Postgraduate Haematology, Sixth edition - Hörbücher · • Interactive multiple-choice questions prepared by the authors. EDITED BY A Victor Hoffbrand MA, DM, FRCP, FRCPath, FRCP

EDITED BY

A Victor Hoffbrand MA, DM, FRCP, FRCPath, FRCP (Edin), DSc, FMedSciEmeritus Professor of Haematology at University College London and Honorary Consultant Haematologist at the Royal Free Hospital, London, UK

Daniel Catovsky MD, DSc (Med), FRCPath, FRCP, FMedSciEmeritus Professor of Haematology, Institute of Cancer Research, Sutton, Surrey, UK

Edward GD Tuddenham MD, FRCP, FRCPath, FMedSciProfessor of Haemophilia at University College London and Director of the Haemophilia Centre at Royal Free Hospital, London, UK

Anthony R Green PhD, FRCP, FRCPath, FMedSciProfessor of Haemato-oncology, Department of Haematology and Cambridge Institute for Medical Research, University of Cambridge; Honorary Consultant at Addenbrookes Hospital, Cambridge, UK

Sixth edition

Postgraduate Haematology

A John Wiley & Sons, Ltd., Publication

Companion website

This book has a companion website:

www.wiley.com/go/hoffbrand/postgraduate

with:

Figures and tables from the book for downloading Interactive multiple-choice questions prepared by the authors

EDITED BY

A Victor Hoffbrand MA, DM, FRCP, FRCPath, FRCP (Edin), DSc, FMedSciEmeritus Professor of Haematology at University College London and Honorary Consultant Haematologist at the Royal Free Hospital, London, UK

Daniel Catovsky MD, DSc (Med), FRCPath, FRCP, FMedSciEmeritus Professor of Haematology, Institute of Cancer Research, Sutton, Surrey, UK

Edward GD Tuddenham MD, FRCP, FRCPath, FMedSciProfessor of Haemophilia at University College London and Director of the Haemophilia Centre at Royal Free Hospital, London, UK

Anthony R Green PhD, FRCP, FRCPath, FMedSciProfessor of Haemato-oncology, Department of Haematology and Cambridge Institute for Medical Research, University of Cambridge; Honorary Consultant at Addenbrookes Hospital, Cambridge, UK

Sixth edition


A John Wiley & Sons, Ltd., Publication

This edition fi rst published 2011 2005 by Blackwell Publishing Ltd

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First published as Tutorials in Postgraduate Haematology William Heinemann Ltd 1972Reprinted 1975Second edition 1981 published Butterworth LtdReprinted 1983, 1986Third edition 1989 published Butterworth LtdReprinted 1992Fourth edition 1999 published Butterworth-Heinmann LtdRevised and reprinted 2001 by ArnoldFifth edition 2005Reprinted 2005

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Library of Congress Cataloging-in-Publication Data

Postgraduate haematology / edited by A. Victor Hoffbrand ... [et al.]. 6th ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4051-9180-7 1. BloodDiseases. 2. Hematology. I. Hoffbrand, A. V. [DNLM: 1. Blood. 2. Hematologic Diseases. WH 100 P857 2011] RC633.P67 2011 616.15dc22

2009046376

A catalogue record for this book is available from the British Library.

This book is published in the following electronic formats: ePDF 9781444323177; Wiley Online Library 9781444323160

