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Neonatal Hematology
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  • 105 tables
  • Page extent: 468 pages
  • Size: 246 x 189 mm
  • Weight: 1.176 kg

Library of Congress

  • Dewey number: 618.92/01
  • Dewey version: 22
  • LC Classification: RJ269.5 .N46 2004
  • LC Subject headings:
    • Neonatal hematology

Library of Congress Record


 (ISBN-13: 9780521780704 | ISBN-10: 0521780705)

Neonatal Hematology

Written by practicing physicians specializing in pediatric hematology, neonatology, immunology, pediatric infectious disease, and transfusion medicine, this is a practical guide to the pathogenesis, recognition, and management of hematologic problems in the neonate. The focus is on clinical issues encountered by pediatric specialists. There are chapters devoted to disorders of leukocytes, platelets, procoagulant and anticoagulant proteins, and disorders of red blood cells. Neonatal transfusion, malignant disorders in the newborn, neonatal hemoglobinopathy screening, and harvesting and storage of umbilical-cord stem cells are also covered, and practical approaches to diagnosis and treatment are given.

Pedro de Alarcón is a Member of St Jude Children’s Research Hospital, Professor of Pediatrics at the University of Tennessee.

Eric Werner is Professor of Pediatrics and Director of the Division of Pediatric Hematology/Oncology at the Eastern Virginia Medical School and Co-Director of the Division of Pediatric Hematology/Oncology, Children’s Speciality Group, Children’s Hospital of the King’s Daughters.

Neonatal Hematology


Pedro A. de Alarcón
St Jude Children's Research Hospital

Eric J. Werner
Eastern Virginia Medical School and Children’s Hospital of the King’s Daughters

Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo

Cambridge University Press
The Edinburgh Building, Cambridge CB2 2RU, UK

Published in the United States of America by Cambridge University Press, New York
Information on this title:

© Cambridge University Press 2005

This publication is in copyright. Subject to statutory exception
and to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without
the written permission of Cambridge University Press.

First published 2005

Printed in the United Kingdom at the University Press, Cambridge

A catalog record for this publication is available from the British Library

Library of Congress Cataloging in Publication data
Neonatal hematology / edited by Pedro A. De Alarcón and Eric J. Werner.
 p.  cm.
Includes bibliographical references and index.
ISBN 0 521 78070 5
1. Neonatal hematology. I. De Alarcón, Pedro A., 1945– II. Werner, Eric J., 1953–
RJ269.5.N46 2004
618.92′01 – dc22 2004045496

ISBN-13 978-0-521-78070-4 hardback
ISBN-10 0-521-78070-5 hardback

Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate.

Every effort has been made in preparing this publication to provide accurate and up-to-date information that is in accord with accepted standards and practice at the time of publication. Nevertheless, the authors, editors, and publisher can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors, and publisher therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this publication. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use.


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Dedication to Dr Frank A. Oski

Our journey to the creation of this book in neonatal hematology began with a challenge from Dr Oski to update the text that he and Dr Naiman last produced in 1982. A hematologist and a consummate pediatrician, Dr Oski’s special love was neonatal hematology. We both were attracted to Syracuse, New York, not because of the wonderful weather in that sunny city of eternal snow but because of the program that Dr Oski had built both in pediatrics and in pediatric hematology. As Fellows, we had the privilege and unusual experience of making neonatal hematology rounds once a week. Dr Oski attended in the neonatal intensive care unit once a year. A MEDLINE search yields 80 publications by Dr Oski in the field of neonatal hematology. Three editions of Hematologic Problems in the Newborn, co-edited with his friend and colleague Dr Laurie Naiman, helped many of us maintain an interest in neonatal hematology. Inspired by Dr Diamond’s contributions, Drs Oski and Naiman established neonatal hematology as a field worth devoting a career to. Dr Oski contributed basic information to the field of neonatal red-cell enzymes, the neonatal red cell as it differed from the characteristic red cell in children and adults. Oxygen delivery and the hemoglobin dissociation curve were a natural sequence of study in an attempt to understand why newborns became “anemic” at birth. The role of iron, transfusions of red cells, and vitamin E in the anemia of the newborn and the premature followed suit, culminating with Dr Oski’s logical next step, nature’s solution, breast milk, became areas to which Dr Oski contributed throughout his career. It is with respect and a deep felt thanks that we dedicate this book to our mentor Dr Oski. We also want to thank Dr Naiman for writing the foreword to this book. He also deserves credit and gratitude for his contributions to the field of neonatal hematology and his role in establishing this discipline.


Dedication to Dr Maureen E. Andrew

Dr Maureen Andrew (1952–2001) died suddenly during the preparation of this chapter. Dr Andrew was one of the most influential pediatric researchers/ clinicians of our time. A past president of the Society for Paediatric Research, she worked actively in research until her death, introducing the concept of developmental hemostasis and leading the field of thromboembolic disease in children with an evidence-based approach. As founder of the 1-800-NO-CLOTS service, she directly helped thousands of babies as a source of clinical expertise. Dr Andrew trained numerous pediatricians in the art of pediatric haematology. She will be remembered by many as a brilliant scientist, a caring doctor, a thoughtful mentor, and, for those of us lucky enough to know her well, as a warm and wonderful friend.



