Hematological Complications in Obstetrics, Pregnancy, and
Gynecology 1st Edition
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Hematological Complications
in Obstetrics, Pregnancy,
and Gynecology
Edited by
Rodger L. Bick (Editor in Chief )
University of Texas Southwestern Medical Center, Dallas, Texas, USA
Eugene Frenkel (Editor)
Harold C. Simmons Comprehensive Cancer Center, Dallas, Texas, USA
William Baker (Editor)
Thrombosis Center, Bakersfield, California, USA
and
Ravindra Sarode (Editor)
University of Texas Southwestern Medical Center, Dallas, Texas, USA
CAMBRIDGE UNIVERSITY PRESS
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
www.cambridge.org
Information on this title: www.cambridge.org/9780521839532
# Cambridge University Press 2006
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 2006
Printed in the United Kingdom at the University Press, Cambridge
A catalog record for this publication is available from the British Library
ISBN-13 978-0-521-83953-2 hardback
ISBN-10 0-521-83953-X 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 book to provide accurate and up-to-date information which is
in accord with accepted standards and practice at the time of publication. Although case histories are drawn
from actual cases, every effort has been made to disguise the identities of the individuals involved.
Nevertheless, the authors, editors and publishers 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 publishers therefore disclaim all liability for direct or consequential
damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful
attention to information provided by the manufacturer of any drugs or equipment that they plan to use.
This textbook is dedicated to the important women in my life:
To my daughters, Shauna Nicole Bick and Michelle Leanne Gage
To the memory of my late wife, Marcella Ann Bick
And to:
All the hundreds of women with complications of pregnancy
and their subsequent children whom I have had the privilege of
caring for – this experience has been the most gratifying of my
entire medical career.
Contents
List of contributors page ix
Preface xi
1 Disseminated intravascular coagulation in obstetrics, pregnancy,
and gynecology: Criteria for diagnosis and management 1
Rodger L. Bick and Deborah Hoppensteadt
2 Recurrent miscarriage syndrome and infertility caused by blood
coagulation protein/platelet defects 55
Rodger L. Bick
3 Von Willebrand disease and other bleeding disorders in obstetrics 75
Franklin Fuda and Ravindra Sarode
4 Hemolytic disease of the fetus and newborn caused by ABO, Rhesus,
and other blood group alloantibodies 103
Katharine A. Downes and Ravindra Sarode
5 Hereditary and acquired thrombophilia in pregnancy 122
Rodger L. Bick and William F. Baker
6 Thromboprophylaxis and treatment of thrombosis in pregnancy 200
L. Heilmann, W. Rath and R. L. Bick
7 Diagnosis of deep vein thrombosis and pulmonary embolism
in pregnancy 222
William F. Baker, Eugene P. Frenkel and Rodger L. Bick
8 Hemorrhagic and thrombotic lesions of the placenta 250
Raymond W. Redline
viii Contents
9 Iron deficiency, folate, and vitamin B12 deficiency in pregnancy,
obstetrics, and gynecology 269
William F. Baker and Ray Lee
10 Thrombosis prophylaxis and risk factors for thrombosis in
gynecologic oncology 310
Georg-Friedrich von Tempelhoff
11 Low molecular weight heparins in pregnancy 341
Debra A. Hoppensteadt, Jawed Fareed, Harry L. Messmore, Omer Iqbal,
William Wehrmacher and Rodger L. Bick
12 Post partum hemorrhage: Prevention, diagnosis, and management 361
William F. Baker, Joseph Mansour and Arthur Fontaine
13 Hemoglobinopathies in pregnancy 442
Adeboye H. Adewoye and Martin H. Steinberg
14 Genetic counseling and prenatal diagnosis 469
Karen Heller and Robyn Horsager
15 Thrombocytopenia in pregnancy 490
Ravindra Sarode and Eugene P. Frenkel
16 Neonatal immune thrombocytopenias 506
Katharine A. Downes and Ravindra Sarode
17 The rational use of blood and its components in obstetrical and
gynecological bleeding complications 528
Katharine A. Downes and Ravindra Sarode
18 Heparin-induced thrombocytopenia in pregnancy 556
Barbara B. Haley, Rodger L. Bick and Eugene P. Frenkel
19 Coagulation defects as a cause for menstrual disorders 570
Albert J. Phillips
Index 589
Contributors
Adeboye H. Adewoye Arthur Fontaine
Assistant Professor of Medicine, Chairman of Radiology, Mercy Hospital,
Department of Medicine, Section of 2215 Truxtun Ave., Bakersfield,
Hematology-Oncology and the Center of CA 93301, USA
Excellence in Sickle Cell Disease, Boston
Medical Center, Boston, MA 02118, USA Eugene P. Frenkel