Set in 9.5/12pt Minion by Toppan Best-set Premedia Limited

1 2011

www.wiley.com/wiley-blackwell

v

Contents

Contributors, vii

Preface to the sixth edition, xi

Preface to the fi rst edition, xii

1 Stem cells and haemopoiesis, 1 Elaine Dzierzak

2 Erythropoiesis, 12 Douglas R Higgs and William G Wood

3 Iron metabolism, iron defi ciency and disorders of haem synthesis, 26

A Victor Hoffbrand, Chaim Hershko and Clara Camaschella

4 Iron overload, 47 Clara Camaschella and A Victor Hoffbrand

5 Megaloblastic anaemia, 61 A Victor Hoffbrand

6 Haemoglobin and the inherited disorders of globin synthesis, 83

Swee Lay Thein and David Rees

7 Sickle cell disease, 109 Ashutosh Lal and Elliott P Vichinsky

8 Hereditary disorders of the red cell membrane, 126

Edward C Gordon-Smith and Narla Mohandas

9 Disorders of red cell metabolism, 140 Alberto Zanella and Edward C Gordon-Smith

10 Acquired haemolytic anaemias, 158 Edward C Gordon-Smith and Modupe O Elebute

11 Paroxysmal nocturnal haemoglobinuria, 176 Peter Hillmen

12 Inherited aplastic anaemia/bone marrow failure syndromes, 186

Inderjeet S Dokal

13 Acquired aplastic anaemia, 206 Judith CW Marsh and Neal S Young

14 Red cell immunohaemotology: introduction, 226 Marcela Contreras and Geoff Daniels

15 Antigens in human blood, 244 Marcela Contreras and Geoff Daniels

16 Clinical blood transfusion, 268 Marcela Contreras, Clare PF Taylor and

John A Barbara

17 Phagocytes, 300 John Mascarenhas, Farhad Ravandi and

Ronald Hoffman

18 Lysosomal storage disorders, 330 Atul B Mehta and Derralynn A Hughes

19 Normal lymphocytes and non-neoplastic lymphocyte disorders, 343

Paul AH Moss and Mark T Drayson

20 The spleen, 368 Paul AH Moss

21 The molecular basis of leukaemia and lymphoma, 380 George S Vassiliou and Anthony R Green

22 Laboratory diagnosis of haematological neoplasms, 395

Barbara J Bain and Torsten Haferlach

23 Acute myeloid leukaemia, 415 Alan K Burnett and Adriano Venditti

24 Adult acute lymphoblastic leukaemia, 433 Nicola Gkbuget and Dieter Hoelzer

25 Childhood acute lymphoblastic leukaemia, 448 Dario Campana and Ching-Hon Pui

26 Supportive care in the management of leukaemia, 463

Archibald G Prentice and J Peter Donnelly

27 Chronic myeloid leukaemia, 483 John M Goldman and Tariq I Mughal

28 The myelodysplastic syndromes, 503 Timothy JT Chevassut and Ghulam J Mufti

Contents

vi

29 Chronic lymphocytic leukaemia and other B-cell disorders, 530

Daniel Catovsky and Emili Montserrat

30 T-cell lymphoproliferative disorders, 558 Estella Matutes

31 Multiple myeloma, 577 Jess San-Miguel and Joan Blad

32 Amyloidosis, 599 Simon DJ Gibbs and Philip N Hawkins

33 The classifi cation of lymphoma: updating the WHO classifi cation, 614

Elias Campo and Stefano A Pileri

34 Hodgkin lymphoma, 639 Jonathan Sive and David Linch

35 Non-Hodgkin lymphoma, 655 Kate Cywnarski and Anthony H Goldstone

36 Myeloproliferative neoplasms, 686 Peter J Campbell and Anthony R Green

37 Histocompatibility, 710 Ann-Margaret Little, Steven GE Marsh and

J Alejandro Madrigal

38 Stem cell transplantation, 722 Charles Craddock and Ronjon Chakraverty

39 Normal haemostasis, 746 Keith Gomez, Edward GD Tuddenham and

John H McVey

40 The vascular function of platelets, 772 Stephen P Watson and Paul Harrison

41 Inherited bleeding disorders, 793 Michael A Laffan and K John Pasi

42 Rare bleeding disorders, 813 Flora Peyvandi and Marzia Menegatti

43 Acquired coagulation disorders, 839 Peter W Collins, Jecko Thachil and Cheng-Hock Toh

44 Thrombotic thrombocytopenic purpura and haemolyticuraemic syndrome (congenital and acquired), 860

Pier M Mannucci, Flora Peyvandi and Roberta Palla

45 Heritable thrombophilia, 872 Trevor Baglin

46 Acquired venous thrombosis, 888 Beverley J Hunt and Michael Greaves

47 Management of venous thromboembolism, 900 Beverly J Hunt

48 Congenital platelet disorders, 915 Maurizio Margaglione and Paul RJ Ames

49 Primary immune thrombocytopenia, 928 Drew Provan and Adrian C Newland

50 Haematological aspects of systemic disease, 940 Atul B Mehta and A Victor Hoffbrand

51 Haematological aspects of tropical diseases, 956 Imelda Bates and Ivy Ekem

52 Neonatal haematology, 971 Irene AG Roberts

Appendix I Normal values, 985

Appendix II World Health Organization classifi cation of tumours of the haematopoietic and lymphoid tissues, 986

