Neonatal Hematology
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Neonatal
Hematology
edited by
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 , UK
Published in the United States of America by Cambridge University Press, New York
www.cambridge.org
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First published in print format 2005
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Dedication
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 pediatri-
cian, Dr Oski’s special love was neonatal hematol-
ogy. 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 pedi-
atric hematology. As Fellows, we had the privilege
and unusual experience of making neonatal hema-
tology 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 Hemato-
logic 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 under-
stand why newborns became “anemic” at birth. The
role of iron, transfusions of red cells, and vitamin E
v
vi Dedication
in the anemia of the newborn and the premature fol- was one of the most influential pediatric researchers/
lowed suit, culminating with Dr Oski’s logical next clinicians of our time. A past president of the
step, nature’s solution, breast milk, became areas to Society for Paediatric Research, she worked actively
which Dr Oski contributed throughout his career. It in research until her death, introducing the con-
is with respect and a deep felt thanks that we dedi- cept of developmental hemostasis and leading the
cate this book to our mentor Dr Oski. We also want field of thromboembolic disease in children with
to thank Dr Naiman for writing the foreword to this an evidence-based approach. As founder of the
book. He also deserves credit and gratitude for his 1-800-NO-CLOTS service, she directly helped thou-
contributions to the field of neonatal hematology sands of babies as a source of clinical expertise.
and his role in establishing this discipline. Dr Andrew trained numerous pediatricians in the
p e d r o d e a l a r c ó n a n d e r i c w e r n e r art of pediatric haematology. She will be remem-
bered by many as a brilliant scientist, a caring doc-
Dedication to Dr Maureen E. Andrew tor, a thoughtful mentor, and, for those of us lucky
enough to know her well, as a warm and wonderful
Dr Maureen Andrew (1952–2001) died suddenly friend.
during the preparation of this chapter. Dr Andrew pau l m o n a g l e
Contents
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.
vii
viii Contents
8 Neonatal screening for 13 Hemostatic abnormalities 310
hemoglobinopathies 163 Manuela Albisetti, M.D., Maureen Andrew,
Peter A. Lane, M.D. 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.
9 Polycythemia and hyperviscosity in
the newborn 171 14 Transfusion practices 349
Jayashree Ramasethu M.D. and Naomi L. C.
Ted S. Rosenkrantz, M.D. and
Luban, M.D.
William Oh, M.D.
15 Umbilical-cord stem-cell
10 Newborn platelet disorders 187 transplantation 376
Pedro A. de Alarcón, M.D. Joanne Kurtzburgh, M.D.
11 Neutrophil function and disorders of 16 Neonatal oncology 385
neutrophils in the newborn 254 Thomas D. Lamkin, M.D. and
E. Stephen Buescher, M.D. Alan S. Gamis, M.D.
17 Normal values and laboratory methods 406
12 Immunodeficiency diseases of
Pedro A. de Alarcón, M.D. and Eric J. Werner,
the neonate 280
M.D.
Matthew A. Saxonhouse, M.D. and John W.
Sleasman, M.D. Index 431
Contributors
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
Switzerland
Geoffrey A. Allen
Department of Pediatrics
University of North Carolina
418 MacNider Building, CB#7220
Chapel Hill, NC 27599-7220, USA
E. Stephen Buescher
Center for Pediatric Research
Eastern Virginia Medical School
855 W. Brambleton Ave
Norfolk, VA 23510, USA
William J. Cashore
101 Dudley Street
Providence, RI 02905, USA
ix
x List of contributors
Alan S. Gamis Department of Pediatrics
Division of Hematology / Oncology / The George Washington University
Bone Marrow Transplantation Medical Center
Children’s Mercy Hospital & Washington, DC, USA
Clinics
2401 Gillham Road Prof Paul Monagle
Kansas City, MO 64108-9898, USA Women’s & Children’s Health
Royal Children’s Hospital
Bertil Glader Flemington Road, Parkville
Stanford University Medical Center Victoria, Australia 3052
300 Pasteur Drive
Stanford, CA 94305-5208, USA William Oh
Women and Infants’ Hospital
Cris Johnson 101 Dudley St.
