DOCSLIB.ORG

Inherited Bleeding Disorders in Obstetrics and Gynaecology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Inherited Bleeding Disorders in Obstetrics and Gynaecology MEUluAL LIBHAHY ROYAL FREE HOSPITAL HAMPSTEAD INHERITED BLEEDING DISORDERS IN OBSTETRICS AND GYNAECOLOGY Rezan A Abdul-Kadir, MB ChB, FRCS(Ed), MRCOG Submitted for the Doctor of Medicine Degree Royal Free and University College Medical School London (ACCESSION | NUMBER O&RLy ProQuest Number: 10797831 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 10797831 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 2 ABSTRACT The aim of this thesis is to investigate the obstetric and gynaecological problems and their management in women with inherited bleeding disorders, as well as the role of such disorders in obstetric and gynaecological haemorrhage. The uptake of prenatal diagnosis and termination of an affected pregnancy is low in carriers of haemophilia. Fetal gender determination has important implications in the management of labour in carriers who do not wish to have specific prenatal diagnosis. The attitude of women towards reproductive choices is influenced by ethnic and cultural issues and family experience with the disease. Haemostatic response to pregnancy is variable in different types and subtypes of inherited bleeding disorders and in the same patient in different pregnancies. Haemorrhagic complications are confined to post-abortal and post-partum period. The incidence of primary and secondary post-partum haemorrhage was 22% and 11% in carriers of haemophilia, 18.5% and 20% in vWD and 16% and 24% in FXI deficient women, respectively. Women with low factor levels (< 50 iu/dl) and no prophylactic treatment for labour and puerperium are especially at risk. There are great inter- and intra-individual variations in coagulation markers in women due to different physiological conditions including age, ethnicity, blood group and hormonal changes during different phases of the menstrual cycle. ^ u u ' 3 Women with inherited bleeding disorders suffer from heavy and prolonged menstruation which adversely affects their quality of life. Objectively confirmed menorrhagia is significantly higher in these women (67%) compared with the control group (29%). On the other hand, undiagnosed inherited bleeding disorders can be the underlying cause in a significant proportion (17%) of women presenting with unexplained menorrhagia. The DDAVP nasal spray was shown not to be superior to placebo in the treatment of menorrhagia. Increased awareness among clinicians responsible for women’s health of these disorders and their morbidity and the availability of management guidelines are essential for optimal care and improvement of the quality of life of these patients. 4 CONTENTS Title 1 Abstract 2 Contents 4 List of tables 11 List of figures 13 Acknowledgements 15 Abbreviations 16 Publications from this work 17 CHAPTER 1 - INTRODUCTION 19 1.1 General introduction 20 1.2 Aims and objectives of the thesis 22 1.3 Layout of the thesis 24 CHAPTER 2 - BACKGROUND AND LITERATURE REVIEW 26 2.1 von Willebrand’s Disease 27 2.1.1 - Historic perspective 27 2.1.2 - Biosynthesis, structure and function of von Willebrand factor 32 2.1.3 - Pathogenesis and classification of von Willebrand’s disease 35 • Type 1 35 • Type 2 36 • Type 3 38 2.1.4 - Inheritance and genetic counselling 3 9 2.1.5- Clinical manifestations 4 \ 2.1.6 - Prevalence and Diagnosis 4 4 • Clinical history 4 4 • Laboratory investigations 45 - Bleeding time 45 - Activated partial thromboplastin time 4 5 - Factor VIE assay 46 - Von Willebrand factor antigen assay 46 5 - Von Willebrand factor activity assay 46 - Ristocetin-induced platelet