Week 10 - Thalassemia PDF

Thalassemia Ma. Christy V. Gonzales, RMT, MPH School of Medical Technology Emilio Aguinaldo College MCC4 31 (Hematology 1) Lecture 5. Thalassemia Causes: reduced production of globin chains formation of structurally abnormal Hb 5.1 α-thalassemia Nomenclature: Normal haploid:...

Thalassemia Ma. Christy V. Gonzales, RMT, MPH School of Medical Technology Emilio Aguinaldo College MCC4 31 (Hematology 1) Lecture 5. Thalassemia Causes: reduced production of globin chains formation of structurally abnormal Hb 5.1 α-thalassemia Nomenclature: Normal haploid: αα Thalassemia: gene deletion One: -α (α thalassemia 2 or α+ thalassemia ) Two: -- (α thalassemia 1 or α° thalassemia) 5.1 α-thalassemia Genotype Description Disorder αα/αα Normal None -α/αα Heterozygous Silent carrier -α/-α Homozygous α-thalassemia --/αα Heterozygous minor --/αCSα Heterozygous Hb H/ Constant Spring Disease --/-α Heterozygous Hb H disease --/-- Homozygous Barts Hydrops fetalis 5.1 α-thalassemia Genotype Disorder Red Cell Hb Electorphoresis Morphology αα/αα None Normal Normal -α/αα Silent carrier Normal / Sl -α/-α α-thalassemia MCV, MCH Normal minor ++ Hb H incl. --/αα --/-α Hb H disease MCV, MCH Hb A, H (2-40%) +++ Hb H incl. ± Hb Barts Hb A2 --/-- Barts Hydrops MCV, MCH Hb Barts (80%) fetalis NRBC Hb Portland  5.1 α-thalassemia Disorder Demographics Anemia LE Silent carrier Asians, Chinese, Filipinos None Both: Southeast Asians, α-thalassemia Chinese, Filipinos None/ Mild minor Homo: Med. Blacks Hetero: rare in blacks Normal Hb H/ CS Orientals None/ Mild Disease Med. populations Hb H disease Southeast Asia, Med. Islands, Moderate Middle east Barts HF Southeast Asia, Med. Islands, Fatal Severe Middle east 5.1 α-thalassemia Hb H- Constant Spring Disease caused by compound hetero inheritance of Hb CS and α° thalassemia (--/αCSα) Hb CS 2 β chains + 1 normal α chain + 1 abnormal α chain (172 aa) deficit in normal α chain when inherited with double α gene deletion Hb H like disorders elongated alpha chain results from mutation of chain terminator codon 5.1 α-thalassemia Hb H Disease caused by deletion of 3 of 4 globin chains (--/-α) non deletional forms: (ααT / ααT) and (ααT /--) decreased synthesis of α chains formation of unstable Hb H (β4) 5.1 α-thalassemia Barts Hydrops Fetalis caused by deletion of 4 α globin chains (--/--) formation of Hb Barts (γ4) high affinity to oxygen not effective release of oxygen to tissues fatal Hb Portland survival into 3rd trimester of fetal life 5.2 β-thalassemia lack/reduced production of beta chains, excess of alpha chains massive imbalance: severe erythrocyte dysfunction result: ineffective erythropoiesis Classifications: Thalassemia major Severe anemia with iron overload Thalassemia intermedia Moderate anemia Thalassemia minor Asymptomatic; may or may not produce mild anemia Thalassemia minima No detectable clinical abnormalities 5.2 β-thalassemia Thalassemia major Genotypes: β°/ β° β+ / β+ Mediterranean form β°/β+ δβ (Lepore)/δβ (Lepore) Hb Lepore 2 normal alpha chains + 2 abnormal non-alpha chains formed by fusion of N-ter end of δ chain and C-ter end of β chain Baltimore, Boston, Hollandia 5.2 β-thalassemia Thalassemia intermedia Genotypes: β+ / β+ Mild Black form Americans and African blacks Less impairment of β chain synthesis than med. form (δβ)°/ (δβ)° Deletion of δ and β structural genes found in chrom 11 5.2 β-thalassemia Thalassemia minor Genotypes: Hetero β° (β°/ β) or β+ (β + / β) Beta thalassemia trait High-Hb A2 thalassemia Combination of normal β gene + either β+/ β° Hetero δβ: (δβ)°/ β Hetero Hb Lepore: (δβ) Lepore / β Thalassemia minor Genotypes: Heterozygous βSC  5.2 β-thalassemia Diagnosis RBC Red Cell Morphology Hb Electrophoresis count MCV, MCH Hb F Thalassemia ++ stippling Var. Hb A2 major +++ NRBC & target ± Hb A MCV, MCH N/ Hb F Thalassemia + stippling V. Hb A2 intermedia ± NRBC ± Hb A ++ target cells Thalassemia MCV, MCH N/ Hb F minor + stippling & target V. Hb A2 & Hb A Thalassemia Normal/ Sl. MCV & MCH, ± N N minima stippling & target 5.3 Hereditary Persistence of Fetal Hemoglobin increased Hb F in adults in the absence of usual clinical and hematologic features of thalassemia deletion/ inactivation of δ and β structural gene complex compensatory persistence of γ chain into adult Categories: Pancellular RBCs contain increased levels of Hb F (acid elution slide test) Heterocellular only subpopulation of RBCs contain inc. levels of Hb F British, Georgia, Swiss, Atlanta, Seattle 5. Thalassemia Laboratory diagnosis a. Hemoglobin electrophoresis Cellulose acetate (alkaline medium) Separates Hb variants (screening) Hb Barts, Hb CS, Hb Lepore Citrate agar (acid pH) Useful in differentiating abnormal hemoglobins w/c migrate together on cellulose acetate (Hb Lepore & Hb S) 5. Thalassemia Laboratory diagnosis b. Quantitation of Hb F Significantly increased Homo β° and β+ (Mediterranean form), δβ thalassemia, Hb Lepore, pancellular HPFH Moderate/ Sl. elevation Thalassemia minor and Heterocellular forms of HPFH 5. Thalassemia Laboratory diagnosis c. Brilliant Cresyl Blue Stain for Hb H induce precipitation of intrinsically unstable Hb H Hb H inclusion: denatured beta globin chain small, multiple, irregular shaped greenish blue bodies with pitted golf ball appearance (+): Hb H disease, α-thalassemia trait, silent α-thalassemia d. Acid Elution Slide Test for Hb F differentiate the intracellular distribution of Hb F in thalassemia (non-uniform) with increased Hb F in pancellular HPFP (uniform) Hb F: bright pink to red (infants) ”ghost cells”: only outer membrane is visible (adult)  Thank you ! ___END___ MCVG, RMT, MPH ”Nothing worth having comes easy, trust and enjoy the process.” References: Lotspeich-Steininger e.t al; Clinical hematology principles, procedures, correlations, Lippincott Company, 1992 Turgeon, Clinical Hematology: Theory and Procedures 5ht ed., Lippincott Williams & Wilkins, 2012 Keohane et. al, Rodak’s Hematology: Clincal Principles 6th ed., Elsevier, 2020