Children’s Hospital Central California Providence
Mailstop FC13 RI 02903
9300 Children’s Place
Madera, CA 93638, USA Howard A. Pearson
Department of Pediatrics
Pamela J. Kling Yale University School of Medicine
University of Wisconsin and
333 Cedar Street, New Haven
Meriter Hospital
CT, 06520, USA
202 S. Park St.
Madison, WI, 53715, USA
Jayashree Ramasethu
Division of Neonatology
Gary Kupfer
Georgetown University Hospital
Division of Pediatric Hematology and Oncology
3800 Reservoir Road, NW, Suite # M3400
Box 441 Jordan Hall
Washington, DC 20007, USA
University of Virginia
Charlottesville, VA 22908, USA
Ted S. Rosenkrantz
University of Connecticut Health Center
Joanne Kurtzberg
Division of Neonatal-Perinatal Medicine
Duke University Medical Center
MC 2948
Box 3350
263 Farmington Ave
Durham, NC 27710, USA
Farmington, CT 06030, USA
Thomas D. Lamkin
Doernbecher Children’s Hospital Matthew A. Saxonhouse
3181 Sam Jackson Park Road, CDRCP Division of Neonatology
Portland, OR 97239, USA Shands Children’s Hospital
University of Florida
Peter A. Lane 1600 SW Archer Road
Children’s Healthcare of Atlanta PO Box 100296
2040 Ridgewood Dr, Suite 100 Gainesville, FL 32610, USA
Atlanta, GA 30322, USA
John W. Sleasman
Naomi L. C. Luban Department of Pediatrics
Children’s National Medical Center 801 6th St. South
111 Michigan Avenue, NW All Children’s Hospital Box 9350
Washington, DC 20010, USA St Petersburg, FL 33701, USA
List of contributors xi
Eric J. Werner Peter E. Waldron
Children’s Specialty Group, Children’s Department of Pediatrics
Hospital of The King’s Daughters, University of Virginia Health System
601 Children’s Lane, Norfolk, PO Box 800386
VA 23507, USA Charlottesville VA 22908-0386, USA
Foreword
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 diagnos-
ing, treating, and preventing old diseases. These are
covered thoroughly in the chapters written by the
authors of this book, each chosen carefully by the edi-
tors 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 exam-
ple of this than in the section devoted here to
hemolytic disease of the fetus and newborn (for-
merly 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 dis-
ease of the newborn. In its place, we now see
chapters devoted to subjects hardly known then,
xiii
xiv Foreword
such as hemoglobinopathy screening, immunology, the first public cord blood bank (Placental Blood
malignancy, thromboembolic disorders, transfusion Program) at the New York Blood Center and made
practices, and umbilical-cord stem-cell harvest and these products available for hematopoietic stem-
transfusion. cell transplant programs worldwide. At this, our first
What started as a practical monograph to meeting together, he attributed his interest in the
assist clinicians dealing with hematologic problems potential of cord blood for transplantation to state-
encountered in the newborn has grown into a com- ments in our book about cord blood being a rich
prehensive reference source for everyone interested source of blood-cell precursors. At the time we wrote
in the unique aspects of blood and neoplastic dis- our book, we had no idea that statements like that
orders seen at this age – and a useful guide to those might have led to a major development such as the
directly responsible for care of these patients. use of cord blood for transplantation. But it encour-
Books such as the present one and that by Dr Oski ages me to predict that similar material in the present
and myself serve also to stimulate others to investi- book by Drs Werner and de Alarcón will provide the
gate unsolved problems and develop new therapies. seed for advances by others that were not at all con-
I was reminded of this by a chance meeting several ceived at the time this text went to press. And this is
years ago with Dr Pablo Rubinstein, who developed how the tree of knowledge grows.
J. Lawrence Naiman, M.D.