aggregation 47 • interpretation of laboratory results 47 • Specialised investigations for subtyping and genetic counselling 4 9 2.1.7- Treatment of von Willebrand’s disease 52 • DDAVP 53 • Other non-transfusional therapies 54 • Transfusional therapies 55 2.1.8- Treatment of specific problems in von Willebrand’s disease 58 • Bleeding from nose and mouth 5 g • Dental treatment 5 g • Menorrhagia 5 8 • Pregnancy and child birth 5 9 • Angiodysplasia and von Willebrand’s disease 60 • Surgery in patients with von Willebrand’s disease 61 2.2 Carriers of Haemophilia A and B 5 3 2.2.1 - Molecular basis of haemophilia A and B ^ 2.2.2 - Gene defects in haemophilia A and B ^ 2.2.3 - Carrier detection ^ • Family data : risk assessment ^ • Phenotypic assessment gg • Genotypic assessment gg • Timing of carrier testing 5 9 2.2.4 - Prenatal diagnosis 70 • Prenatal diagnostic techniques 70 • Laboratory techniques for genetic diagnosis 72 • Prenatal diagnosis: attitudes of carriers o f haemophilia and its psychological consequences 75 2.2.5 - Genetic counselling 77 2.2.6 - Bleeding symptoms in carriers of haemophilia 80 2.2.7 - Carriers of haemophilia and pregnancy 81 6 2.2.8 - Labour and delivery 82 2.2.9 - Obstetric haemorrhage in carriers of haemophilia 84 2.2.10 - Acquired post-partum haemophilia 85 2.3 Factor XI Deficiency 92 2.3.1 - Biochemistry and the role of factor XI in coagulation 92 2.3.2 - Molecular genetics of factor XI deficiency 95 2.3.3 - Inheritance of factor XI deficiency and preconceptional counselling 96 2.3.4 - Ethnic distribution and frequency 99 2.3.5 - Clinical manifestations 100 2.3.6- Bleeding tendency and factor XI level 101 2.3.7 - Diagnosis 103 2.3.8 - Therapeutic products available for the management of factor XI deficiency 104 • Fresh frozen plasma 104 • Factor XI concentrates 1Q5 • Fibrin glue 1 0 7 • Anti-fibrinolytic drugs 108 • DDAVP 108 2.3.9 - Factor XI inhibitors 108 2.4 Menstruation 110 2.4.1 - Definition of menorrhagia 110 2.4.2 - Assessment of menstrual blood loss 111 • Weight estimates of sanitary protections 112 • radioisotope methods 11 2 • Iron determination 112 • Haemoglobin determination ^ • Pictorial blood assessment chart ^ 2.4.3 - Menstruation and bleeding disorders 115 2.4.4 - Treatment of menorrhagia in women with inherited bleeding disorders 119 7 2.5 Desmopressin (DDAVP) 127 2.5.1-History 127 2.5.2 - Mechanism of action 128 2.5.3 - Modes of administration 130 2.5.4 - Pharmacokinetics 132 2.5.5 - DDAVP in the management of haemophilia and von Willebrand’s disease 133 2.5.6 - Other therapeutic uses of DDAVP as a haemostatic drug 135 2.5.7 - Tachyphylaxis 13 5 2.5.8 - Adverse effects and contraindications 1 3 6 2.5.9 - DDAVP in women with inherited bleeding disorders 13 g 2.5.10 - DDAVP and pregnancy 1 3 8 CHAPTER 3 - THE OBSTETRIC EXPERIENCE AND OUTCOME OF CARRIERS OF HAEMOPIHILIA 140 3.1- Introduction 141 3.2 - Patients and methods 142 3.3 - Results 143 • Prenatal diagnosis and ante-natal care 143 • Labour and mode of delivery 146 • Maternal haemorrhagic complications 149 • Neonatal complications 149 3.4 - Discussion 153 3.5- Acquired post-partum haemophilia 159 • Introduction 159 • Case report 160 • Discussion 163 CHAPTER 4 - ATTITUDES AND REPRODUCTIVE CHOICES OF WOMEN IN FAMILIES WITH HAEMOPHILIA 165 4.1- Introduction 166 4 .2 -Patients and methods 167 8 4.3- Results 169 • Prenatal diagnostic tests 170 • Termination of pregnancy 170 • Reasons for becoming pregnant 171 • Decision not to have children 173 • Information about haemophilia 174 • Identification of fetal sex 174 4.4 - Discussion 175 CHAPTER 5 - PREGNANCY IN WOMEN WITH VON WILLEBRAND’S DISEASE OR FACTOR XI DEFICIENCY 179 5.1- Introduction 180 5.2 - Patients and methods 182 5.3-Results 184 • Vaginal bleeding during pregnancy 184 • Post-abortal bleeding complications 184 • Changes in clotting factors during pregnancy 185 • Labour and mode of delivery 188 • Post-partum haemorrhage 189 • Neonatal complications 190 5.4- Discussion 193 CHAPTER 6 - VARIATIONS IN COAGULATION FACTORS IN WOMEN 200 6.1 - Introduction 2 qi 6.2 - Subjects, materials and methods 2 0 2 • Cross-sectional study 202 • Longitudinal study 202 • Statistical analysis 204 • Laboratory methods 206 6.3 - Results 210 • Cross-sectional study 210 9 • Longitudinal study 218 • Multi-level modelling results 223 6.4 - Discussion 230 CHAPTER 7 - INHERITED BLEEDING DISORDERS IN PATIENTS PRESENTING WITH MENORRHAGIA 235 7.1- Introduction 236 7.2- Patients and methods 237 7.3- Results 240 7.4- Discussion 247 CHAPTER 8 - MENSTRUATION AND INHERITED BLEEDING DISORDERS 253 8.1- Introduction 254 8.2- Patients and methods 256 8.3- Results 261 • Menstrual history 261 • Menstrual blood loss 264 • Other gynaecological problems 265 • Assessment of quality of life 267 8.4 - Discussion 273 CHAPTER 9 - DDAVP NASAL SPRAY FOR TREATMENT OF MENORRHAGIA IN WOMEN WITH INHERITED BLEEDING DISORDERS: A PROSPECTIVE RANDOMISED PLACEBO CONTROLLED CROSS-OVER STUDY 279 9.1 - Introduction 280 9.2 - Patients and methods 281 9.3 - Results 284 9.4 - Discussion 291 10 CHAPTER 10 - CONCLUSIONS AND FUTURE STUDIES 294 10.1 - Overall conclusions 295 10.2 - Suggested future research 299 LIST OF REFRENCES 304 APPENDICES 1 - Questionnaire used for assessment of attitude and reproductive choices of women in families with haemophilia 338 2 - Pictorial blood assessment chart and the scoring system used for assessment of menstrual blood loss 341 3 - Questionnaire used for assessment of quality of life in women with inherited bleeding disorders 343 11 LIST OF TABLES, (page number) Chapter 2 2.1 - Pattern of laboratory results in common types of von Willebrand’s disease. (49). 2.2 - Management of different types and subtypes of von Willebrand’s disease. (53). 2.3 - DDAVP : Routes of administration, recommended dosage and pharmacokinetics of factor VIII and von Willebrand factor response.
Load more

Recommended publications
  • Genetic and Epigenetic Determinants of Thrombin Generation Potential : an Epidemiological Approach Maria-Ares Rocanin-Arjo
    Genetic and Epigenetic Determinants of Thrombin Generation Potential : an epidemiological approach Maria-Ares Rocanin-Arjo To cite this version: Maria-Ares Rocanin-Arjo. Genetic and Epigenetic Determinants of Thrombin Generation Potential : an epidemiological approach. Génétique humaine. Université Paris Sud - Paris XI, 2014. Français. NNT : 2014PA11T067. tel-01231859 HAL Id: tel-01231859 https://tel.archives-ouvertes.fr/tel-01231859 Submitted on 21 Nov 2015 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITÉ PARIS-SUD ÉCOLE DOCTORALE 420 : SANTÉ PUBLIQUE PARIS SUD 11, PARIS DESCARTES Laboratoire : Equip 1 de Unité INSERM UMR_S1166 Genomics & Pathophysiology of Cardiovascular Diseases THÈSE DE DOCTORAT SANTÉ PUBLIQUE - GÉNÉTIQUE STATISTIQUE par Ares ROCAÑIN ARJO Genetic and Epigenetic Determinants of Thrombin Generation Potential: an epidemiological approach. Date de soutenance : 20/11/2014 Composition du jury : Directeur de thèse : David Alexandre TREGOUET DR, INSERM U1166, Université Paris 6, Jussieu Rapporteurs : Guy MEYER PU_PH, Service de pneumologie. Hôpital européen Georges Pompidou Richard REDON DR, Institut thorax, UMR 1087 / CNRS UMR 6291 , Université de Nantes Examinateurs : Laurent ABEL DR, INSERM U980, Institut Imagine Marie Aline CHARLES DR, INSERM U1018, CESP Al meu pare (to my father /à mon père) Your genetics load the gun.
