When do you have to perform the molecular biology in the hemoglobinopathies diagnosis
|
|
- Candice Bryan
- 6 years ago
- Views:
Transcription
1 When do you have to perform the molecular biology in the hemoglobinopathies diagnosis Maria Domenica Cappellini MD, FRCP;FACP Fondazione Ca Granda Policlinico IRCCS University of Milan
2 Disclosure Member of Advisory Board: - Novartis - Genzyme/Sanofi - Celgene - Shire - Merganser Biotech - Isis
3 Agenda Definition and patophysiology of Thalassemias Classification Hematological Diagnosis Molecular diagnosis
4 Classification of the thalassaemias Group of inherited haemoglobin disorders Absence or reduced synthesis of α chains of Hb α-thalassaemias Absence or reduced synthesis of β chains of Hb β-thalassaemias Muncie HL, Campbell JS. Am Fam Physician. 2009;80:
5 Globin genes cluster Chromosome 16 ζ α 2 α 1 Chromosome 11 ε Gγ Aγ δ β Embryonics: ζ 2 ε 2 Gower 1 ζ 2 γ 2 Portland α 2 ε 2 Gower 2 Fetals: α G o A 2 γ 2 HbF Adults α 2 β 2 HbA α 2 δ 2 HbA2
6 Globin synthesis at various stages of embryonic and fetal development Megaloblast Macrocyte Normocyte S ite of cell erythro-type poies is Liver Bone Marrow 50 Yolk sac α Spleen α 40 γ β ζ ε β δ γ B irth Post-conceptual age (weeks) Postnatal age (weeks)
7 Thalassemias are a group of inherited hemoglobinopathies Absence or reduced synthesis of α chains of Hb Absence or reduced synthesis of β chains of Hb α thalassemias 1 α thalassemia silent carrier (single α gene deletion) α thalassemia trait minor (double α gene deletion) Hb constant spring (reduced output of α globin) Hb H disease (triple α gene deletion) Hb Barts Hydrops (absence of α genes) 1. Muncie HL and Campbell JS. Am Fam Physician 2009;80: ; 2. Galanello R and Origa R. Orphanet J Rare Dis 2010;5:11. β thalassemias 2 β thalassemia minor (silent or carrier ) β thalassemia intermedia β thalassemia minor β thalassemia with Hb anomalies Hb C/β thalassemia Hb E/β thalassemia Hb S/β thalassemia Hereditary Hb F and β thalassemia β-thalassemia associated with Trichothiodystrophy X-linked thrombocytopenia
8 Thalassemia has a broad clinical spectrum, complicating diagnosis and management NTDT patients do not require regular red cell transfusions but may require occasional transfusions for growth failure, pregnancy, infections and other specific situations 1 4 NTDT β thalassemia intermedia Mild/moderate Hb E/β thalassemia Hb H disease (α thalassemia) Hb S β thalassemia Hb C thalassemia Transfusions seldom required Occasional transfusions required (eg surgery, pregnancy, infection) Intermittent transfusions required (eg poor growth and development, specific morbidities) Regular, lifelong transfusions required for survival Transfusions not required α thalassemia trait β thalassemia minor 1.Taher AT et al. Br J Haematol 2011;152: ; 2. Galanello R and Origa R. Orphanet Journal of Rare Diseases 2010;5:11; 3. Vichinsky E. Hematology Am Soc Hematol Educ Program 2007;79 83; 4. Muncie HL and Campbell JS. Am Fam Physician 2009;80: ; 5. Figure adapted from Musallam KM et al. Haematologica 2013;98: Transfusion-dependent thalassemia (TDT) β thalassemia major Severe Hb E/β thalassemia Hb Barts hydrops (α thalassemia major).
9 Agenda Definition and patophysiology of Thalassemias Classification Hematological Diagnosis Molecular analysis
10 Several assessments can assist diagnosis Family history Laboratory exams Diagnosis should incorporate as much information as possible, utilizing family history, and laboratory examinations 1. Taher A et al. Guidelines for the management of NTDT. 2013;TIF Publication No. 19; 2. Weatherall DJ. Blood Rev 2012;26S:S3 S6.
11 Diagnostic work-up of Thalassemias Primary hematology tests Full medical history Family history (screen families in high risk areas) Complete blood cell count with erythrocyte indices (use an automated blood cell counter) Blood smear/bcb staining + Low MCV (<80 fl) ± Low MCH (<27 pg) Microcytosis Hypochromia Target cells ± Inclusion bodies (Hb H) Serum ferritin >12 ng/ml _ Consider other causes of anemia Serum ferritin 12 ng/ml Consider iron deficiency anemia Adequate iron supplement for 3 months Screen for type of thalassemia Hb A 2 4% Hb F 0.1 5% Hb electrophoresis and HPLC Hb A 2 <4% Hb F <1% Hb A 2 4% Hb F >5 50% Hb H <5 25% Hb A 2 <4% ±Hb CS/PS No improvement + Other normal Hb variant Genetic testing β thalassemia trait α thalassemia traits and related disorders β thalassemia intermedia Hb H disease Hb E disorders Hb S disorders Hb C disorders Others DNA analysis for α and β globin mutations BCB, brilliant cresyl blue; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin Viprakasit V et al. Personal communication.
12 Formulas based on parameters from the CBC The most commonly used formulas are the following: Mentzer index (MI) = MCV/RBC Discriminant factor (DF) = MCV x (RDW/Hb 9 x100) Shine and Lal Index (S&L) = MCV x (MCH/100) Srivastava Index (SI) = MCH/RBC; RDW index (RDWI) = (MCV 9 RDW)/RBC Chatterjee T, Chakravarty A, Chakravarty S. Hemoglobin 2015;39:384 8.