Index, 989


Companion website

This book has a companion website:


with:

Figures and tables from the book for downloading Interactive multiple-choice questions prepared by the authors

vii

Contributors

Paul RJ Ames Consultant Haematologist Department of Haematology Airedale General Hospital Steeton UK

Trevor Baglin Consultant Haematologist Department of Haematology Cambridge University Hospitals NHS Trust Addenbrookes Hospital Cambridge UK

Barbara J Bain Department of Haematology St Mary s Hospital London UK

John A Barbara Emeritus Microbiology Consultant NHS Blood and Transplant Colindale London UK

Imelda Bates Reader in Tropical Haematology Liverpool School of Tropical Medicine Liverpool UK

Joan Blad Senior Consultant Haematologist Servicio de Hematolog a Hospital Clinic de Barcelona Barcelona Spain

Alan K Burnett Department of Haematology School of Medicine Cardiff University Cardiff UK

Clara Camaschella Professor of Medicine Vita - Salut University; Division of Genetics and Cell Biology San Raffaele Scientifi c Institute Milan Italy

Dario Campana Vice Chair for Laboratory Research Departments of Oncology and Pathology St Jude Children s Research Hospital Memphis, TN USA

Peter J Campbell Cancer Genome Project Wellcome Trust Sanger Institute Cambridge UK

Elias Campo Clinical Director and Professor of Pathology Center for Biomedical Diagnosis and Chief of

Hematopathology Unit Hospital Clinic University of Barcelona Barcelona Spain

Daniel Catovsky Emeritus Professor of Haematology Institute of Cancer Research Sutton Surrey UK

Ronjon Chakraverty Royal Free and University College Medical School London UK

Timothy JT Chevassut Senior Lecturer and Honorary Consultant in

Haematology Brighton and Sussex Medical School Royal Sussex County Hospital Brighton UK

Peter W Collins Senior Lecturer in Haematology Department of Haematology School of Medicine Cardiff University University Hospital of Wales Cardiff UK

Marcela Contreras University College London and Blood Transfusion

International London UK

Charles Craddock Centre for Clinical Haematology Leukaemia Unit Queen Elizabeth Hospital Birmingham UK

Kate Cwynarski Consultant Haematologist and Honorary Senior

Lecturer Department of Haematology Royal Free Hospital London UK

Geoff Daniels Consultant Clinical Scientist Bristol Institute for Transfusion Sciences NHS Blood and Transplant Bristol UK

Contributors

viii

Inderjeet S Dokal Chair of Paediatrics and Child Health Centre Lead Barts and The London School of Medicine and

Dentistry Queen Mary University of London Barts and The London Children s Hospital London UK

J Peter Donnelly Department of Haematology University Hospital Nijmegen Nijmegen The Netherlands

Mark T Drayson Department of Immunology University of Birmingham Medical School Birmingham UK

Elaine Dzierzak Department of Cell Biology Erasmus Stem Cell Institute Erasmus Medical Centre Rotterdam The Netherlands

Ivy Ekem Senior Lecturer and Head Department of Haematology University of Ghana Medical School Accra Ghana

Modupe O Elebute Consultant Haematologist King s College Hospital London UK

Simon DJ Gibbs Clinical Academic Research Fellow (Haematology) National Amyloidosis Centre University College London Medical School; Royal Free Hospital London UK

Nicola G kbuget Head of Study Center Goethe University Hospital Department of Medicine II Hematology/Oncology Frankfurt Germany

John M Goldman Department of Haematology Imperial College School of Medicine Hammersmith Hospital London UK

Anthony H Goldstone Department of Haematology University College London London UK

Keith Gomez Senior Lecturer in Haematology Haemophilia Centre and Thrombosis Unit Royal Free and University College London

Medical School London UK

Edward C Gordon - Smith Department of Haematology St George s Hospital Medical School London UK

Michael Greaves Professor of Haematology Head of School of Medicine and Dentistry University of Aberdeen Aberdeen UK

Anthony R Green Department of Haematology University of Cambridge Cambridge Institute for Medical Research Cambridge UK

Torsten Haferlach MLL Munich Leukemia Laboratory GmbH Munich Germany

Paul Harrison Clinical Scientist Oxford Haemophilia and Thrombosis Centre The Churchill Hospital Headington Oxford UK