[email protected] Professor of Medicine and Radiology,
Harold C. Simmons Comprehensive
William F. Baker Jr. Cancer Center, University of Texas
Center for Health Sciences, David Geffen Southwestern Medical School, 2201
School of Medicine at University of Inwood Road, Dallas, TX 75235-8852, USA
California-Los Angeles, Los Angeles, CA, USA
[email protected]Rodger L. Bick Franklin Fuda
Department of Medicine, University of Fellow, Department of Pathology, UT
Texas Southwestern Medical Center, Southwestern Medical Center, 5323 Harry
Dallas Thrombosis Hemostasis Clinical Hines Blvd., Dallas, TX 75390-9073, USA
Center, 10455 North Central Expressway,
Suite 109, PMB 320, Dallas, TX 75231, USA Barbara B. Haley
[email protected] Professor of Medicine, Sherry Wigley
Crow Cancer Research Endowed Chair
Katharine Downes in Honor of Robert Lewis Kirby, M.D.,
Assistant Professor, Department of University of Texas Southwestern Medical
Pathology, University Hospitals of School, 5323 Harry Hines Blvd., Dallas,
Cleveland, Cleveland, OH, USA TX 75390-8852, USA
Jawed Fareed Lothar Heilmann
Professor of Pathology and Pharmacology, Department of Obstetrics and Gynecology,
Loyola University Chicago, Maywood, City Hospital, August-Bebel-Str. 59, 65428
Illinois, USA Russelsheim, Germany
[email protected] x List of contributors
Karen Heller Albert J. Phillips
Faculty Associate, Department of Pathology, Clinical Professor of Obstetrics and
University of Texas Southwestern Medical Gynecology, University of Southern
Center, Dallas, Texas, USA California, School of Medicine, 1301 20th
Street, Suite 270, Santa Monica, CA 90404, USA
Debra A. Hoppensteadt
[email protected] Department of Pathology, Loyola
University Medical Center, 2160 S. First Werner Rath
Ave., Maywood, Illinois, USA Department of Obstetrics and Gynecology,
[email protected] University of Aachen, 52057 Aachen, Germany
Robyn Horsager Raymond W. Redline
Associate Professor, Division of Maternal Department of Pathology, University
Fetal Medicine, Department of Obstetrics Hospitals of Cleveland, 11100 Euclid
and Gynecology, University of Texas Avenue, Cleveland, OH 44106, USA
Southwestern Medical Center, Dallas,
TX, USA Ravindra Sarode
Professor, Department of Pathology, UT
Omer Iqbal Southwestern Medical Center, 5323 Harry
Research Assistant Professor, Department Hines Blvd., CS3.114, Dallas,
of Pathology, Loyola University Chicago, TX 75390-9073, USA
Maywood, Illinois, USA
Martin H. Steinberg
Ray Lee Professor of Medicine, Pediatrics,
Associate Professor of Internal Medicine Pathology and Laboratory Medicine,
University of Texas Southwestern School Department of Medicine, Section of
of Medicine, 5323 Harry Hines Blvd., Hematology-Oncology and the Center of
Dallas, TX 75390-8889, USA Excellence in Sickle Cell Disease, Boston
[email protected] Medical Center, Boston, MA 02118, USA
Joseph Mansour Georg-Friedrich von Tempelhoff
Associate Professor, Department of GP Rüsselsheim, Department of Obstetrics
Obstetrics and Gynecology, Kern Medical and Gynecology, August Bebel Strasse 59
Center, 1830 Flower St., Bakersfield, CA 65428 Rüsselsheim, Germany
93305, USA
[email protected] Harry L. Messmore William Wehrmacher
Professor Emeritus, Department of Professor Emeritus, Department of
Medicine, Loyola University Chicago, Physiology, Loyola University Chicago,
Maywood, Illinois, USA Maywood, Illinois, USA
Preface
Hematological complications of obstetrics, pregnancy and gynecology are many,
and, unfortunately, often lead to significant morbidity or mortality for both
mother and child, for example disseminated intravascular coagulation, amniotic
fluid embolism or postoperative deep vein thrombosis/pulmonary embolus, not
only in obstetrical patients but also common in postoperative gynecological
patients – particularly those having surgery for a malignancy. These complications
range from hemorrhagic complications, thrombotic complications, combinations
(such as disseminated intravascular coagulation), various anemias, hemoglobino-
pathies and others. A textbook on this topic was last written in the 1970s, and for
the past several decades, hematologists, obstetricians, gynecologists, reproductive
medicine specialists, internists, anesthesiologists and others have had to rely upon
research reports, small clinical trials, opinion, rare review articles and very brief
chapters in obstetrical and gynecological textbooks. An additional problem is that
busy specialists in the aforementioned areas have a difficult time keeping up with a
logarithmic increase in medical information relative to their particular areas.