13 HPLC and electrophoresis examples Hb electrophoresis of Hb H disease Vip Viprakasit. EHA Educational Book 2013.
14 Agenda Definition and patophysiology of Thalassemias Classification Hematological Diagnosis Molecular diagnosis
15 Diagnosis of NTDT is challenging due to the diversity of genotype interactions and limited understanding of the disease Weaker understanding of milder forms Diagnosis can be more difficult NTDT Excellent understanding of severe forms such as β thalassemia major Diagnosis is clear TDT Weaker Moderate Strong Early identification is key to ensure the most appropriate monitoring and treatment 1. Musallam KM. Haematologica 2013;98:
16 Several laboratory tests are available which together contribute to an NTDT diagnosis Hb levels Blood smear Other RBC findings HPLC electrophoresis DNA analysis (not always available) Diagnosis should incorporate as much information as possible, utilizing patient history, physical and laboratory examinations HPLC, high-performance liquid chromatography; RBC, red blood cells 1. Taher AT et al. Blood Cells Mol Dis 2006;37:12 20; 2. Galanello R and Origa R. Orphanet J Rare Dis 2010;5:11; 3. Harteveld C and Higgs D. Orphanet J Rare Dis 2010;5:13.
17 Laboratory examination: parameters that can help distinguish and diagnose different forms of NTDT β TI Hb E/β thalassemia Hb H Hb levels ~7 10 g/dl 1 Blood smear HPLC electrophoresis DNA analysis Basophilic stippling 6 Nucleated RBC 6 Hb F 10 50% (up to 100%) 5 Hb A 2 >4% 5 Genetic analysis should be performed in event of abnormal hematology findings 2 Mild 2 Moderately Severe 2 Severe g/dl 6 7 g/dl 4 5 g/dl Target cells 7 Red cell hypochromia 7 Microcytes 7 Nucleated RBC 7 hemolysis 4 Hb E and F 6 Hb A 2 9 To distinguish between different Hb E disorders g/dl 3 Microcytosis 8 Hypochromia 8 Target cells 8 Inclusion bodies 8 Irregularly crenated RBC 8 Increased reticulocytes (5 10%) 8 α/β-globin chain synthesis ratio measurement 3 RBC indices 3 Hb A 2 3 Variable Hb H (0.8 40%) and occasional Hb Barts hydrops 3 Gap-PCR developed for seven common α thalassemia 3 For unknown rearrangements, Southern Blotting or MLPA analysis required 3 MLPA, multiplex ligation-dependent probe amplification PCR, polymerase chain reaction 1. Taher AT et al. Blood Cells Mol Dis 2006;37:12 20; 2. Galanello R et al. Orphanet J Rare Dis 2010;5:11; 3. Harteveld C et al. Orphanet J Rare Dis 2010;5:13; 4.Vichinsky E. Hematology Am Soc Hematol Educ Program 2007;79 83; 5. Thalassaemia International Federation. Guidelines for the Clinical Management of thalassaemia, 2nd edition revised 2008; 6. Yaish HM et al Fucharoen S et al. Clin Chem 1998;44:
18 Globin Chain Synthesis Before the DNA era, the globin chain synthesis analysis,introduced more than 30 years ago, was utilized to identify the severity of globin chain Imbalance and consequently to predict the clinical severity. This method has been used in the late 1970s for prenatal diagnosis At present, it remains a sensitive diagnostic tool limited to define some complex or atypical forms of thalassemia.
19 Molecular Analysis The molecular diagnosis was applied in hemoglobinopathies and thalassemias an early stage of DNA era These diseases have been used as a prototype for the development of new techniques for molecular abnormalities. At present, there are many different PCR-based techniques used to diagnose the known globin gene mutations as well as other methods to identify the unknown mutations
20 Molecular Analysis There are more than 300 known b-thalassemia mutations, the majority being single nucleotide substitutions,insertions, or short deletions Fortunately, a limited number of point mutations are prevalent in different ethnic group; therefore, for any given ethnic region, a PCR method designed to detect the common-specific mutation simultaneously is initially used With this approach, more than 80% of cases for most ethnic groups could be identify.
21 Other Molecular Techniques Reverse-dot-blotting technique, in which amplified DNA is hybridized to a panel of mutation-specific probes fixed to a nylon strip The amplification refractory mutation system: It is rapid, cost-effective, and convenient to test multiple mutations simultaneously Denaturing gradient gel electrophoresis is an alternative approach to the above-mentioned methods, and it is convenient in countries where a very large spectrum of b-mutations occur
22 DNA sequencing The improvement and cost reduction of DNA sequencing rendered the direct sequence of b-gene the most widely use in many laboratories allowing the analysis of the exact nucleotide sequence of the gene or the gene area under evaluation The original method described by Sanger et al. in 1977 has been modified and today several type of automatic sequencer is available Direct sequencing allows also the identification of unknown mutation
23 Alpha Genes The amplification of sequences in the a -globin gene cluster is more difficult than that of the b-globin gene cluster due to a considerable sequence homology within the a-globin gene cluster. For the unknown a-deletion, the Southern blotting technique is still used in some laboratories More recently, the multiplex ligation dependent probe amplification have been introduced: sensitive, reproducible, no radioactivity need
24 Next-Generation Sequencing Next-generation sequencing (NGS) represents a new principle of sequencing technology; it increases the sequencing capacity from a few hundred base pairs to several thousands in a single analysis NGS is based on massively parallel sequencing of clonally amplified DNA molecules, coupled with sufficient computational power and appropriate software for efficient data analysis It has brought genetic diagnostics into clinical practice at an affordable price
25 Conclusions DNA analysis for globin gene mutations is not required to diagnose most of the carrier status It is advisable to confirm the diagnosis of TDT, knowing the parents mutations It is advisable in NTDT cases were the coinheritance of different globin gene defects may beresponsible for different phenotypes Some cases are hematologically and clinically difficult to be diagnosed even with the family hematological evaluations