Philip N Hawkins Clinical Director National Amyloidosis Centre University College London Medical School Royal Free Hospital London UK

Chaim Hershko Department of Medicine Shaare Zedek Medical Centre; Professor Emeritus Hebrew U Hadassah Medical School Jerusalem Israel

Douglas R Higgs Professor of Molecular Haematology MRC Molecular Haematology Unit Weatherall Institute of Molecular Medicine John Radcliffe Hospital Oxford UK

Peter Hillmen Department of Haematology St James s University Hospital Leeds UK

Dieter Hoelzer Professor of Internal Medicine Onkologikum Frankfurt Museum Embankment Frankfurt Germany

A Victor Hoffbrand Emeritus Professor of Haematology University College Medical School; Honorary Consultant Haematologist Royal Free Hospital London UK

Ronald Hoffman Albert A and Vera List Professor of Medicine Tisch Cancer Institute Mount Sinai School of Medicine New York, NY USA

Derralynn A Hughes Senior Lecturer in Haematology Department of Academic Haematology Royal Free and University College Medical School London UK

Contributors

ix

Beverley J Hunt Thrombosis and Haemostasis King s College; Guy s and St Thomas NHS Foundation Trust London UK

Michael A Laffan Department of Haematology, Faculty of Medicine Imperial College School of Medicine Hammersmith Hospital London UK

Ashutosh Lal Hematology/Oncology Children s Hospital and Research Center at

Oakland Oakland, CA USA

David Linch Department of Haematology UCL Medical School London UK

Ann - Margaret Little Histocompatibility and Immunogenetics Service Gartnavel General Hospital Glasgow UK

John H McVey Weston Professor of Molecular Medicine Molecular Medicine Thrombosis Research Institute London UK

J Alejandro Madrigal The Anthony Nolan Research Institute Royal Free Hospital London UK

Pier M Mannucci Professor and Chairman of Internal Medicine A. Bianchi Bonomi Hemophilia and Thrombosis

Center IRCCS C Granada Maggiore Hospital Foundation; Department of Internal Medicine University of Milan and Luigi Villa Foundation Milan Italy

Maurizio Margaglione Associate Professor Medical Genetics Department of Biomedical Sciences University of Foggia Foggia Italy

Judith CW Marsh Department of Haematological Medicine King s College Hospital London UK

Steven GE Marsh The Anthony Nolan Research Institute Royal Free Hospital London UK

John Mascarenhas Assistant Professor of Medicine Division of Hematology/Oncology Tisch Cancer Institute Mount Sinai School of Medicine New York, NY USA

Estella Matutes Reader and Consultant Haematologist Royal Marsden Hospital and Institute of Cancer

Research London UK

Atul B Mehta Consultant Haematologist Department of Haematology University College London School of Medicine Royal Free Hospital London UK

Marzia Menegatti A. Bianchi Bonomi Hemophilia and Thrombosis


Narla Mohandas Vice President of Research New York Blood Center New York, NY USA

Emili Montserrat Director, Institute of Hematology and Oncology Hospital Clinic University of Barcelona Barcelona Spain

Paul AH Moss Professor of Haematology and Head of School of

Cancer Sciences University of Birmingham Birmingham UK

Ghulam J Mufti Head, Department of Haematological Medicine King s College Hospital and Kings College London London UK

Tariq I Mughal Guy s Hospital London UK

Adrian C Newland Professor of Haematology Department of Haematology Queen Mary University of London London UK

Roberta Palla A. Bianchi Bonomi Hemophilia and Thrombosis


K John Pasi Centre for Haematology Institute of Cell and Molecular Science Barts and The London School of Medicine and

Dentistry London UK

Flora Peyvandi Associate Professor of Internal Medicine A. Bianchi Bonomi Hemophilia and Thrombosis


Contributors

x

Stefano A Pileri Professor of Pathology Department of Haematology and Oncological

Sciences; Director of the Haematopathology Unit Bologna University School of Medicine St Orsola Hospital Bologna Italy

Archibald G Prentice Department of Haematology Royal Free Hospital London UK

Drew Provan Senior Lecturer in Haematology Department of Haematology Queen Mary University of London London UK

Ching - Hon Pui Departments of Oncology and Pathology St Jude Children s Research Hospital Memphis, TN USA

