The Oxford Handbook of Clinical Haematology provides core and concise information on the entire spectrum of blood disorders affecting both adults and children. Updated for its fourth edition, it includes all major advances in the specialty, including malignant haematology, haematooncology, coagulation, transfusion medicine, and red cell disorders, with a brand new chapter on rare diseases. Practically focused, and specifically designed for easeofuse, and rapid access to the information you need, this handbook is an indispensable resource on all aspects of haematology for all trainee doctors, nurses, technicians, and research professionals. The handbook is divided into clinical approach and diseasespecific areas. The clinical approach section outlines various symptoms and signs in patients with blood disease to enable the reader to formulate a sensible differential diagnosis beofre embarking on investigation and treatment. The diseasespecific section is written by four authors whose expertise covers the whole breadth of diseases included in the book. All authors have contributed to national guidelines (e.g. British Committee for Standards in Haematology, BCSH) and are experts in the evidence base that exists for each topic. The Oxford Handbook of Clinical Haematology offers a concise and logical approach to caring for patients with diseases of the blood.
Haematological emergencies Septic shock/neutropenic fever E p636 Acute transfusion reactions E p638 Delayed transfusion reaction E p642 Post-transfusion purpura E p643 Hypercalcaemia E p644 Hyperviscosity E p646 Disseminated intravascular coagulation E p648 Overdosage of thrombolytic therapy E p651 Heparin overdosage E p652 Heparin-induced thrombocytopenia (HIT) E p654 Warfarin overdosage E p656 Massive blood transfusion E p658 Paraparesis/spinal collapse E p662 Leucostasis E p663 Thrombotic thrombocytopenic purpura E p664 Sickle crisis E p666 Tumour lysis syndrome (TLS) E p690 oxford medical publications Oxford Handbook of Clinical Haematology Published and forthcoming Oxford Handbooks Oxford Handbook for the Foundation Programme 4/e Oxford Handbook of Acute Medicine 3/e Oxford Handbook of Anaesthesia 2/e Oxford Handbook of Applied Dental Sciences Oxford Handbook of Cardiology 2/e Oxford Handbook of Clinical and Laboratory Investigation 2/e Oxford Handbook of Clinical Dentistry 6/e Oxford Handbook of Clinical Diagnosis 3/e Oxford Handbook of Clinical Examination and Practical Skills 2/e Oxford Handbook of Clinical Haematology 4/e Oxford Handbook of Clinical Immunology and Allergy 3/e Oxford Handbook of Clinical Medicine—Mini Edition 9/e Oxford Handbook of Clinical Medicine 9/e Oxford Handbook of Clinical Pharmacy Oxford Handbook of Clinical Rehabilitation 2/e Oxford Handbook of Clinical Specialties 9/e Oxford Handbook of Clinical Surgery 4/e Oxford Handbook of Complementary Medicine Oxford Handbook of Critical Care 3/e Oxford Handbook of Dental Patient Care 2/e Oxford Handbook of Dialysis 3/e Oxford Handbook of Emergency Medicine 4/e Oxford Handbook of Endocrinology and Diabetes 3/e Oxford Handbook of ENT and Head and Neck Surgery Oxford Handbook of Epidemiology for Clinicians Oxford Handbook of Expedition and Wilderness Medicine Oxford Handbook of Gastroenterology and Hepatology Oxford Handbook of General Practice 4/e Oxford Handbook of Genitourinary Medicine, HIV and AIDS Oxford Handbook of Geriatric Medicine 2/e Oxford Handbook of Infectious Diseases and Microbiology Oxford Handbook of Key Clinical Evidence Oxford Handbook of Medical Sciences 2/e Oxford Handbook of Nephrology and Hypertension 2/e Oxford Handbook of Neurology 2/e Oxford Handbook of Nutrition and Dietetics Oxford Handbook of Obstetrics and Gynaecology 3/e Oxford Handbook of Occupational Health 2/e Oxford Handbook of Oncology 3/e Oxford Handbook of Ophthalmology 3/e Oxford Handbook of Paediatrics 2/e Oxford Handbook of Palliative Care 2/e Oxford Handbook of Practical Drug Therapy Oxford Handbook of Pre-Hospital Care Oxford Handbook of Psychiatry 2/e Oxford Handbook of Public Health Practice 3/e Oxford Handbook of Reproductive Medicine and Family Planning 2/e Oxford Handbook of Respiratory Medicine 3/e Oxford Handbook of Rheumatology 3/e Oxford Handbook of Sport and Exercise Medicine Oxford Handbook of Tropical Medicine 4/e Oxford Handbook of Urology 3/e Oxford Handbook of Clinical Haematology FOURTH EDITION Drew Provan