26 J. (10 yrs) and E. (6 yrs) J. Transfusion dependent from the age of 6 yrs E. Occasional transfusions Hb: 8,6 g/dl J. E. Hb: 8.8 g/dl Father Hb: 12,8 g/dl Hb: 10,3 g/dl Mother MCV: 62,6 fl MCH: 20.3 pg MCV: 59,2 fl MCH: 19.3 pg HbA 2 : 4,8% HbA 2 : 5,10% HbF: 14,60% HbF: 13,10 % Anisocitosis ipochromia Anisocitosis anisochromia MCV: 63 fl MCH: 19,9 pg MCV: 72,8 fl MCH: 23,3 pg HbA 2 : n.d. HbA 2 : 3.1% HbF: n.d. HbF: 0,9 % Anisocitosi,s ipochromia Microcitosis and mild ipochromia
27 β Splicing mutation causing a premature stop codon Triplication ααα No functional protein IVSI-I heterozigosity HBB: c.[92+1g>a];[=] Triplication 3.7 ααα anti3.7 /αα IVSI-i heterozigosity HBB: c.[92+1g>a];[=] Triplication 3.7 ααα anti3.7 /αα Trans Allele of α3.7 deletion
28 Hb: 8,6 g/dl J. E. Hb: 8.8 g/dl Madre Hb: 10,3 g/dl Hb: 13,9 g/dl ααα/αα MCV: 62,6 fl MCH: 20.3 pg MCV: 59,2 fl MCH: 19.3 pg HbA 2 : 4,8% HbA 2 : 5,10% HbF: 14,60% HbF: 13,10 % Anisocitosis ipocrhomia Anisocitosis anisochromia MCV: 72,8 fl MCV: 80 MCH: 23,3 pg MCH: 28 HbA 2 : 3.1% HbA 2 : 2,4% HbF: 0,9 % HbF: 0,8% Microcitosis and emild ipochromia n.a. Something not clear with the mum
29 MLPA Multiplex-Ligation Probe-dependent Amplification Identification of chnges in copy number deletion ) (duplication and
30
31
32 MLPA CLUSTER ALFA GLOBINICO Quadruplication of alpha genes αααα/αα α 2 α 2 α 2 α 1 /α 2 α 1 α 2 α 1 2 α 1 2 α 1 /α 2 α 1
33
34 Quadruplication alpha αααα/αα αα/αα quadruplication αααα/αα IVSI-I in eterozigosi HBB: c.[92+1g>a];[=] Triplication+ Quadruplication αααα/ααα IVSI-I in eterozigosi HBB: c.[92+1g>a];[=] Triplication+Quadruplication αααα/ααα
35 Principles of prenatal diagnosis: molecular approach Mutated alleles in both parents must be identified before prenatal testing can be performed Prenatal diagnosis for pregnancies at increased risk could be done through: chorionic villi sampling at around 11 weeks' gestation analysis of DNA extracted from fetal cells obtained by amniocentesis, usually performed at approximately weeks' gestation 1. McPhee J. Science Creative Quarterly. 2011;6. Available from: Accessed March
36 Centro Anemie Congenite e Medicina Interna 1A Policlinico di Milano Maria.cappellini@unimi.it
MICO Maggio 2016 Laboratory Diagnosis of Thalassemia
MICO 11-15 Maggio 2016 Laboratory Diagnosis of Thalassemia Maria Domenica Cappellini Fondazione Ca Granda Policlinico IRCCS University of Milan Disclosure Member of Advisory Board: - Novartis - Genzyme/Sanofi
More informationDiagnostic difficulties in prevention and control program for thalassemia in Thailand: atypical thalassemia carriers
Diagnostic difficulties in prevention and control program for thalassemia in Thailand: atypical thalassemia carriers Pranee Winichagoon Fucharoen Thalassemia Research Center Institute of Molecular Biosciences
More informationCorporate Medical Policy
Corporate Medical Policy Genetic Testing for Alpha Thalassemia File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_testing_for_alpha_thalassemia 9/2013 7/2017 7/2018 7/2017 Description
More informationBeta-thalassemia:clinical findings,molecular defects and genotype/phenotype relationships
Beta-thalassemia:clinical findings,molecular defects and genotype/phenotype relationships Maria Domenica Cappellini Fondazione Ca Granda Policlinico IRCCS University of Milan Disclosure Member of Advisory
More informationIn adults, the predominant Hb (HbA) molecule has four chains: two α and two β chains. In thalassemias, the synthesis of either the α or the β chains
Thalassaemias Thalassemia Thalassemia is an inherited autosomal recessive blood disease. Associated with absence or reduction in a or b globin chains. Reduced synthesis of one of the globin chains can
More informationLe Emoglobinopa4e. Le Anemie Congenite del Migrante. Maria Domenica Cappellini Fondazione Ca Granda Policlinico Università di Milano
Le Anemie Congenite del Migrante Le Emoglobinopa4e Maria Domenica Cappellini Fondazione Ca Granda Policlinico Università di Milano Ravenna 25 marzo 2017 Emoglobinopatie Sindromi Talassemiche: - TDT - NTDT
More informationHematologic Features of Alpha Thalassemia Carriers
IJMCM Summer 2012, Vol 1, No 3 Original Article Hematologic Features of Alpha Thalassemia Carriers Haleh Akhavan-Niaki 1,2, Reza Youssefi Kamangari 2, Ali Banihashemi 2, Vahid Kholghi Oskooei 1, Mandana
More informationThalassemias. Emanuela Veras, M.D. 01/08/2006
Thalassemias Emanuela Veras, M.D. 01/08/2006 Structure and Function of normal Hemoglobin molecules: 2/3 1/3 β: increases from 6 th week of fetal life to 12 months of age At birth: HbF: 75-90% HbA: 10-25%
More informationReport of Beta Thalassemia in Newar Ethnicity
Report of Beta Thalassemia in Newar Ethnicity Rajendra Dev Bhatt 1*, Surendra Koju 2, Prabodh Risal 1 Affiliations: 1 Department of Clinical Biochemistry, Dhulikhel Hospital, Kathmandu University Hospital
More informationThalassemias:general aspects and molecular pathology
Thalassemias:general aspects and molecular pathology Prof. Renzo Galanello Pediatric Clinic 2 University of Cagliari Ospedale Regionale Microcitemie-ASL8 HEMOGLOBINOPATHIES CLASSIFICATION Structurally
More informationLine Probe Assay for Detection of Alpha Thalassemia: A Pilot Study
Line Probe Assay for Detection of Alpha Thalassemia: A Pilot Study Menon PK *, Nimmakayalu M, Bylappa SK, Kumar M, Abdalhaleem HM Center for Advanced Biomedical Research and Innovation, Gulf Medical University,
More informationDr.Abdolreza Afrasiabi
Dr.Abdolreza Afrasiabi Thalassemia & Heamophilia Genetic Reaserch Center Shiraz Medical University Hemoglobin tetramer Hemoglobin Structure % A 1 α 2 β 2 94-97% A 2 α 2 δ 2 2.5% A 1C α 2 (β-n-glucose)
More informationAnemia s. Troy Lund MSMS PhD MD
Anemia s Troy Lund MSMS PhD MD lundx072@umn.edu Hemoglobinopathy/Anemia IOM take home points. 1. How do we identify the condtion? Smear, CBC Solubility Test (SCD) 2. How does it present clincally? 3. How
More informationHAEMOGLOBINOPATHIES. Editing file. References: 436 girls & boys slides 435 teamwork slides. Color code: Important. Extra.