List of contributors page ix
Foreword xiii
Preface xv
1   Neonatal hematology: a historical overview 1
  Howard A. Pearson, M.D.
2   Disorders of the fetomaternal unit 10
  Eric J. Werner, M.D.
3   Erythropoiesis, red cells, and the approach to anemia 40
  Pedro A. de Alarcón, M.D., M. Cris Johnson, M.D. and Eric J. Werner, M.D.
4   Anemia of prematurity and indications for erythropoietin therapy 58
  Pamela J. Kling, M.D.
5   Hypoplastic anemia 68
  Gary Kupfer, M.D.
6   Hemolytic disease of the fetus and newborn 91
  Peter E. Waldron, M.D. and William J. Cashore, M.D.
7   Neonatal hemolysis 132
  Bertil Glader, M.D., Ph.D. and Geoffrey Allen, M.D.
8   Neonatal screening for hemoglobinopathies 163
  Peter A. Lane, M.D.
9   Polycythemia and hyperviscosity in the newborn 171
  Ted S. Rosenkrantz, M.D. and William Oh, M.D.
10   Newborn platelet disorders 187
  Pedro A. de Alarcón, M.D.
11   Neutrophil function and disorders of neutrophils in the newborn 254
  E. Stephen Buescher, M.D.
12   Immunodeficiency diseases of the neonate 280
  Matthew A. Saxonhouse, M.D. and John W. Sleasman, M.D.
13   Hemostatic abnormalities 310
  Manuela Albisetti, M.D., Maureen Andrew, M.D., F.R.C.P.C. and Paul Monagle, M.B.B.S., M.Sc., F.R.A.C.P., F.R.C.P.A.
14   Transfusion practices 349
  Jayashree Ramasethu M.D. and Naomi L. C. Luban, M.D.
15   Umbilical-cord stem-cell transplantation 376
  Joanne Kurtzburgh, M.D.
16   Neonatal oncology 385
  Thomas D. Lamkin, M.D. and Alan S. Gamis, M.D.
17   Normal values and laboratory methods 406
  Pedro A. de Alarcón, M.D. and Eric J. Werner, M.D.
  Index 431


Pedro A. de Alarcón
St. Jude Children’s Research Center
Danny Thomas, Founder
Mail stop #103
332 N. Lauderdale St.
Memphis, TN 38105–3991, USA

Manuela Albisetti
University Children’s Hospital
Steinwiesstrasse 75
8032 Zurich

Geoffrey A. Allen
Department of Pediatrics
University of North Carolina
418MacNider Building, CB#7220
Chapel Hill, NC 27599–7220, USA

E. Stephen Buescher
Center for Pediatric Research
Eastern VirginiaMedical School
855W. Brambleton Ave
Norfolk, VA 23510, USA

William J. Cashore
101 Dudley Street
Providence, RI 02905, USA

Alan S. Gamis
Division of Hematology / Oncology /
BoneMarrow Transplantation
Children’sMercy Hospital &
2401 Gillham Road
Kansas City,MO 64108–9898, USA

Bertil Glader
Stanford UniversityMedical Center
300 Pasteur Drive
Stanford, CA 94305–5208, USA

Cris Johnson
Children’s Hospital Central California
Mailstop FC13
9300 Children’s Place
Madera, CA 93638, USA

Pamela J. Kling
University ofWisconsin and
Meriter Hospital
202 S. Park St.
Madison, WI, 53715, USA

Gary Kupfer
Division of Pediatric Hematology and Oncology
Box 441 Jordan Hall
University of Virginia
Charlottesville, VA 22908, USA

Joanne Kurtzberg
Duke UniversityMedical Center
Box 3350
Durham, NC 27710, USA

Thomas D. Lamkin
Doernbecher Children’s Hospital
3181 SamJackson Park Road, CDRCP
Portland, OR 97239, USA

Peter A. Lane
Children’s Healthcare of Atlanta
2040 Ridgewood Dr, Suite 100
Atlanta, GA 30322, USA

Naomi L. C. Luban
Children’s NationalMedical Center
111Michigan Avenue, NW
Washington, DC 20010, USA
Department of Pediatrics
The GeorgeWashington University
Medical Center
Washington, DC, USA

Prof Paul Monagle
Women’s & Children’s Health
Royal Children’s Hospital
Flemington Road, Parkville
Victoria, Australia 3052

William Oh
Women and Infants’ Hospital
101 Dudley St.
RI 02903

Howard A. Pearson
Department of Pediatrics
Yale University School ofMedicine
333 Cedar Street, New Haven
CT, 06520, USA

Jayashree Ramasethu
Division of Neonatology
Georgetown University Hospital
3800 Reservoir Road, NW, Suite # M3400
Washington, DC 20007, USA

Ted S. Rosenkrantz
University of Connecticut Health Center
Division of Neonatal–PerinatalMedicine
MC 2948
263 Farmington Ave
Farmington, CT 06030, USA