Farhad Ravandi Department of Leukaemia University of Texas MD Anderson Cancer Center Houston, TX USA

David Rees Senior Lecturer King s College Hospital; Consultant Paediatric Haematologist Department of Haematological Medicine King s College London School of Medicine London UK

Irene AG Roberts Professor of Paediatric Haematology Centre for Haematology Hammersmith Campus Imperial College London London UK

Jes s San - Miguel Professor and Chairman of Haematology Department of Haematology Hospital Universitario de Salamanca Salamanca Spain

Jonathan Sive Department of Haematology UCM Medical School London UK

Clare PF Taylor Medical Director of SHOT Medical Directorate North London Blood Centre London UK

Jecko Thachil Clinical Research Fellow in Haematology School of Clinical Sciences University of Liverpool Liverpool UK

Swee Lay Thein Professor of Molecular Haematology Department of Haematological Medicine King s College Hospital; Consultant Haematologist Division of Gene and Cell Based Therapy King s College London School of Medicine London UK

Cheng - Hock Toh Professor of Haematology School of Clinical Sciences University of Liverpool Liverpool UK

Edward GD Tuddenham Katharine Dormandy Chair of Haemophilia Haemophilia Centre and Thrombosis Unit Royal Free and University College London

Medical School London UK

George Vassiliou Wellcome Trust Sanger Institute Wellcome Trust Genome Campus Cambridge UK

Adriano Venditti Associate Professor Department of Haematology Policlinico Tor Vergata Rome Italy

Elliott P Vichinsky Hematology/Oncology Children s Hospital and Research Center at

Oakland Oakland, CA USA

Stephen P Watson BHF Chair in Cardiovascular Sceinces and

Cellular Pharmacology Division of Medical Sciences Institute of Biomedical Research Centre for Cardiovascular Sciences University of Birmingham Birmingham UK

William G Wood Professor in Haematology Weatherall Institute of Molecular Medicine John Radcliffe Hospital Oxford UK

Neal S Young National Heart, Lung, and Blood Institute National Institutes of Health Bethesda, MD USA

Alberto Zanella Hematology 2 Unit IRCCS C Granada Maggiore Hospital Foundation Milan Italy

xi

Preface to the s ixth e dition

Haematology continues to advance and change more rapidly than most areas of medicine. This sixth edition of Postgraduate Haematology includes much knowledge that has been gained in the fi ve years since the previous edition. Professor Tony Green of the Department of Haematology, University of Cambridge has joined the editors of the last edition to help cover malignant diseases, where major changes have occurred in their classifi ca-tion (WHO, 2008) and in diagnostic procedures and treatment protocols. Haematological oncology now forms the major workload for many consultant haematologists. Nevertheless, benign conditions are a major source of work for the general haematologist and chapters concerning all these conditions have been extensively updated, often by new authors.

Despite increased understanding of the molecular basis of haematological diseases and advances in their investigation and management, we have kept the size of the book unchanged by omitting ten chapters from the fi fth edition and incorporating their essential information into the remaining chapters.

As for previous editions, this book is aimed at providing haematologists in training and consultants with up - to - date knowledge of the aetiology of blood diseases combined with a practical guide to their investigation and treatment. The views expressed are those of the individual authors but relevant litera-ture is listed at the end of each chapter to provide additional reference material.

Many of our authors are based outside the UK, particularly in Europe and the USA, and we hope this book will be used by haematologists practising in the UK, Europe and internation-ally. We are grateful to our publishers Wiley - Blackwell for their unstinting help during the publishing process and particularly to Rebecca Huxley and Jennifer Seward. We also thank Jane Fallows who, as previously, has with great expertise drawn all the scientifi c diagrams.

London and Cambridge, 2011 AVH, DC, EGDT, ARG

xii

Preface to the fi rst e dition

In this book the authors combine an account of the physiologi-cal and biochemical basis of haematological processes with descriptions of the clinical and laboratory features and manage-ment of blood disorders. Within this framework, each author has dealt with the individual subjects as he or she thought appropriate. Because this book is intended to provide a founda-tion for the study of haematology and is not intended to be a reference book, it refl ects, to some extent, the views of the individual authors rather than providing comprehensive detail and a full bibliography. For these the reader is referred to the selected reading given at the end of each chapter. It is hoped that the book will prove of particular value to students taking either the Primary or the Final Part of the examination for Membership of the Royal College of Pathologists and the Diplomas of Clinical Pathology. It should also prove useful to physicians wishing to gain special knowledge of haematology and to technicians taking the Advanced Diploma in Haematology of the Institute of Medical Laboratory Technology, or the Higher National Certifi cate in Medical Laboratory subjects.