Reader in Haematology Barts & The London School of Medicine and Dentistry Queen Mary University of London, UK Trevor Baglin Consultant Haematologist Addenbrooke’s NHS Trust Cambridge, UK Inderjeet Dokal Chair of Child Health and Centre Lead Barts & The London School of Medicine and Dentistry Queen Mary University of London Honorary Consultant Barts Health NHS Trust London, UK Johannes de Vos Consultant Haematologist Royal Surrey County Hospital NHS Foundation Trust Guildford, UK 1 Great Clarendon Street, Oxford, OX2 6DP, United Kingdom Oxford University Press is a department of the University of Oxford It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries © Oxford University Press 2015 The moral rights of the authors have been asserted First Edition published in 1998 Second Edition published in 2004 Third Edition published in 2009 Fourth Edition published in 2015 Impression: All rights reserved No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without the prior permission in writing of Oxford University Press, or as expressly permitted by law, by licence or under terms agreed with the appropriate reprographics rights organization Enquiries concerning reproduction outside the scope of the above should be sent to the Rights Department, Oxford University Press, at the address above You must not circulate this work in any other form and you must impose this same condition on any acquirer Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America British Library Cataloguing in Publication Data Data available Library of Congress Control Number: 2014943849 Typeset by Greengate Publishing Services, Tonbridge, UK ISBN 978-0-19-968330-7 Printed in China by C&C Offset Printing Co Ltd Oxford University Press makes no representation, express or implied, that the drug dosages in this book are correct Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulations The authors and the publishers not accept responsibility or legal liability for any errors in the text or for the misuse or misapplication of material in this work Except where otherwise stated, drug dosages and recommendations are for the non-pregnant adult who is not breast-feeding Links to third party websites are provided by Oxford in good faith and for information only Oxford disclaims any responsibility for the materials contained in any third party website referenced in this work v Preface to the fourth edition The world of haematology has been exciting over the past few years, and we have seen major advances since the third edition of the Oxford Handbook of Clinical Haematology was published These are most obvious in haemato-oncology, with the development of new agents and regimens for treating malignant haematology disorders But there have also been advances in haemostasis and red cell haematology with the arrival of the novel oral anticoagulation drugs and new oral chelators for the treatment of iron overload, in addition to a number of other advances This edition sees a change of editorial team and we are very happy to have John de Vos, haemato-oncologist, on board He has overhauled the haemato-oncology sections bringing them thoroughly up to date We have also sought the advice of Shubha Allard, consultant in transfusion medicine, to make sure the blood transfusion section is accurate, in addition to Banu Kaya, a red cell haematologist who has brought the red cell material up to date For the first time, we have incorporated a new chapter on rare disorders which we hope readers will find useful We are very grateful to the editorial team at Oxford University Press for their patience and hard work, especially Liz Reeve and Michael Hawkes There may be errors or omissions from the book and we would welcome any comments or feedback (email drewprovan@mac.com) We will try to incorporate these in future editions DP TB ID JdV January 2014 vi Preface to the third edition It is hard to believe that at least three years have passed since the second edition of the handbook As with all medical specialties, Haematology has seen major inroads with new diagnostic tests, treatments and a plethora of guidelines In fact, Haematology has the largest collection of guidelines covering all aspects of haematology care (M http://www bcshguidelines com) and was the first specialty to design guidelines in the 1980s The book underwent a major revision with the second edition, most notably the sections dealing