Transfusion Medicine and Hemostasis: Clinical and Laboratory Aspects

706 Pages·2009·7.34 MB·English

by  Christopher D. Hillyer MD

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First edition 2009
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About the Editors
Christopher D. Hillyer, MD, is the Emory Distinguished Service Professor of
Pathology, and atenured professor in the Department of Pathology and Laboratory
Medicine, Emory University School of Medicine. In these capacities, he serves as direc-
tor of the Emory Center for Transfusion and Cellular Therapies with responsibility for
all aspects of clinical and academic transfusion medicine at Emory’s seven principle
hospitals. Dr. Hillyer is chief editor of three textbooks in transfusion medicine, author
of over 120 articles pertaining to transfusion, human immunodeficiency virus (HIV),
cytokines, and herpes viruses, most notably Cytomegalovirus (CMV), as well as more
than 25 book chapters. Nationally recognized as an expert in hematology blood bank-
ing, and transfusion medicine, Dr. Hillyer also is a past-president, board of directors
of AABB (formerly known as the American Association of Blood Banks) and a former
trustee of the National Blood Foundation (NBF). Dr. Hillyer has been awarded many
million dollars in research funding from the National Institutes of Health (NIH), the
Centers for Disease Control and Prevention (CDC), NBF and other agencies. He is an
associate editor of the journal Transfusion and serves on several other editorial boards
including the journal Blood. Dr. Hillyer was recently recognized as a Healthcare Hero
for his work in Africa and is a recipient of the Tiffany Award from the American Red
Cross where he also serves as a medical director. Dr. Hillyer is board certified in four
specialty areas including transfusion medicine, hematology, medical oncology and
internal medicine. He received his BS from Trinity College (1980), and his MD from
the University of Rochester School of Medicine (1984), with postgraduate training
and fellowships in hematology-oncology, transfusion medicine and bone marrow
transplantation at Tufts-New England Medical Center in Boston.
Beth H. Shaz, MD, is an associate professor in the Department of Pathology and
Laboratory Medicine, Emory University School of Medicine, and serves as director
of the blood bank at Grady Memorial Hospital and co-director of clinical research at
the Center for Transfusion and Cellular Therapy. Prior to moving to Emory she was
the assistant medical director of the Transfusion Services and medical director of the
Transfusion and Apheresis Unit at Beth Israel Deaconess Medical Center. She has writ-
ten many articles and book chapters pertaining to transfusion, cellular therapy, and
therapeutic apheresis. Nationally, she is chair of the Clinical Applications Committee
of the American Society for Apheresis, which has recently published new and evi-
dence-based guidelines for the use of therapeutic apheresis. In addition, she is the
chair of the Transfusion Services Accreditation Program Unit and the Blood Banking/
Transfusion Medicine Fellowship Program Directors Subsection of the AABB.
Dr. Shaz is board certified in transfusion medicine, clinical and anatomic pathol-
ogy. She received her BS from Cornell University and her MD from the University of
Michigan School of Medicine. Her postgraduate training includes a general surgery
internship at Georgetown University, and residency in clinical and anatomic pathology
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 AbouttheEditors
and fellowship in transfusion medicine at Beth Israel Deaconess Medical Center, a
major teaching hospital of Harvard Medical School in Boston.
James C. Zimring, MD, PhD, is an tenured associate professor in the Department
of Pathology and Laboratory Medicine, Emory University School of Medicine,
and serves as the assistant director of the special hemostasis laboratory at Emory
University Hospital. Dr. Zimring oversees the laboratory diagnosis of patients with
disorders in thrombosis and hemostasis. In addition, Dr. Zimring has an active NIH
funded research program studying the immunology of transfusion and bone mar-
row transplantation. Dr. Zimring is a recent recipient of the David B. Pall award for
advances in transfusion medicine, and frequently presents original research in the field
of transfusion at national and international meetings. He is on the editorial board of
the journal Transfusion and serves as a reviewer for additional journals in the fields of
transfusion and coagulation. Dr. Zimring has authored several book chapters in the
fields of transfusion, coagulation and molecular pathology. He is board certified in
Clinical Pathology and received a BS in Chemistry, PhD in Immunology, and an MD
all from Emory University.
Thomas C. Abshire, MD, is a professor in the Department of Pediatrics Emory
University School of Medicine, and the director of the Comprehensive Hemostasis
Program, Emory University and Children’s Healthcare of Atlanta. He also serves as
the Pediatric Hematology/Oncology Fellowship Program Director at Emory and
Children’s. Prior to joining the faculty at Emory University, Dr. Abshire completed a
career in the United States Air Force with an emphasis as a clinician-educator, where
he was the recipient of several medical student and housestaff teaching awards. Dr.