    [Show full text]
  • Haemostatic Effects of Recombinant Coagulation Factor Viia
    Haemostatic effects of recombinant coagulation factor VIIa Ton Lisman Lay-out: Pre Press, Baarn Cover illustration by Janine Marie¨n Inside illustrations by Geert Donker ISBN: 90-393-3192-8 Haemostatic effects of recombinant coagulation factor VIIa Bloedstelping door recombinant stollingsfactor VIIa (Met een samenvatting in het Nederlands) PROEFSCHIFT Ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de Rector Magnificus, Prof. Dr. W.H. Gispen, in gevolge het besluit van het College voor Promoties in het openbaar te verdedigen op dinsdag 17 december 2002 des ochtends te 10.30 uur. door Johannes Antonius Lisman Geboren op 10 Maart 1976, te Arnhem Promotor: Prof. Dr. Ph.G. de Groot Faculteit geneeskunde, Universiteit Utrecht Co-Promotor: Dr. H.K. Nieuwenhuis Faculteit geneeskunde, Universiteit Utrecht The studies described in this thesis were supported in part by an unrestricted educational grant from Novo Nordisk. Financial support by Novo Nordisk for the publication of this thesis is gratefully acknowledged. I’ve got a pen in my pocket does that make me a writer Standing on the mountain doesn’t make me no higher Putting on gloves don’t make you a fighter And all the study in the world Doesn’t make it science Paul Weller Contents Chapter 1. General Introduction 9 Haemophilia Chapter 2. Inhibition of fibrinolysis by recombinant factor VIIa in plasma from patients with severe haemophilia A 41 Appendix to chapter 2. Enhanced procoagulant and antifibrinolytic potential of superactive variants of recombinant factor VIIa in plasma from patients with severe haemophilia A 55 Cirrhosis and liver transplantation Chapter 3.
    [Show full text]
  • UK National Haemophilia Database Bleeding Disorder
    UKHCDO Annual Report 2016 & Bleeding Disorder Statistics for 2015/2016 Published by United Kingdom Haemophilia Centre Doctors’ Organisation 2016 © UKHCDO 2016 Copyright of the United Kingdom Haemophilia Centre Doctors’ Organisation. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any other form by any means, electronic, mechanical, photocopying or otherwise without the prior permission in writing of the Chairman, c/o Secretariat, UKHCDO, City View House, Union Street, Ardwick, Manchester, M12 4JD. ISBN: 978-1-901787-20-7 UKHCDO Annual Report 2016 & Bleeding Disorder Statistics for 2015/2016 Contents 1. Chairman’s Report 1 2. Bleeding Disorder Statistics for 2015 / 2016 Contents 4 2.0. Comments on the Bleeding Disorder Statistics for 2015 / 2016 7 2.1 Haemophilia A 10 2.2 Haemophilia B 39 2.3 Von Willebrand Disease 56 2.4 Inhibitors Congenital and Acquired 61 2.5 Rarer Bleeding Disorders 67 2.6 Adverse Events 71 2.7 Morbidity and Mortality 74 3. Data Management Working Party 81 4. Haemtrack Group Report 84 5. Genetics Working Party 86 6. Genetic Laboratory Network 87 7. Inhibitor Working Party 89 8. Musculoskeletal Working Party 91 9. Paediatric Working Party 92 10. von Willebrand Disease Working Party 94 11. Obstetric Task Force 95 12. Therapeutic Task Force on Enhanced Half-Life Products 96 13. UK Haemophilia Data Managers’ Forum Group 97 14. Haemophilia Nurses’ Association 98 15. Haemophilia Chartered Physiotherapists’ Association 99 16. BCSH Haemostasis and Thrombosis Task Force 100 17. Haemophilia Society 102 18. The Macfarlane Trust 110 UKHCDO Annual Report 2016 & Bleeding Disorder Statistics for 2015/2016 1.
    [Show full text]
  • Acquired Bleeding Disorders Tiede, Andreas; Zieger, Barbara; Lisman, Ton
    University of Groningen Acquired bleeding disorders Tiede, Andreas; Zieger, Barbara; Lisman, Ton Published in: Haemophilia DOI: 10.1111/hae.14033 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2021 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Tiede, A., Zieger, B., & Lisman, T. (2021). Acquired bleeding disorders. Haemophilia, 27(S3), 5-13. https://doi.org/10.1111/hae.14033 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 30-09-2021 Received: 24 February 2020 | Accepted: 23 April 2020 DOI: 10.1111/hae.14033 SUPPLEMENT ARTICLE Acquired bleeding disorders Andreas Tiede1 | Barbara Zieger2 | Ton Lisman3 1Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Abstract Medical School, Hannover, Germany Acquired bleeding disorders can accompany hematological, neoplastic, autoimmune, 2 Division of Pediatric Hematology and cardiovascular or liver diseases, but can sometimes also arise spontaneously.
