------------
• Hgb S--------------------
• Hgb C-------------------
Globin Chains gluval
glulys
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• Thalassemias are genetic disorders in which synthesis of normal polypeptide chain forming adult hemoglobin is suppressed. • Selective deficiency of one or more polypeptide chains have two consequences
• 1. Hb – Anemia & Erythropoeisis • 2. Cell Membrane damage leading to premature destruction of cells
Thalassemia
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• Decreased production of chains. • Total 4 genes code for 4 chains
• 2 genes on each chromosome 16
-Thalassemia
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• 2 Classifications • First Type a. Thalassemia Major (Profound Anemia) b. Thalassemia Intermediate c. Thalassemia Minor d. Thalassemia Minima • Second Type a. Alpha Thalassemia b. Beta Thalassemia
Types of Thalassemia
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-Thalassemia • Classification - -Thalassemia 2 trait (One of 4 genes deleted) - -Thalassemia 1 trait (Two of 4 genes deleted) - HbH disease > Three genes deleted > No specific treatment required > Avoid iron therapy > Folic acid if necessary - Hydrops fetalis (Hb Bart’s) > All 4 genes deleted > In utero death of foetus > No treatment available
-Thalassemia
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Alpha Thalassemias
• Result from gene deletions• One deletion—Silent carrier; no clinical
significance• Two deletions— Thal trait; mild
hypochromic microcytic anemia• Three deletions—Hgb H; variable
severity, but less severe than Beta Thal Major
• Four deletions—Bart’s Hgb; Hydrops Fetalis; In Utero or early neonatal death
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Alpha Thalassemias
• Usually no treatment indicated
• 4 deletions incompatible with life
• 3 or fewer deletions have only mild anemia
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• Point mutation in gene for non alpha producing chain in chromosome 11 - Two types
• Beta Thalassemia Major ( 0 ) • Beta Thalassemia Minor ( - )
Beta Thalassemia
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Also called Cooley’s Anemia
• Clinical Features - Severe hypochromic anemia - Erythroblastosis - Grossly HbA - Increase in HbF
Beta Thalassemia Major
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• Treatment - Bone Marrow transplantation
- Avoid Iron therapy
- If iron overload, Desferoximine therapy - Splenectomy
Beta Thalassemia Major
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• Clinical Features - Mild anemia - Some target cells - Punctate basophilia - resistance of RBC to osmotic lysis
Beta Thalassemia Minor
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-Thalassemia Major--Treatment• Chronic Transfusion Therapy
– Maximizes growth and development
– Suppresses the patient’s own ineffective erythropoiesis and excessive dietary iron absorption
– PRBC transfusions often monthly to maintain Hgb 10-12
• Chelation Therapy– Binds free iron and reduces hemosiderin deposits
– 8-hour subcutaneous infusion of deferoxamine, 5 nights/week
– Start after 1year of chronic transfusions or ferritin>1000 ng/dl
• Splenectomy--indications– Trasfusion requirements increase 50% in 6mo
– PRBCs per year >250cc/kg
– Severe leukopenia or thrombocytopenia
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-Thalassemia Major Complications and Emergencies
• Sepsis—Encapsulated organisms– Strep Pneumo
• Cardiomyopathy—presentation in CHF– Use diuretics, digoxin, and deferoxamine
• Endocrinopathies—presentation in DKA– Take care during hydration so as not to
precipitate CHF from fluid overload
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How to Prevent Thalassemia
This disease is inherited. Blood tests and family genetic studies will show if you are a carrier. A genetic counselor can discuss risks of passing on the disease. They can also give you information on testing.