Abshire’s research interest is in evaluation of mild bleeding disorders and therapeutic
intervention in hemophilia, von Willebrand disease and thrombosis. He has published
over 60 peer-reviewed manuscripts, review articles or editorials and is a frequent
invited speaker at national and international meetings. He also serves on the Steering
Committee of the International Immune Tolerance Study and recently was a member
on the CDC Uniform Data Collection Committee. He has received research funding
from the NIH, CDC, and several non profit organizations and pharmaceutical com-
panies. Dr. Abshire is a past-president of the Hemophilia and Thrombosis Research
Society. Dr. Abshire is a distinguished graduate of the US Air Force Academy. He
attended medical school at Tulane University, fulfilled his pediatric residency training
at David Grant USAF Medical Center and completed pediatric hematology/oncology
fellowship training at the University of Colorado Health Science Center.
Contributors
THOMAS C. ABSHIRE, MD
Professor, Department of Pediatrics, Emory University School of Medicine
Director’s Chair in Hemostasis, Hemophilia of Georgia, Inc.
Director, Comprehensive Hemostasis Program, Emory University and Children’s
Healthcare of Atlanta, Atlanta, Georgia, USA
CAROLYN M. BENNETT, MD
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s
Healthcare of Atlanta, Atlanta, Georgia, USA
MICHAEL A. BRIONES, DO
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s
Healthcare of Atlanta, Atlanta, Georgia, USA
MARY D. DARROW, MD
Resident Physician, Department of Pathology and Laboratory Medicine, Emory
University School of Medicine, Atlanta, Georgia, USA
AMY L. DUNN, MD
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s
Healthcare of Atlanta, Atlanta, Georgia, USA
JIMMIE L. EVANS, MT (ASCP)
Manager, Transfusion Medicine Laboratory Services, Emory University Hospital,
Atlanta, Georgia, USA
LAWRENCE B. FIALKOW, DO
Fellow, Center for Transfusion Medicine and Cellular Therapies, Department of
Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta,
Georgia, USA
COURTNEY E. GREENE, MD
Resident Physician, Department of Pathology and Laboratory Medicine, Emory
University School of Medicine, Atlanta, Georgia, USA
ALFRED J. GRINDON, MD
Professor Emeritus, Department of Pathology and Laboratory Medicine, Emory
University School of Medicine, Atlanta, Georgia, USA
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 Contributors
ELEANOR S. HAMILTON, MT (ASCP)
Medical Technologist, Cellular Therapies Laboratory, Emory University Hospital,
Atlanta, Georgia, USA
JEANNE E. HENDRICKSON, MD
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Assistant Director, Blood Banks and Transfusion Services, Children’s Healthcare of
Atlanta, Atlanta, Georgia, USA
CHRISTOPHER D. HILLYER, MD
Distinguished Service Professor of Pathology
Professor, Department of Pathology and Laboratory Medicine, Emory University
School of Medicine
Professor, Department of Hematology and Medical Oncology, Emory University
School of Medicine
Director, Center for Transfusion and Cellular Therapies, Atlanta, Georgia, USA
KRISTA L. HILLYER, MD
Assistant Professor, Department of Pathology and Laboratory Medicine, Emory
University School of Medicine
Chief Medical Officer, Southest Division, American Red Cross Blood Services,
Douglasville, Georgia, USA
SHAWN M. JOBE, MD, PhD
Assistant Professor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s
Healthcare of Atlanta, Atlanta, Georgia, USA
CASSSANDRA D. JOSEPHSON, MD
Associate Professor, Department of Pathology and Laboratory Medicine, Emory
University School of Medicine
Associate Director, Blood Banks and Transfusion Services, Children’s Healthcare of
Atlanta, Atlanta, Georgia, USA
CHRISTINE L. KEMPTON, MD
Assistant Professor, Department of Pediatrics and Department of Hematology and
Medical Oncology, Emory University School of Medicine
Assistant Professor,
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s
Healthcare of Atlanta, Atlanta, Georgia, USA
SHANNON L. MEEKS, MD
Instructor, Department of Pediatrics, Emory University School of Medicine
Attending Physician, Aflac Cancer Center and Blood Disoders Service, Children’s
Healthcare of Atlanta, Atlanta, Georgia, USA
CONNIE H. MILLER, PhD
Director, Clinical Hemostasis Laboratory,
Division of Blood Disorders, National Center on Birth Defects and Developmental
Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Preface
The editors present this inaugural edition of Transfusion Medicine and Hemostasis –
Clinical and Laboratory Aspects with great excitement and anticipation.
As the title indicates, we view, and have done so for some time, that both transfusion
medicine and hemostasis, particularly laboratory methods and diagnostic tests employed
in routine and specialized coagulation laboratories, are linked. More specifically, coagu-
lation tests, and indeed other laboratory tests and results, are often used to guide and
monitor transfusion, blood component and coagulation factor therapy. Also, transfu-
sion strategies are used to treat patients with disorders of hemostasis which have been
previously diagnosed using specialized and vital hemostasis and coagulation laboratory
tests and methods. In addition, pathology, pediatric and internal medicine residents, and
transfusion medicine and hematology fellows, often receive training (to varying extents)
in blood banking and transfusion medicine, and in disorders and diseases of congenital
and acquired coagulation defects, though a combined and appropriately focused book
does not appear to exist. Moreover, books that focus on critical and technical elements
of laboratory testing methodologies, in the context of transfusion and hemostasis, are
few – if any. Indeed, in our institution both transfusion medicine and the coagulation/
hemostasis laboratories are housed in the same clinical and administrative place – the
Emory Center for Transfusion and Cellular Therapies – and joint consultation services
exist. It is thus that we envisioned a manual-style book combining transfusion medicine
and hemostasis/coagulation medicine. Indeed, the book before you is divided into these
two main parts, as the title obviously suggests.