    [Show full text]
  • Haemostasis & Thrombosis Laboratory User Guide
    Haemostasis and Thrombosis Laboratory User Guide HAEMOSTASIS & THROMBOSIS LABORATORY USER GUIDE Document number: HPA-FO-002 WARNING: This is a controlled Page: 1 of 38 Author: Sarah Clarke document Date issued: 08/06/2020 Approved by: Head BMS Revision: 13.0 Haemostasis and Thrombosis Laboratory User Guide CONTENTS 1 INTRODUCTION ....................................................................................................... 4 2 LOCATION ................................................................................................................ 4 3 OPENING HOURS .................................................................................................... 5 3.1 Routine Coagulation Screening Service ................................................................ 5 3.2 Specialist Coagulation Service: ............................................................................. 5 4 CONTACT NUMBERS AND KEY PERSONNEL ...................................................... 6 5 CONFIDENTIALITY AND THE PROTECTION OF PERSONAL INFORMATION ..... 6 6 COMPLAINTS AND COMPLIMENTS……………………………………………………..7 7 CLINICAL INFORMATION ........................................................................................ 8 8 CLINICAL ADVICE AND INTERPRETATION ........................................................... 8 9 LABELLING OF REQUEST FORMS ........................................................................ 8 10 LABELLING OF SPECIMENS .................................................................................. 9 11 SAMPLE REQUIREMENTS
    [Show full text]
  • Hemostasis: Definition
    Bleeding disorders in children prof. Mariusz Wysocki, Katedra i Klinika Pediatrii, Hematologii i Onkologii Collegium Medicum Bydgoszcz UMK Toruń Hemostasis: definition • the sum total of those specialized functions within the circulating blood and its vessels that are intended to stop hemorrhage Hemostasis: players and phases • plasma factors • Vascular phase • inhibitors • Platelet phase • fibrinolisis • Plasma phase • platelets • vessels The coagulation system Bleeding disorders: clinical approach • history • physical examination • laboratory tests Bleeding diosrders: signs and symptoms Site Within normal May be abnormal Usually due to a limits and due to a bleeding disorder number of causes Nose Finger – induced Unilateral Recurrent, requiring medical intervention or causing anemia Oral Blood on brush Gum ooze < 30 min Gum ooze > 30 min Gut Rectal fissure, blood Haematemesis, in nappy Melaena Bleeding diorders: signs and symptoms Site Within normal May be abnormal Usually due to a limits and due to a bleeding disorder number of causes Menstrual loss 4 – 7 days „same as Mum” Loss leading to anemia or transfusion Skin Shins don’t count Bony prominences Spontaneous bruising over soft areas, laceration bleeding > 30 min Joints and muscles Trauma induced Spontaneous Intracranial Neonatal , trauma Spontaneous induced History: neonates (Sharathkumar A, 2008, Bowman M, 2009) • prolonged bleeding at the circumcision site, • cephalohematomas, • prolonged umbilical stump bleeding Warning signgs and symptoms: Epistaxis: (Sharathkumar A, 2008,
    [Show full text]
  • Spontaneous Intraocular Bleeding As an Initial Presentation of Factor XI Deficiency
    Hematocase Spontaneous intraocular bleeding as an initial presentation of Factor XI deficiency L. Duquenne, MD1, V. Schlesser, PhD2, Z. Jedidi, MD3, L. Plawny, MD4 Haemophilia C, also known as Rosenthal syndrome, is a rare disorder affecting essentially persons of Ashkenazi Jewish ascendancy. We report the case of a 79 year old patient without previous bleeding history, except for slight bruising, who presented with a severe retinal bleeding in the absence of trauma. Biology showed elevated activated partial thromboplastin time (77,7 seconds vs. normal range 30-36 seconds). Factor analysis showed isolated decreased Factor XI of 1%. No Factor XI inhibitor could be found. The patient was subsequently treated with Factor XI infusions which allowed a reduction of the bleeding and normal eyesight within four days. Spontaneous bleeding in old age is a rare inaugural sign of Factor XI deficiency, such episodes mostly occur after haemostatic challenge such as surgery or trauma leading to blood analysis and coagulation tests. Intraocular haemorrhage is an uncommon presentation of mild bleeding disorders.1-5 (Belg J Hematol 2014;5(1):22-24) Introduction most prevalent genetic defects among the Ashkenazy Haemophilia C is defined by a dysfunction of the Factor Jewish population, eight to nine percent of them presents XI activity. It can result from an impairment of secre- a heterozygous mutation while homozygosity varies tion, dimerisation or by a mechanism of heterodimer from 0.22% - 0.53%.1-3 trapping in heterozygous subjects. A bleeding score has been computed by the Interna- Factor XI (FXI) is a plasma glycoprotein that partici- tional Multicentre Study initially described for von pates in the intrinsic phase of blood coagulation.6,7 Un- Willebrand disease, defining grades of bleeding severity like other contact factors, FXI plays an important role in coagulation disorders.