We wish to acknowledge kind permission from the editors and publishers of the British Journal of Haematology , the Journal

of the Royal College of Physicians of London and the Quarterly Journal of Medicine for permission to reproduce fi gures 4.1, 4.5, 4.10, 4.11, 4.12, 9.4 and 9.10, also the publishers of Progress in Haematology for fi gure 7.2, and many other publishers who, together with the authors, have been acknowledged in the text. We are particularly grateful to Professor J.V. Dacie for provid-ing material which formed the basis of many of the original illustrations in Chapters 4 8 . We are greatly indebted to Mrs T. Charalambos, Mrs J. Cope and Mrs D. Haysome for secretarial assistance and to Mrs P. Schilling and the Department of Medical Illustration for photomicrography, art work and general photography.

Finally, we are grateful for the invaluable help and forbear-ance we have received from Mr R. Emery and William Heinemann Medical Books.

London, 1972 AVH SML

1

Postgraduate Haematology : 6th edition. Edited by A. Victor Hoffbrand, Daniel Catovsky, Edward G.D. Tuddenham, Anthony R. Green 2011 Blackwell Publishing Ltd.

CHAPTER 1

Stem c ells and h aemopoiesis Elaine Dzierzak Erasmus Stem Cell Institute, Erasmus Medical Centre, Rotterdam, The Netherlands

1

Introduction , 1 Hierarchical organization and lineage

relationships in the adult haemopoietic system , 1

Sites of adult haemopoiesis , 3 Development of HSCs , 3 Waves of haemopoietic generation in embryonic

development, 3

Embryonic haemopoietic sites and haemopoietic migration, 5

HSC quiescence, proliferation and ageing, 6 Haemopoietic supportive

microenvironments , 6 Adult bone marrow microenvironment, 6 Microenvironments important for haemopoietic

development in the conceptus, 7

Haemopoietic regenerative and replacement therapies , 8

Stem cell transplantation, 8 New sources of HSCs for transplantation, 8 Selected bibliography , 10

Introduction

Haemopoietic stem cells (HSCs) are the foundation of the adult blood system and sustain the lifelong production of all blood lineages. These rare cells are generally defi ned by their ability to self - renew through a process of asymmetric cell division, the outcome of which is an identical HSC and a differentiating cell. Through a series of proliferation and differentiation events, mature blood cells are produced. In health, HSCs provide homeostatic maintenance of the system through their ability to generate the hundreds of millions of erythrocytes and leuco-cytes needed each day. In trauma and physiological stress, HSCs are triggered to replace the lost or damaged blood cells. The tight regulation of HSC self - renewal ensures the appropriate balance of blood cell production. Perturbation of this regula-tion and unchecked growth of HSCs and/or immature blood cells results in leukaemia. Over the last 50 years, bone marrow transplantation, and more recently cord blood transplantation, have underscored the medical value of stem cell regenerative therapy. However, insuffi cient numbers of HSCs are still a major constraint in clinical applications. As the pivotal cells in this essential tissue, HSCs are the focus of intense research to further our understanding of their normal behaviour and the basis of their dysfunction in haemopoietic disease and leukae-mia, and to provide insights and new strategies into improved clinical transplantation therapies. This chapter provides current and historical information on the organization of the adult haemopoietic cell differentiation hierarchy, the ontogeny of HSCs, the stromal microenvironment supporting these cells,

and the molecular mechanisms involved in the regulation of HSCs.

Hierarchical o rganization and l ineage r elationships in the a dult h aemopoietic s ystem

The haemopoietic system is the best - characterized cell lineage differentiation hierarchy and, as such, has set the paradigm for the growth and differentiation of tissue - specifi c stem cells (Table 1.1 ). HSCs are defi ned by their high proliferative poten-tial, ability to self - renew and potential to give rise to all haemo-poietic lineages. HSCs produce immature progenitors that gradually and progressively, through a series of proliferation and differentiation events, become restricted in lineage differ-entiation potential. Such restricted progenitors produce the terminally differentiated functional blood cells.