Matthew A. Saxonhouse
Division of Neonatology
Shands Children’s Hospital
University of Florida
1600 SW Archer Road
PO Box 100296
Gainesville, FL 32610, USA

John W. Sleasman
Department of Pediatrics
801 6th St. South
All Children’s Hospital Box 9350
St Petersburg, FL 33701, USA

Eric J. Werner
Children’s Specialty Group, Children’s
Hospital of The King’s Daughters,
601 Children’s Lane, Norfolk,
VA 23507, USA

Peter E. Waldron
Department of Pediatrics
University of Virginia Health System
PO Box 800386
Charlottesville VA 22908–0386, USA


It is an honor to be invited to write a foreword to this book. I know my friend and late colleague Dr Frank A. Oski, with whom I coauthored three editions of the monograph Hematology of the Newborn from 1966 to 1982, would echo this sentiment. And he would be delighted that his former fellows Drs Werner and de Alarcón shared our interest in the importance of this subject sufficiently to bring it up to date in an expanded textbook rich with information of great scientific and practical value.

 As expected, there have been many important advances in the field of neonatal hematology in the past 20 years – new diseases, new ways of diagnosing, treating, and preventing old diseases. These are covered thoroughly in the chapters written by the authors of this book, each chosen carefully by the editors for his or her expert knowledge and experience.

 With progress, diseases that virtually established neonatal hematology as a distinct discipline have largely come under control, reducing the space needs for describing them. There is no greater example of this than in the section devoted here to hemolytic disease of the fetus and newborn (formerly referred to as erythroblastosis fetalis), one that represented the largest chapter in our earlier monograph. All this resulted from the successful implementation in 1968 of Rh immunoglobulin to prevent Rh alloimmunization and hemolytic disease of the newborn. In its place, we now see chapters devoted to subjects hardly known then, such as hemoglobinopathy screening, immunology, malignancy, thromboembolic disorders, transfusion practices, and umbilical-cord stem-cell harvest and transfusion.

 What started as a practical monograph to assist clinicians dealing with hematologic problems encountered in the newborn has grown into a comprehensive reference source for everyone interested in the unique aspects of blood and neoplastic disorders seen at this age – and a useful guide to those directly responsible for care of these patients.

 Books such as the present one and that by Dr Oski and myself serve also to stimulate others to investigate unsolved problems and develop new therapies. I was reminded of this by a chance meeting several years ago with Dr Pablo Rubinstein, who developed the first public cord blood bank (Placental Blood Program) at the New York Blood Center and made these products available for hematopoietic stem-cell transplant programs worldwide. At this, our first meeting together, he attributed his interest in the potential of cord blood for transplantation to statements in our book about cord blood being a rich source of blood-cell precursors. At the time we wrote our book, we had no idea that statements like that might have led to a major development such as the use of cord blood for transplantation. But it encourages me to predict that similar material in the present book by Drs Werner and de Alarcón will provide the seed for advances by others that were not at all conceived at the time this text went to press. And this is how the tree of knowledge grows.

J. Lawrence Naiman, M.D.


There is no time in life when human physiology changes more rapidly than in the neonatal period. The blood is very much affected by the transition from the intrauterine to the extrauterine environment. During this time, the normal range becomes a moving target, making it difficult to distinguish many abnormalities from physiologic variations. Furthermore, remarkable advances in perinatal/neonatal medicine have led to dramatic improvements in infant survival – now extending to the extremely low-birthweight infant. Many previously fatal congenital disorders are no longer universally so, due both to advances in basic and clinical research and to the hard work of perinatologists, neonatologists, pediatricians, pediatric subspecialists, and surgeons.

 Melissa Warfield, M.D., a pediatric hematologist of great experience, would refer to textbooks as either “How come?” books or “How to” books. It is the goal of this textbook to be a “How to” book, with some discussion of the pathophysiology of the hematologic problems while focussing on practical aspects for the clinician. While there is some overlap between each of the areas covered in this book, as there is with most of the hematologic disorders of the newborn, we have chosen to be inclusive of the discussions prepared by each of the contributors.

 The contributors to this text bring a wealth of knowledge and expertise to each of the chapters. We are so fortunate to have readily acknowledged experts with a wide range of backgrounds, including neonatologists, pediatric hematologists, pediatric immunologists, pediatric transfusion medicine specialists, and pediatric infectious diseases physicians. These authors took time from their very busy activities to review the state of the art in their fields, often dealing with repeated questions and requests from the editors. In particular, we, and the entire medical world, will greatly miss Dr Maureen Andrew. In addition to her extensive research into hematologic problems of the newborn, especially in the area of thromboembolic disease, she could always be called upon for her wisdom and experience in the management of difficult clinical problems.

 We thank Dr J. Lawrence Naiman for his continuous support through the production of this text and Drs James A. Stockman Ⅲ and Jack Widness for their insightful comments and criticisms. Lastly, but certainly not the least, we wish to thank our wives (Jill and Alice), our children (Alessandro, Tessa, Jacob, Abby, and Andrew), and the patient spouses and children of all of our contributors whose family activities were limited by their dedication to completing this text.

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