    [Show full text]
  • National Bloood Authority Annual Report 2010–11
    NATIONAL BLOOD AUTHORITY BLOOD NATIONAL NATIONAL BLOOD AUTHORITY AUSTRALIA ANNUAL REPORT 2010–2011 AUSTRALIA ANNUAL REPORT ANNUAL 2010–2011 NATIONAL BLOOD AUTHORITY AUSTRALIA ANNUAL REPORT 2010–2011 Our mission is to secure a quality blood supply through world leading contractual arrangements; promote safe, high quality management and use of blood and blood products in Australia; and drive continual performance improvement across the sector. NBA 38977 Annual Report 2010-11_Text_AW4.indd i 14/10/11 5:23 PM ii 2010–11 With the exception of any logos and registered trademarks, and where otherwise noted, all material presented in this document is provided under a Creative Commons Attribution 3.0 Australia (http://creativecommons.org/licenses/by/3.0/au/) licence. ANNUAL REPORT The details of the relevant licence conditions are available on the Creative Commons NBA website (accessible using the links provided) as is the full legal code for the CC BY 3.0 AU licence (http://creativecommons.org/licenses/by/3.0/au/legalcode). The content obtained from this document or derivative of this work must be attributed as the National Blood Authority annual report 2010–11. ISSN 1832–1909 This report is available online at: www.nba.gov.au/pubs/annual-report.html Printed by: Paragon Printers Australasia Designed by: Swell Design Group Contact offi cer: Stephanie Gunn Acting CEO and General Manager Locked Bag 8430 Canberra ACT 2601 Telephone: 02 6211 8300 Facsimile: 02 6211 8330 Email: [email protected] Website: www.nba.gov.au Images of blood and blood products contained in graphics are courtesy of NBA’s suppliers.
    [Show full text]
  • Bypassing Agents Review
    National Essential Medicines List Tertiary/Quaternary Medication Review Process Bypassing Agents Date: September 2017 Medication: Haemophilia bypassing agents Recombinant Factor VIIa (rVIIa) Activated Prothrombin Complex Concentrate (aPCC) Indication: Haemophilia with inhibitors (on demand, when presenting with a significant bleed) Introduction Haemophilia refers to inherited bleeding disorders caused by deficiency of specific coagulation factors. Haemophilia A is caused by coagulation factor VIII (FVIII) deficiency, haemophilia B by deficiency of coagulation factor IX (FIX), and haemophilia C by deficiency of coagulation factor XI. These clotting factor deficiencies are caused by recessive mutations of the respective clotting factor genes. Both diseases have the same clinical presentation, so their specific diagnosis must be established by factor assay. Haemophilia A has a prevalence of about 1 in 10 000 males, while haemophilia B is less common, with a prevalence of about 1 in 35 000 males. Haemophilia A and B is treated using FVIII-replacement or Factor FIX therapy, but administration of the factor can lead to the development of anti-FVIII or FIX antibodies, commonly known as inhibitors. These inhibitors interfere with the factor function and prevent coagulation. Inhibitors are usually IgG antibodies that neutralise the procoagulant activity of FVIII or FIX. About 10 - 15% of haemophilia A patients and 1 - 3% of haemophilia B patients may develop persistent inhibitors, which make treatment with factor concentrates difficult.1 Haemophilia patients with inhibitors are at a higher risk of experiencing a bleeding episode and are more difficult to treat. Treatment of acute bleeding episodes in patients with high-responding inhibitors most often involves the use of bypassing haemostatic agents, such as plasma-derived activated prothrombin complex concentrates (aPCC) or recombinant activated Factor VII (rFVIIa).