HAEMOGLOBINOPATHIES Objectives: normal structure and function of haemoglobin. how the globin components of haemoglobin change during development, and postnatally. the mechanisms by which the thalassaemias
More informationNext Generation Sequencing as a tool for breakpoint analysis in rearrangements of the globin-gene clusters
Next Generation Sequencing as a tool for breakpoint analysis in rearrangements of the globin-gene clusters XXXth International Symposium on Technical Innovations in Laboratory Hematology Honolulu, Hawaii
More informationHaemoglobinopathies case studies 11 th Annual Sickle Cell and Thalassaemia Conference October 2017
Haemoglobinopathies case studies 11 th Annual Sickle Cell and Thalassaemia Conference 11 13 October 2017 Chris Lambert Haematology Service Delivery Manager Viapath Laboratories Kings College Hospital HUMAN
More informationMOLECULAR BASIS OF THALASSEMIA IN SLOVENIA
MOLECULAR BASIS OF THALASSEMIA IN SLOVENIA Dijana Plaseska-Karanfilska, MD, PhD Research Centre for Genetic Engineering and Biotechnology Georgi D. Efremov, Macedonian Academy of Sciences and Arts, Skopje,
More informationLaboratory diagnosis of thalassemia
International Journal of Laboratory Hematology REVIEW ARTICLE The Official journal of the International Society for Laboratory Hematology INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY Laboratory diagnosis
More informationGenetics of Thalassemia
Genetics of Thalassemia Submitted by : Raya Samir Al- Hayaly Sura Zuhair Salih Saad Ghassan Al- Dulaimy Saad Farouq Kassir Sama Naal Salouha Zahraa Jasim Al- Aarajy Supervised by : Dr. Kawkab Adris Mahmod
More informationComprehensive Hemoglobin Analysis HBA1/2 (
Comprehensive Hemoglobin Analysis HBA1/2 ( α-globin) and HBB (β-globin) mutation and deletion/duplication analysis and HBD (δ-globin) and HBG1/2 (γ-globin) mutation analysis Description: Hemoglobin (Hb)
More informationRed Cell Indices and Functions Differentiating Patients with the β-thalassaemia Trait from those with Iron Deficiency Anaemia
The Journal of International Medical Research 2009; 37: 25 30 [first published online as 37(1) 4] Red Cell Indices and Functions Differentiating Patients with the β-thalassaemia Trait from those with Iron
More informationThalassemia intermedia in HbH-CS disease with compound heterozygosity for β-thalassemia: Challenges in hemoglobin analysis and clinical diagnosis
Genes Genet. Syst. (2009) 84, p. 67 71 Thalassemia intermedia in HbH-CS disease with compound heterozygosity for β-thalassemia: Challenges in hemoglobin analysis and clinical diagnosis Jin Ai Mary Anne
More information6.1 Extended family screening
CHAPTER 6 CONCLUSION Cost benefit analysis of thalassemia screening programs have shown that the single years treatment for a β-thalassemia major patient was much higher than a total cost per case prevented.
More informationThe Thalassemias in Clinical Practice. Ashutosh Lal, MD Director Comprehensive Thalassemia Program UCSF Benioff Children s Hospital Oakland
The Thalassemias in Clinical Practice Ashutosh Lal, MD Director Comprehensive Thalassemia Program UCSF Benioff Children s Hospital Oakland Outline Thalassemia: definitions and pathophysiology Epidemiology
More informationPOLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER CODING INFORMATION REFERENCES POLICY HISTORY
Original Issue Date (Created): November 26, 2013 Most Recent Review Date (Revised): November 26, 2013 Effective Date: April 1, 2014 POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS
More informationScreening for haemoglobinopathies in pregnancy
Policy Statement All Southern Health patients will receive clinical care that reflects best practice and is based on the best available evidence. Index of chapters within background 1. Prevalence of haemoglobinopathies
More informationThalassemia Maria Luz Uy del Rosario, M.D.
Thalassemia Maria Luz Uy del Rosario, M.D. Philippine Society of Hematology and Blood Transfusion Philippine Society of Pediatric Oncology What is Thalassemia Hereditary Hemoglobin disorder Hemolytic anemia
More informationPrevalence of Thalassemia in Patients With Microcytosis Referred for Hemoglobinopathy Investigation in Ontario A Prospective Cohort Study
Hematopathology / PREVALENCE OF THALASSEMIA IN ONTARIO Prevalence of Thalassemia in Patients With Microcytosis Referred for Hemoglobinopathy Investigation in Ontario A Prospective Cohort Study John D.