Not surprisingly, others have noted the interdigitation of these two fields – such as
those who conceived the Transfusion Medicine/Hemostasis Clinical Trials Network, now
funded by the National Institutes of Health. Also, board certification in blood banking and
transfusion medicine is currently accomplished via the American Board of Pathology, and
the examination has a significant emphasis on clinical hemostasis and laboratory aspects
of coagulation as well as blood banking and transfusion medicine. Interestingly, board
eligibility in transfusion medicine, following an accredited transfusion medicine fellow-
ship, can be achieved directly via internal medicine, pediatrics and anesthesia residencies,
in addition to pathology and adult and pediatric hematology. Thus, it is our intention that
this offering be of value to trainees in many specialties, as well as fellows in transfusion
medicine and hematology. Moreover, as transfusion is the most common therapeutic
modality in use in the US, it is anticipated that this book will provide valuable information
for practitioners in a variety of fields, including anesthesiology, surgery and obstetrics.
The format of this book is intentional, with shorter, concise chapters being the
norm. In each chapter, the intent is to have clear paragraphs, bullet points, and tables
and figures, with a hierarchy of headings so that presentation of key points will be
most efficient. Where possible and appropriate, a common hierarchical format has
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 Preface
been employed. Instead of an exhaustive list of references, the editors have chosen
to offer a small number of key articles from which the reader may gain additional
information. Even without the usual citation-based technical writing style typically
employed in books, we have tried to incorporate evidence-based and data-driven
prose, and have referred to specific authors, studies, and publications in a way that
will allow the reader to find a specific reference even when it is not cited at the end of a
chapter. We fervently hope this style will be efficient, informative and enjoyable.
As stated above, the book is divided into two main parts – transfusion medicine and
hemostasis. That on transfusion medicine is further subdivided into blood banking (that
is, blood collection, processing, testing and storage) and transfusion medicine (that is,
components for transfusion, pretransfusion immunohematology testing, product modi-
fications, approaches to transfusion therapy in specific clinical settings, and transfusion
reactions and complications). Also included are apheresis, cellular therapy, and an intro-
duction to tissue banking in the hospital setting. These chapters and sub-parts follow
introductory chapters with common elements defining the field of blood banking and
transfusion medicine, a brief history, and quality and regulatory principles. We have also
included chapters focused on the role of the physician in both the blood collection facil-
ity and the transfusion service, as well as descriptions of careers in the field.
In the second main part of the book, dedicated to hemostasis, the chapters are further
divided into sub-parts – clinical coagulation, laboratory-based coagulation testing, and
coagulation factor products. While these three sub-parts could have been compressed
into a disease-based chapter system, we felt that focus on the clinical issues, the labora-
tory and testing methods and details to diagnose and guide and monitor therapy, and
finally the products available to treat the conditions, would be helpful and ease assimila-
tion of the material. We hope you will agree.
Finally, in many places throughout the book, we have sections or paragraphs dedi-
cated to international considerations. These are not exhaustive and were not meant to
be, especially as regulatory requirements and practice variations vary widely through-
out the developed and the developing, world. Nonetheless, the editors felt it was
important to broaden the horizon of this book to have somewhat of a “world view.”
Again, we hope you will agree.
In closing, we are deeply dedicated to the fields of transfusion medicine and hemosta-
sis, the ambition of striving towards optimal diagnosis, laboratory testing and therapies
for patients worldwide, and the education of trainees, practitioners and future leaders
in these inter-related disciplines. We hope this book will fill a void, achieve a new vision,
and perhaps be seen as unique and inspired in its presentation. We ask sincerely for feed-
back, general or specific criticism, and suggestions as to how to improve this book, and
thank you for the confidence and trust you have placed in the authors and editors.
Christopher D. Hillyer, MD
Beth H. Shaz, MD
Thomas C. Abshire, MD
James C. Zimring, MD, PhD
Acknowledgments
We, the editors, would like to acknowledge the outstanding technical and profes-
sional support of Sue Rollins, and the expertise and guidance of Megan Wickline and
Mara Conner and other team members at Elsevier. Each of these individuals played
an instrumental role in the creation of this textbook, and we sincerely thank them.
We would like to thank our friends and families for their unconditional love and sup-
port, without which this project could not have come to fruition. We thank especially
Krista, Whitney, Peter, Margot, Jackson and James Hillyer; David, Samara, Jacob and
Andrew Shaz; Kim Jallow and Alexandra Zimring; and Diane, Jonathan, Jennifer, Erin
and Matthew Abshire.
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P A R T I
Blood Banking and Transfusion medicine