with malignant disease For the new edition these have been brought right up to date by Charles Singer Coagulation has been entirely rewritten by Trevor Baglin and now truly reflects the current investigation and management of coagulation disorders Following the retirement of Professor Sir John Lilleyman we needed to find a new author for the Paediatric Haematology component of the book Thankfully, we were able to persuade Professor Inderjeet Dokal to take on this mantle and he has revised this section thoroughly In addition to these significant changes, we have gone through the entire book and attempted to ensure that obsolete tests have been removed and that the Handbook, in its entirety, reflects contemporary haematology practice As ever, we are very keen to hear about errors or omissions, for which we are entirely responsible! We would also very much like readers to contact us if there are topics or subject areas which they would like to see included in the fourth edition We also need more trainee input so if there are any volunteer proof-readers or accuracy checkers among the haematology trainee community we would very much like to hear from you DP CRJS TB ISD 2008 vii Foreword to the fourth edition The Concise Oxford English Dictionary defines a handbook as ‘a short manual or guide’ Modern haematology is a vast field which involves almost every other medical speciality and which, more than most, straddles the worlds of the basic biomedical sciences and clinical practice Since the rapidly proliferating numbers of textbooks on this topic are becoming denser and heavier with each new edition, the medical student and young doctor in training are presented with a daunting problem, particularly as they try to put these fields into perspective And those who try to teach them are not much better placed; on the one hand they are being told to decongest the curriculum, while on the other they are expected to introduce large slices of molecular biology, social science, ethics, and communication skills, not to mention a liberal sprinkling of poetry, music, and art In this over-heated educational scene the much maligned ‘handbook’ could well stage a comeback and gain new respectability, particularly in the role of a friendly guide In the past this genre has often been viewed as having little intellectual standing, of no use to anybody except the panic-stricken student who wishes to try to make up for months of misspent time in a vain, one-night sitting before their final examination But given the plethora of rapidly changing information that has to be assimilated, the carefully prepared précis is likely to play an increasingly important role in medical education Perhaps even that ruination of the decent paragraph and linchpin of the pronouncements of medical bureaucrats, the ‘bullet point’, may become acceptable, albeit in small doses, as attempts are made to highlight what is really important in a scientific or clinical field of enormous complexity and not a little uncertainty In the fourth edition of this short account of blood diseases the editors have continued to provide an excellent service to medical students, as well as doctors who are not specialists in blood diseases, by summarizing in simple terms the major features and approaches to diagnosis and management of most of the blood diseases that they will encounter in routine clinical practice or in the tedious examinations that face them And, of equal importance, they have been able to update and summarize some of the major advances that have been made in this rapidly moving field since the appearance of the early editions of this handbook As in previous editions they have managed to avoid one of the major pitfalls of this type of teaching: in trying to reduce complex issues down to their bare bones it is all too easy to introduce inaccuracies One word of warning from a battle-scarred clinician however A précis of this type suffers from the same problem as a set of multiple-choice questions Human beings are enormously complex organisms, and sick ones are even more complicated; during a clinical lifetime the self-critical doctor will probably never encounter a ‘typical case’ of anything Thus the viii FOREWORD TO THE FOURTH EDITION outlines of the diseases that are presented in this book must be used as approximate guides, and no more But provided they bear this in mind, students will