More informationMedical Policy. MP Genetic Testing for α-thalassemia. Related Policies Preimplantation Genetic Testing
Medical Policy BCBSA Ref. Policy: 2.04.104 Last Review: 02/26/2018 Effective Date: 02/26/2018 Section: Medicine Related Policies 4.02.05 Preimplantation Genetic Testing DISCLAIMER Our medical policies
More informationEmoglobinopatie frequenti e meno frequenti
Highlights in Ematologia Treviso, 17-18 Novembre 2017 Emoglobinopatie frequenti e meno frequenti Elena Cassinerio Centro Malattie Rare Fondazione IRCCS Cà Granda Ospedale Maggiore Milano Conflitto d interesse
More informationGenetic Testing for α-thalassemia
Medical Policy Manual Genetic Testing, Policy No. 52 Genetic Testing for α-thalassemia Next Review: January 2019 Last Review: January 2018 Effective: February 1, 2018 IMPORTANT REMINDER Medical Policies
More informationPitfalls in the premarital testing for thalassaemia
Pitfalls in the premarital testing for thalassaemia Dr. Riad Amer MB ChB, MSc, FRCP, FRCPath, JBH Assistant Professor of Medicine Al Najah University Consultant Haematologist Case 1 Husband and Wife are
More informationHaematological and Genetic Characterization of Thalassemia Intermedia in Tank and South Waziristan Agency of Khyber Pakhtun Khwa
Journal of Health Science 2017, 7(3): 39-43 DOI: 10.5923/j.health.20170703.01 Haematological and Genetic Characterization of Thalassemia Intermedia in Tank and South Waziristan Agency of Khyber Pakhtun
More informationThe influence of sickle cell and beta thalassaemia traits on type 2 diabetes mellitus
Diabetes Management The influence of sickle cell and beta thalassaemia traits on type 2 diabetes mellitus Taiwo R Kotila *1, Jokotade O Adeleye 2, Mabel A Charles-Davies 3, Funmilola A Mapayi 3, Matthew
More informationCurrent Topics in Hemoglobinopathies
Current Topics in Hemoglobinopathies Bruce R Haas, MS, LCGC 28-29 September 2015 bruce.r.haas@kp.org 1 How malaria escapes effective immunological responses P falciparum exports PfEMP1 proteins and concentrate
More informationClinical Characteristics of Pediatric Thalassemia in Korea: A Single Institute Experience
ORIGINAL ARTICLE Pediatrics http://dx.doi.org/10.3346/jkms.2013.28.11.1645 J Korean Med Sci 2013; 28: 1645-1649 Clinical Characteristics of Pediatric Thalassemia in Korea: A Single Institute Experience
More informationHEMOGLOBIN ELECTROPHORESIS DR ARASH ALGHASI SHAFA HOSPITAL-AHWAZ
HEMOGLOBIN ELECTROPHORESIS DR ARASH ALGHASI SHAFA HOSPITAL-AHWAZ Hemoglobin Hemoglobin (Hb), protein constituting 1/3 of the red blood cells Each red cell has 640 million molecules of Hb sites in the cells:
More informationWhat is Thalassaemia?
What is Thalassaemia? Introduction The thalassaemias are a diverse group of genetic blood diseases characterized by absent or decreased production of normal hemoglobin, resulting in a microcytic anemia
More informationDr Banu Kaya Consultant Haematologist Barts Health NHS Trust Royal London Hospital, London, UK SICKLE CELL AND THALASSAEMIA OVERVIEW
Dr Banu Kaya Consultant Haematologist Barts Health NHS Trust Royal London Hospital, London, UK SICKLE CELL AND THALASSAEMIA OVERVIEW Objectives Gain awareness of haemoglobinopathy inheritance, pathophysiology
More informationThe diagnosis of Hemoglobinopathies
1ST IFCC, EFLM, AFCB CONFERENCE "LABORATORY MEDICINE: MEETING THE NEEDS OF MEDITERRANEAN NATIONS" Rome, Italy 02/07/2018 The diagnosis of Hemoglobinopathies Dr Antonino Giambona Unit of Hematology of Rare
More informationUnraveling Hemoglobinopathies with Capillary Electrophoresis
Session Number 2002 Unraveling Hemoglobinopathies with Capillary Electrophoresis David F. Keren, M.D. Professor of Pathology Division Director, Clinical Pathology The University of Michigan dkeren@med.umich.edu
More informationEducational Items Section
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Educational Items Section Hemoglobin genes; Sickle-cell anemia - Thalassemias Jean-Loup Huret, Xavier Troussard
More informationHaemoglobin BY: MUHAMMAD RADWAN WISSAM MUHAMMAD
Haemoglobin BY: MUHAMMAD RADWAN WISSAM MUHAMMAD Introduction is the iron-containing oxygen transport metalloprotein in the red blood cells Hemoglobin in the blood carries oxygen from the respiratory organs
More informationUse of mathematical indices based on CBC data to identify patients with β thalassemia minor
Revista Română de Medicină de Laborator Vol. 8, Nr. 3, Septembrie 27 7 Use of mathematical indices based on CBC data to identify patients with β thalassemia minor Trefor Higgins *, Yann Brierley 2, Annu
More informationAnaemia in Pregnancy
Anaemia in Pregnancy Definition :anaemia is a pathological condition in which the oxygen-carrying capacity of red blood cells is insufficient to meet the body needs. The WHO : haemoglobin concentration
More informationManagement of extramedullary hematopoiesis in pa5ents with thalassemia
Management of extramedullary hematopoiesis in pa5ents with thalassemia Maria Domenica Cappellini Fondazione Ca Granda Policlinico IRCCS University of Milan Disclosure Member of Advisory Board: - Novar4s
More informationNational Haemoglobinopathy Reference Laboratory. Information for Users
National Haemoglobinopathy Reference Laboratory Information for Users Summary The NHRL offers a service for the identification of haemoglobinopathy genotypes by the molecular analysis of DNA and haematological
More informationBlood Cells, Molecules and Diseases
Blood Cells, Molecules and Diseases 50 (2013) 93 98 Contents lists available at SciVerse ScienceDirect Blood Cells, Molecules and Diseases journal homepage: www.elsevier.com/locate/bcmd Alpha Thalassaemia
More informationMicrocytic Hypochromic Anemia An Approach to Diagnosis
Microcytic Hypochromic Anemia An Approach to Diagnosis Decreased hemoglobin synthesis gives rise to microcytic hypochromic anemias. Hypochromic anemias are characterized by normal cellular proliferation
