"Pleasure in the job puts perfection in thework." -- Aristotle :
Hemoglobinopathiesare disorders affecting the structure, function or production of hemoglobin
Thalassemia is one of them
Thalassemia• Hemoglobin• Haem + Globin• Globin – 4 chains - , , ,■ - 3 Types• HbA (Normal Hemoglobin- 2 2)• HbF ( o• HbA2 (A2• 2 )• Each chain has specific aminoacid combination• When aminoacids altered by deletion or addition, mutation –abnormal hemoglobins are formed.
Thalassemia• Hemoglobin critical for normal oxygen delivery totissues• Normal RBC life span – 120 days• Hemoglobin is present in erythrocytes in such highquantities that it can alter red cell shape, deformability andviscosity.
Hemoglobin Review• Each complex consists of : – Four polypeptide chains, non-covalently bound – Four heme complexes with iron bound – Four O2 binding sites
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
Thalassemia• Thalassemias are genetic disorders in which synthesisof normal polypeptide chain forming adult hemoglobinis suppressed.• Selective deficiency of one or more polypeptidechains have two consequences• 1. R Hb – Anemia & e• 2. Cell Membrane damage leading to prematuredestruction of cells
2 -Thalassemia• Decreased production of chains.• Total 4 genes code for 4 chains• 2 genes on each chromosome 16
Types of Thalassemia• 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
> -Thalassemia -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
Alpha Thalassemias• Result from gene deletions• One deletion—Silent carrier; no clinical significance• Two deletions—α 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
Alpha Thalassemias• Usually no treatment indicated• 4 deletions incompatible with life• 3 or fewer deletions have only mild anemia
Beta Thalassemia• Point mutation in gene for non alpha producing chain inchromosome 11- Two types• Beta Thalassemia Major ( r 0 )• Beta Thalassemia Minor ( r - )
Beta Thalassemia Major Also called Cooley’s Anemia • Clinical Features - Severe hypochromic anemia - Erythroblastosis - Grossly b l HbA - Increase in HbF
Beta Thalassemia Major• Treatment - Bone Marrow transplantation - Avoid Iron therapy - If iron overload, Desferoximine therapy - Splenectomy
Beta Thalassemia Minor• Clinical Features - Mild anemia - Some target cells - Punctate basophilia - resistance of RBC to osmotic lysis
β-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
β-Thalassemia MajorComplications 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
How to Prevent ThalassemiaThis disease is inherited. Blood tests andfamily genetic studies will show if you area carrier. A genetic counselor can discussrisks of passing on the disease. They canalso give you information on testing.