    [Show full text]
  • Factor XI Deficiency
    Factor XI deficiency Description Factor XI deficiency is a disorder that can cause abnormal bleeding due to a shortage ( deficiency) of the factor XI protein, which is involved in blood clotting. This condition is classified as either partial or severe based on the degree of deficiency of the factor XI protein. However, regardless of the severity of the protein deficiency, most affected individuals have relatively mild bleeding problems, and some people with this disorder have few if any symptoms. The most common feature of factor XI deficiency is prolonged bleeding after trauma or surgery, especially involving the inside of the mouth and nose (oral and nasal cavities) or the urinary tract. If the bleeding is left untreated after surgery, solid swellings consisting of congealed blood (hematomas) can develop in the surgical area. Other signs and symptoms of this disorder can include frequent nosebleeds, easy bruising, bleeding under the skin, and bleeding of the gums. Women with this disorder can have heavy or prolonged menstrual bleeding (menorrhagia) or prolonged bleeding after childbirth. In contrast to some other bleeding disorders, spontaneous bleeding into the urine (hematuria), gastrointestinal tract, or skull cavity are not common in factor XI deficiency, although they can occur in severely affected individuals. Bleeding into the muscles or joints, which can cause long-term disability in other bleeding disorders, generally does not occur in this condition. Frequency Factor XI deficiency is estimated to affect approximately 1 in 1 million people worldwide. The severe deficiency disorder is much more common in people with central and eastern European (Ashkenazi) Jewish ancestry, occurring in about 1 in 450 individuals in that population.
    [Show full text]
  • Overview of the Coagulation System
    Review Article Overview of the coagulation system Address for correspondence: Sanjeev Palta, Richa Saroa, Anshu Palta1 Dr. Sanjeev Palta, Departments of Anaesthesiology and Intensive Care and 1Pathology, Government Medical College and Department of Anaesthesiology Hospital, Chandigarh, India and Intensive Care, Government Medical College and Hospital, Chandigarh, India. ABSTRACT E-mail: sanjeev_palta@yahoo. com Coagulation is a dynamic process and the understanding of the blood coagulation system has evolved over the recent years in anaesthetic practice. Although the traditional classification of the coagulation system into extrinsic and intrinsic pathway is still valid, the newer insights into coagulation provide more authentic description of the same. Normal coagulation pathway represents a balance between the pro coagulant pathway that is responsible for clot formation and the Access this article online mechanisms that inhibit the same beyond the injury site. Imbalance of the coagulation system may Website: www.ijaweb.org occur in the perioperative period or during critical illness, which may be secondary to numerous factors leading to a tendency of either thrombosis or bleeding. A systematic search of literature on DOI: 10.4103/0019-5049.144643 PubMed with MeSH terms ‘coagulation system, haemostasis and anaesthesia revealed twenty Quick response code eight related clinical trials and review articles in last 10 years. Since the balance of the coagulation system may tilt towards bleeding and thrombosis in many situations, it is mandatory
    [Show full text]
  • Open Research Online Oro.Open.Ac.Uk
    Open Research Online The Open University’s repository of research publications and other research outputs Development of a Liver Gene Therapy Strategy for Haemophilia B With Lentiviral Vectors Thesis How to cite: Cantore, Alessio (2013). Development of a Liver Gene Therapy Strategy for Haemophilia B With Lentiviral Vectors. PhD thesis The Open University. For guidance on citations see FAQs. c 2013 The Author https://creativecommons.org/licenses/by-nc-nd/4.0/ Version: Version of Record Link(s) to article on publisher’s website: http://dx.doi.org/doi:10.21954/ou.ro.0000f0bd Copyright and Moral Rights for the articles on this site are retained by the individual authors and/or other copyright owners. For more information on Open Research Online’s data policy on reuse of materials please consult the policies page. oro.open.ac.uk (v£s-nS\ creD Alessio Cantore, M.Sc. Development of a Liver Gene Therapy Strategy for Haemophilia B with Lentiviral Vectors PhD thesis in fulfilment o f the requirements o f the Open University for the degree ofDoctor o f Philosophy in Molecular and Cellular Biology 17th December 2012 Director of Studies External Supervisor Prof. Luiai Naldini Prof. Thierry VandenDriessche Additional Supervisor Prof. Maria Grazia Roncarolo Vita-Salute San Raffaele University Telethon Institute for Gene Therapy (TIGET) DIBIT, San Raffaele Scientific Institute, Milan, Italy The Open University, UK Dtfvce _s,o m\ ss vdA Z IR CL £ o 12 ProQuest Number: 13835931 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted.
    [Show full text]