More informationCLINICAL AND HEMATOLOGICAL PHENOTYPE OF HOMOZYGOUS HEMOGLOBIN E: REVISIT OF A BENIGN CONDITION WITH HIDDEN REPRODUCTIVE RISK
CLINICAL AND HEMATOLOGICAL PHENOTYPE OF HOMOZYGOUS HEMOGLOBIN E: REVISIT OF A BENIGN CONDITION WITH HIDDEN REPRODUCTIVE RISK Kalaya Tachavanich, Vip Viprakasit, Worawut Chinchang, Waraporn Glomglao, Parichat
More informationResearch Article Clinical Features and Molecular Analysis of Hb H Disease in Taiwan
BioMed Research International, Article ID 271070, 5 pages http://dx.doi.org/10.1155/2014/271070 Research Article Clinical Features and Molecular Analysis of Hb H Disease in Taiwan Yu-Hua Chao, 1,2,3 Kang-Hsi
More informationHEMOLYTIC ANEMIA DUE TO ABNORMAL HEMOGLOBIN SYNTHESIS
Hemolytic Anemia Due to Abnormal Hemoglobin Synthesis MODULE 19 HEMOLYTIC ANEMIA DUE TO ABNORMAL HEMOGLOBIN SYNTHESIS 19.1 INTRODUCTION There are two main mechanisms by which anaemia is produced (a) Thalassemia:
More informationHi & Ha, are new indices in differentiation between Iron deficiency anemia and beta-thalassaemia trait /A Study in Sulaimani City-Kurdistan/Iraq
IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-issn: 2279-0853, p-issn: 2279-0861.Volume 14, Issue 7 Ver. I (July. 2015), PP 67-72 www.iosrjournals.org Hi & Ha, are new indices in differentiation
More informationLaboratory for diagnosis of THALASSEMIA
SCBM343 CLINICAL PATHOLOGY 2(1-2-3) Laboratory for diagnosis of THALASSEMIA PORNTHIP CHAICHOMPOO pornthip.chh@mahidol.ac.th Acknowledgements Dr. Pranee Winichagoon Fucharoen Ms. Pornnapa Khampan Thalassemia
More informationHematopathology / SCREENING FOR THE (-- SEA ) ALPHA 0 -THALASSEMIA DELETION
Hematopathology / SCREENING FOR THE (-- SEA ) ALPHA 0 -THALASSEMIA DELETION A Reliable Screening Test to Identify Adult Carriers of the (-- SEA ) alpha 0 -Thalassemia Deletion Detection of Embryonic zeta-globin
More informationDetecting and Reporting Alpha Thalassemia In Newborns
Detecting and Reporting Alpha Thalassemia In Newborns T. Davis, C. Moore, L. Nayak, M.C. Dorley, M. del Pilar Aguinaga, M. Chan, J. Ubaike, C. Yusuf Alpha Thalassemia Screening Status in the US Clinical
More informationIRON2009_CAP.10( ):EBMT :24 Pagina 250 CHAPTER 10. Molecular basis of thalassaemia syndromes. Bill Wood, Doug Higgs
IRON2009_CAP.10(250-263):EBMT2008 4-12-2009 16:24 Pagina 250 * CHAPTER 10 Molecular basis of thalassaemia syndromes Bill Wood, Doug Higgs IRON2009_CAP.10(250-263):EBMT2008 4-12-2009 16:24 Pagina 251 CHAPTER
More informationJMSCR Vol 04 Issue 12 Pages December 2016
causes of microcytic hypochromic anemia. Sideroblastic anemia and lead intoxication are relatively uncommon. While the diagnosis of beta thalassemia major is usually becomes obvious within initial years
More informationHaemoglobin Lepore in a Malay family: a case report
Malaysian J Pathol 2005; 27(1) : 33 37 HAEMOGLOBIN LEPORE CASE REPORT Haemoglobin Lepore in a Malay family: a case report Josephine PASANGNA MPath, *Elizabeth GEORGE FRCPA, FRCPE and Menaka NAGARATNAM
More informationHematology Unit Lab 1 Review Material
Hematology Unit Lab 1 Review Material - 2018 Objectives Laboratory instructors: 1. Assist students during lab session Students: 1. Review the introductory material 2. Study the case histories provided
More informationSICKLE CELL DISEASE. Dr. MUBARAK ABDELRAHMAN MD PEDIATRICS AND CHILD HEALTH. Assistant Professor FACULTY OF MEDICINE -JAZAN
SICKLE CELL DISEASE Dr. MUBARAK ABDELRAHMAN MD PEDIATRICS AND CHILD HEALTH Assistant Professor FACULTY OF MEDICINE -JAZAN Objective: The student should be able: To identify the presentation, diagnosis,
More informationTransfusion support in Thalassaemia. Dr.A.keerti 1 st year PG DEPT. OF TRANSFUSION MEDICINE
Transfusion support in Thalassaemia Dr.A.keerti 1 st year PG DEPT. OF TRANSFUSION MEDICINE Structure of hemoglobin Types of hemoglobins Hemoglobin-Development Switching Thalassaemia- introduction Classification
More informationAn overview of Thalassaemias and Complications
An overview of Thalassaemias and Complications Haemoglobin Haemoglobin is the most abundant protein in blood, and exists as three main types in normal adults: HbA ( ) - 97% HbA 2 ( ) - 2.5% HbF ( ) - 0.5%
More informationHAEMATOLOGICAL EVALUATION OF ANEMIA. Sitalakshmi S Professor and Head Department of Clinical Pathology St John s medical College, Bangalore
HAEMATOLOGICAL EVALUATION OF ANEMIA Sitalakshmi S Professor and Head Department of Clinical Pathology St John s medical College, Bangalore Learning Objectives Laboratory tests for the evaluation of anemia
More informationPart I. Pathophysiology and management of Thalassemia Intermedia. M. Domenica Cappellini Fondazione IRCCS Policlinico University of Milan
Pathophysiology and management of Thalassemia Intermedia M. Domenica Cappellini Fondazione IRCCS Policlinico University of Milan 4th European Symposium on Rare Anaemias 3rd Bulgarian Symposium on Thalassaemia
More informationBRITISH BIOMEDICAL BULLETIN
Journal Home Page www.bbbulletin.org BRITISH BIOMEDICAL BULLETIN Original A Long Term Screening of Iranian Populations with Thalassemia and Hemoglobinopathies Soudabeh Hosseini 1,2, Ebrahim Kalantar 3,2
More informationHeme Questions and Derivatives for the USMLE Step One Exam. Winter Storm Skylar Edition
Heme Questions and Derivatives for the USMLE Step One Exam Winter Storm Skylar Edition Howard J. Sachs, MD Howard@12DaysinMarch.com www.12daysinmarch.com Patient presents for routine preoperative evaluation
More informationChanges in hematological parameters in α-thalassemia individuals co-inherited with erythroid Krüppel-like factor mutations
Clin Genet 2015: 88: 56 61 Printed in Singapore. All rights reserved Short Report 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd CLINICAL GENETICS doi: 10.1111/cge.12443 Changes in hematological
More informationMolecular Diagnosis of Thalassemias and Hemoglobinopathies. An ACLPS Critical Review CME/SAM. Daniel E. Sabath, MD, PhD ABSTRACT.