The lineage relationships of the variety of cells within the adult haemopoietic hierarchy (Figure 1.1 ) are based on results of in vivo transplantation assays in radiation chimeric mice and many in vitro differentiation assays that became available following the identifi cation of haemopoietic growth factors. These assays facilitated measurement of the maturational pro-gression of stem cells and progenitors, at or near the branch points of lineage commitment. Clonal analyses, in the form of colony - forming unit (CFU) assays, were developed to defi ne the lineage differentiation potential of the stem cell or progenitor, and to quantitate the number/frequency of such cells in the population as a whole. In general, the rarer a progenitor is and the greater its lineage differentiation potential, the closer it is in the hierarchy to the HSC. In vitro clonogenic assays measure the most immature progenitor CFU - GEMM/Mix (granulocyte, erythroid, macrophage, megakaryocyte), bipotent progenitors

Postgraduate Haematology, Sixth editionContentsContributorsPreface to the sixth editionPreface to the first editionCHAPTER 1: Stem cells and haemopoiesisCHAPTER 2: ErythropoiesisCHAPTER 3: Iron metabolism, iron deficiency and disorders of haem synthesisCHAPTER 4: Iron overloadCHAPTER 5: Megaloblastic anaemiaCHAPTER 6: Haemoglobin and the inherited disorders of globin synthesisCHAPTER 7: Sickle cell diseaseCHAPTER 8: Hereditary disorders of the red cell membraneCHAPTER 9: Disorders of red cell metabolismCHAPTER 10: Acquired haemolytic anaemiasCHAPTER 11: Paroxysmal nocturnal haemoglobinuriaCHAPTER 12: Inherited aplastic anaemia/bone marrow failure syndromesCHAPTER 13: Acquired aplastic anaemiaCHAPTER 14: Red cell immunohaematology: introductionCHAPTER 15: Antigens in human bloodCHAPTER 16: Clinical blood transfusionCHAPTER 17: PhagocytesCHAPTER 18: Lysosomal storage disordersCHAPTER 19: Normal lymphocytes and non-neoplastic lymphocyte disordersCHAPTER 20: The spleenCHAPTER 21: The molecular basis of leukaemia and lymphomaCHAPTER 22: Laboratory diagnosis of haematological neoplasmsCHAPTER 23: Acute myeloid leukaemiaCHAPTER 24: Adult acute lymphoblastic leukaemiaCHAPTER 25: Childhood acute lymphoblastic leukaemiaCHAPTER 26: Supportive care in the management of leukaemiaCHAPTER 27: Chronic myeloid leukaemiaCHAPTER 28: The myelodysplastic syndromesCHAPTER 29: Chronic lymphocytic leukaemia and other B-cell disordersCHAPTER 30: T-cell lymphoproliferative disordersCHAPTER 31: Multiple myelomaCHAPTER 32: AmyloidosisCHAPTER 33: The classification of lymphomas: updating the WHO classificationCHAPTER 34: Hodgkin lymphomaCHAPTER 35: Non-Hodgkin lymphomaCHAPTER 36: Myeloproliferative neoplasmsCHAPTER 37: HistocompatibilityCHAPTER 38: Stem cell transplantationCHAPTER 39: Normal haemostasisCHAPTER 40: The vascular function of plateletsCHAPTER 41: Inherited bleeding disordersCHAPTER 42: Rare bleeding disordersCHAPTER 43: Acquired coagulation disordersCHAPTER 44: Thrombotic thrombocytopenic purpura and haemolyticuraemic syndrome (congenital and acquired)CHAPTER 45: Heritable thrombophiliaCHAPTER 46: Acquired venous thrombosisCHAPTER 47: Management of venous thromboembolismCHAPTER 48: Congenital platelet disordersCHAPTER 49: Primary immune thrombocytopeniaCHAPTER 50: Haematological aspects of systemic diseaseCHAPTER 51: Haematological aspects of tropical diseasesCHAPTER 52: Neonatal haematologyAPPENDIX 1: Normal valuesAPPENDIX 2: World Health Organization classification of tumours of the haematopoietic and lymphoid tissuesIndex

Documents

Postgraduate Haematology, Sixth edition - Hörbücher · • Interactive multiple-choice questions prepared by the authors. EDITED BY A Victor Hoffbrand MA, DM, FRCP, FRCPath, FRCP