find that it is a very valuable summary of modern haematology; the addition of the Internet sources is a genuine and timely bonus D J Weatherall Oxford, June 2014 Fig 2.4 Hypersegmented neutrophils with 7–8 lobes: found in B12 or folate deficiency Note: blood films and marrow appearances are identical in B12 and folate deficiencies (E see Fig. 2.4 p.49) Fig 2.11 Blood film in hereditary spherocytosis Note: large numbers of dark spherical red cells (E see Fig. 2.11 p.86) Fig 4.1 Bone marrow showing myeloblasts in AML (E see Fig. 4.1 p.125) Fig 4.2 Bone marrow showing myeloblasts in AML (E see Fig. 4.2 p 125) Fig 4.3 AML: myeloblast with large Auer rod (left) (E see Fig. 4.3 p.125) Fig 4.4 AML: myeloblast with large Auer rod (top of cell) (E see Fig. 4.4 p.126) Fig 4.5 AML: Sudan Black stain (dark granules clearly seen in myeloblasts) (E see Fig. 4.5 p.126) Fig 4.6 Gum hypertrophy in patient with AML (E see Fig. 4.6 p.131) Fig 4.8 Bone marrow: lymphoblasts in ALL L1 (E see Fig. 4.8 p.141) Fig 4.9 Bone marrow: T-cell ALL showing numerous lymphoblasts (E see Fig. 4.9 p.142) Fig 4.10 Peripheral blood film in CML: note large numbers of granulocytic cells at all stages of differentiation (low power) (E see Fig. 4.10 p.149) Fig 4.11 Peripheral blood film in CML: high power (E see Fig. 4.11 p.150) Fig 4.12 Blood film in CLL showing smear cells (bottom of field) (E see Fig. 4.12 p.159) Fig 4.15 Blood film in PLL: cells are larger than those seen in CLL have large prominent nucleoli and moderate chromatin condensation (E see Fig. 4.15 p.169) Fig 4.16 Blood film in HCL showing typical ‘hairy’ lymphocytes (medium power) (E see Fig. 4.16 p.171) Fig 4.17 Blood film in HCL showing typical ‘hairy’ lymphocytes (high power) (E see Fig. 4.17 p.171) Fig 4.19(a) Blood films showing typical ATL cell with lobulated ‘clover leaf ’ nucleus’ (E see Fig. 4.19(a) p.179) Fig 4.19(b) Blood films showing typical ATL cell with lobulated ‘clover leaf ’ nucleus’ (E see Fig. 4.19(b) p.179) Fig 5.1 Blood film in Sézary syndrome showing typical cerebriform nuclei (E see Fig. 5.1 (a) p.200) Fig 5.2 PET and CT scans in patient with nodular sclerosing Hodgkin lymphoma demonstrating active disease (moderate FDG uptake on PET) in residual anterior mediastinal mass on CT after ABVD chemotherapy (E see Fig. 5.2 p.218) Fig 6.1 Blood film in MDS showing bilobed pseudo-Pelger neutrophil (E see Fig. 6.1 p.236) Fig 6.2 Bone marrow in RARS stained for iron: note iron granules round the nucleus of the erythroblast (E see Fig. 6.2 p.243) Fig 7.1 Bone marrow trephine in myelofibrosis: note streaming effect caused by intense fibrosis (E see Fig. 7.1 p.294) Fig 8.1 Electrophoresis: from L l R: urine with BJP and generalized proteinuria (albumin band at top of strip, BJP near foot); serum M band in myeloma; polyclonal gammopathy; normal sample, showing albumin, α, E, and γ globulins (E see Fig. 8.1 p.338) Fig 8.2 Bone marrow aspirate in myeloma showing numerous plasma cells (E see Fig. 8.2 p.341) Plate Radiograph of pelvis in a patient with multiple myeloma showing abnormal low density bone texture in the left superior pubic ramus and ischium (E see p.338) Plate MRI of cervical and thoracic spine in a patient with multiple myeloma: substantial extra-osseous mass at T1 displacing the spinal cord anteriorly and causing some cord compression (E see Investigations and diagnosis p.338) Plate MRI of pelvis in a patient with multiple myeloma (same as Plate 29 ) showing corresponding soft tissue mass replacing bone & numerous widespread foci of signal change throughout the bony pelvis representing myeloma deposits (E see p.338) Plate T1 sagittal sequence MRI of thoraco-lumbar spine in a patient with multiple myeloma showing multiple myeloma deposits and partial collapse of one vertebral body (E see p.338) ... Clinical Dentistry 6/e Oxford Handbook of Clinical Diagnosis 3/e Oxford Handbook of Clinical Examination and Practical Skills 2/e Oxford Handbook of Clinical Haematology 4/e Oxford Handbook of. .. of Clinical Immunology and Allergy 3/e Oxford Handbook of Clinical Medicine—Mini Edition 9/e Oxford Handbook of Clinical Medicine 9/e Oxford Handbook of Clinical Pharmacy Oxford Handbook of Clinical. .. Rehabilitation 2/e Oxford Handbook of Clinical Specialties 9/e Oxford Handbook of Clinical Surgery 4/e Oxford Handbook of Complementary Medicine Oxford Handbook of Critical Care 3/e Oxford Handbook of Dental