Molecular Diagnosis of Thalassemias and Hemoglobinopathies An ACLPS Critical Review Daniel E. Sabath, MD, PhD From the Department of Laboratory Medicine, University of Washington, Seattle. CME/SAM Key
More informationGeneral insights and current management of Thalassemia Intermedia. Maria Domenica Cappellini
Palermo 16 Settembre 217 General insights and current management of Thalassemia Intermedia Maria Domenica Cappellini Rare Disease Center Dept of Internal Medicine Fondazione IRCCS Cà Granda Policlinico
More informationNon-transfusion-dependent thalassemia (NTDT) Bor-Sheng Ko, M.D. Ph.D. Meng-Yao Lu, M.D. National Taiwan University Hospital
Non-transfusion-dependent thalassemia (NTDT) Bor-Sheng Ko, M.D. Ph.D. Meng-Yao Lu, M.D. National Taiwan University Hospital Introduction Spectrum of thalassemia: Resulting from unbalanced α/β chains α-thalassemias
More informationdb-thalassemia Patients With Homozygous Xmn-1 Polymorphism That Are Characterized By A Milder Phenotype
ISPUB.COM The Internet Journal of Hematology Volume 7 Number 2 db-thalassemia Patients With Homozygous Xmn-1 Polymorphism That Are Characterized By A Milder S Ashraf Citation S Ashraf. db-thalassemia Patients
More informationOrignal Article. Neeraja Pethe, Anil Munemane*, Suryakant Dongre ABSTRACT
Orignal Article Determination of Frequency of Thalassaemia Trait in a Rural Tertiary Care Hospital of India by Using Various Red Cell Indices as Screening Tool Neeraja Pethe, Anil Munemane*, Suryakant
More informationby Capillary Electrophoresis for Diagnosing β-thalassemia/ HbE Disease in Patients With Low HbF
Measurement of HbA by Capillary Electrophoresis for Diagnosing β-thalassemia/ HbE Disease in Patients With Low HbF Watcharee Prasing, BSc, 1 Sakorn Pornprasert, PhD 1 * Lab Med Summer 1;5:-3 DOI: 1.139/LMGD9HES3DZRBZM
More informationHemoglobinopathy. Pathophysiology of β Thalassemia A Guide to Molecular Therapies. Swee Lay Thein
Hemoglobinopathy Session Chair: George Stamatoyannopoulos, MD, DrSci Speakers: Swee Lay Thein, MD, FRCP, FRCPath, DrSci; Susan P. Perrine, MD; and Philippe Leboulch, MD Pathophysiology of β Thalassemia
More informationSusan Stegman, MD Medical Director AXA Equitable Life May 3, 2016
Susan Stegman, MD Medical Director AXA Equitable Life May 3, 2016 Underwriting impact Anemia overview Classification of anemia Specific anemia topics Iron deficiency anemia Thalassemia Megaloblastic anemia
More informationDr. Ayman Mohsen Mashi, MBBS Consultant Hematology & Blood Transfusion Department Head, Laboratory & Blood Bank King Fahad Central Hospital, Gazan,
Dr. Ayman Mohsen Mashi, MBBS Consultant Hematology & Blood Transfusion Department Head, Laboratory & Blood Bank King Fahad Central Hospital, Gazan, KSA amashi@moh.gov.sa 24/02/2018 β-thalassemia syndromes
More informationHaemoglobinopathy Case Studies. Dr Jill Finlayson Department of Haematology Pathwest Laboratory Medicine
Haemoglobinopathy Case Studies Dr Jill Finlayson Department of Haematology Pathwest Laboratory Medicine Case 1 KB, 36y M Refugee Afghanistan Screening bloods Hb 101 g/l RCC 3.75 x10 12 /L MCV 90 fl MCH
More informationRed cell disorder. Dr. Ahmed Hasan
Red cell disorder Dr. Ahmed Hasan Things to be learned in this lecture Definition and clinical feature of anemia. Classification of anemia. Know some details of microcytic anemia Question of the lecture:
More informationHow to Write a Life Care Plan for a Child with Hemoglobinopathy
How to Write a Life Care Plan for a Child with Hemoglobinopathy Tamar Fleischer, BSN, MSN, CNLCP & Mona Yudkoff, RN, MPH, CRRN, CNLCP BalaCare Solutions March 2018 St. Peterburg, Florida What is Hemoglobinopathy?
More informationMultidisciplinary care. Michael Angastiniotis
Multidisciplinary care Michael Angastiniotis Pathopysiology of β-thalassaemia Thalassaemia syndromes are inherited haemoglobin disorders caused by defective and imbalanced globin production Excess free
More informationBMC Research Notes. Open Access CASE REPORT
DOI 10.1186/s13104-016-2027-1 BMC Research Notes CASE REPORT Open Access Combination of a triple alpha globin gene with beta thalassemia in a gypsy family: importance of the genetic testing in the diagnosis
More informationEpidemiological Study among Thalassemia Intermedia Pediatric Patients
Med. J. Cairo Univ., Vol. 78, No. 2, December 651-655, 2010 www.medicaljournalofcairouniversity.com Epidemiological Study among Thalassemia Intermedia Pediatric Patients NERMEEN KADDAH, M.D.; KHALED SALAMA,
More informationDr B Lal Clinical Laboratory Pvt Ltd. Jaipur, Rajasthan, India
Volume 1, Issue 1, pp: 1-5 Research Article Introduction Open Access Role of Hematological Indices in the Screening of Β-Thalassemia Minor (Trait) and Iron Deficiency Shaily Garg, Anshika Srivastava, Sanjeev
More informationClinical, haematological, and genetic studies of type 2
Journal of Medical Genetics 1988, 25, 195-199 Clinical, haematological, and genetic studies of type 2 normal Hb A2 thalassaemia ANNA METAXOTOU-MAVROMATI, CHRISTOS KATTAMIS, LILIAN MATATHIA, MARIA TZETIS,
More informationHigh Hemoglobin F in a Saudi Child Presenting with Pancytopenia
Case Report imedpub Journals http://www.imedpub.com Journal of Pediatric Care ISSN 2471-805X DOI: 10.21767/2471-805X.100002 High Hemoglobin F in a Saudi Child Presenting with Pancytopenia Abstract Saudi
More information4 Jumana Jihad Dr. Ahmad Mansour Dr. Ahmad Mansour
4 Jumana Jihad Dr. Ahmad Mansour Dr. Ahmad Mansour Anemia Decreased blood production Increased blood loss Hemolytic Hemorrhage Extravascular Intravascular Hemolytic (Further classification( Extrinsic Intrinsic
More informationBeta thalassaemia traits in Nigerian patients with sickle cell anaemia
JMBR: A Peer-review Journal of Biomedical Sciences June 2005 Vol. 4 No.1 pp-37-43 Beta thalassaemia traits in Nigerian patients with sickle cell anaemia CE Omoti ABSTRACT Haematological values were determined
More informationCounselling and prenatal diagnosis. Antonis Kattamis, Greece
Counselling and prenatal diagnosis Antonis Kattamis, Greece Epidemiology of Hemoglobinopathies 7% of world population carriers of hemoglobinopathies 500.000 newborns annually affected 300.000 : Thalassemias
More informationDEVELOPMENT OF A HAEMOGLOBINOPATHY GENETIC DIAGNOSTIC SERVICE FOR THE NORTH WEST OF ENGLAND
DEVELOPMENT OF A HAEMOGLOBINOPATHY GENETIC DIAGNOSTIC SERVICE FOR THE NORTH WEST OF ENGLAND A thesis submitted to the Manchester Metropolitan University for the degree of Master of Philosophy in the Faculty
More informationQuiz. What percentage of the world s population is a carrier of a hemoglobinopathy? Hemoglobinopathies in Pregnancy 1-2% 5-7% 8-12% 10-15%
Hemoglobinopathies in Pregnancy Emily Parkhurst, MS, LCGC Kaiser West Los Angeles November 2017 Genetics Department Quiz What percentage of the world s population is a carrier of a hemoglobinopathy? 1-2%
More informationA Reliable Screening Protocol for Thalassemia and Hemoglobinopathies in Pregnancy An Alternative Approach to Electronic Blood Cell Counting
Hematopathology / SCREENING FOR THALASSEMIA AND HEMOGLOBINOPATHIES IN PREGNANCY A Reliable Screening Protocol for Thalassemia and Hemoglobinopathies in Pregnancy An Alternative Approach to Electronic Blood
More informationHemolytic anemias (2 of 2)
Hemolytic anemias (2 of 2) Sickle Cell Anemia The most common familial hemolytic anemia in the world Sickle cell anemia is the prototypical (and most prevalent) hemoglobinopathy Mutation in the β-globin
More informationNuovi strumenti diagnostici : NGS era
Nuovi strumenti diagnostici : NGS era Achille Iolascon, MD, PhD Dept. Molecular Medicine and Medical Biotechnology, University Federico II, Naples, Italy achille.iolascon@unina.it madre padre figlio neonato
More informationThe Beats of Natural Sciences Issue 3-4 (September-December) Vol. 3 (2016)
Frequency of β (Beta Thalassaemia) Trait and Haemaglobin E (HbE) Trait: Case Study in a Thalassaemia Carrier Detection Camp in Gurudas College, West Bengal, India Mitu De Department of Botany, Gurudas
More informationS-Beta Thalassemia leading to avascular necrosis of left hip joint in a young male - A rare case report
Case Report S-Beta Thalassemia leading to avascular necrosis of left hip joint in a young male - A rare case report Shubhi Saxena 1*, Nishant Saxena 1, R.M Jaiswal 2 1 PG Student, 2 Associate Professor,
More informationCover Page. The handle holds various files of this Leiden University dissertation.
Cover Page The handle http://hdl.handle.net/1887/35456 holds various files of this Leiden University dissertation. Author: Hassan, Suha Mustafa Title: Toward prevention of Hemoglobinopathies in Oman Issue
More informationNew technologies for the diagnosis of thalassemia:
New technologies for the diagnosis of thalassemia: Cornelis Harteveld Leiden University Medical Center, The Netherlands ENERCA Ferrara 16 th of November 2013 Introduction to hemoglobinopathies Hb molecule
More informationijifm case report ABSTRACT
ijifm case report 1p36 Deletions 10.5005/jp-journals-10016-1085 in Two Cases with Thalassemia 1p36 Deletions in Two Cases with Thalassemia 1 Puspal De, 2 Sudipa Chakravarty, 3 Amit Chakravarty ABSTRACT
More information