Thus, we have compiled a textbook, written by experienced experts in the various
aspects of hematological complications of obstetrics, pregnancy and gynecology to
serve as a ready reference for practicing physicians in these specialties to quickly
find information relative to these problems. In each instance, where appropriate,
the etiology, pathophysiology, clinical and laboratory diagnosis and management
are discussed. It is hoped this text will help the practicing specialists caring for
women with these hematological complications of pregnancy and the end result
will be improved understanding, improved diagnosis, improved principles of
management, and enhanced morbidity and mortality for these too often cata-
strophic problems.
1
Disseminated intravascular coagulation in
obstetrics, pregnancy, and gynecology: Criteria
for diagnosis and management
Rodger L. Bick, M.D., Ph.D., F.A.C.P.1 and
Deborah Hoppensteadt, Ph.D., D.I.C.2
1
Clinical Professor of Medicine and Pathology, University of Texas Southwestern Medical Center, Director: Dallas
Thrombosis Hemostasis and Vascular Medicine Clinical Center, Dallas, Texas, USA
2
Associate Professor of Pathology, Loyola University Medical Center, Maywood, Illinois, USA
Syndromes of disseminated intravascular coagulation
in obstetrics, pregnancy and gynecology
Objective criteria for diagnosis and management
Introduction
Disseminated intravascular coagulation is a confusing syndrome, regarding diag-
nostic and therapeutic modalities. Confusion and controversy stem from (1) the
fact that many unrelated clinical scenario may induce DIC (2) a lack of uniformity
in clinical manifestations (3) confusion regarding appropriate laboratory diagno-
sis and (4) unclear guidelines for management with respect to specific therapeutic
modalities potentially available. Recommendations for and evaluation of manage-
ment becomes even more difficult because: (1) the morbidity and survival is often
dependent on the specific cause of DIC and (2) few of the generally used specific
modes of therapy, heparin, antithrombin concentrate, protein C concentrate, and
others, have been subjected to objective prospective randomized trials, except
antithrombin concentrates.
This chapter provides specific and objective guidelines and criteria for (1) the
clinical diagnosis, (2) laboratory diagnosis, and (3) to provide objective systems to
assess efficacy of any given specific therapeutic modality, independent of influences
of the underlying (inducing) disease causing the DIC in obstetrical, pregnancy or
gynecological patients.1,2 This approach allows for objective decisions regarding
diagnosis and management in particular obstetric and gynecological settings and in
Hematological Complications in Obstetrics, Pregnancy, and Gynecology, ed. R. L. Bick et al. Published by
Cambridge University Press. # Cambridge University Press 2006.
2 Rodger L. Bick and Deborah Hoppensteadt
individual patients. A general review of the etiology, pathophysiology, clinical and
laboratory diagnosis, and management modalities suggested for DIC in obstetrics
and gynecology is provided.
Disseminated intravascular coagulation (DIC) is an intermediary mechanism of
disease usually seen in association with well-defined clinical disorders.3,4,5,6 In
obstetrics, pregnancy and gynecology, those disorders include amniotic fluid
embolism, placental abruption, missed abortion, retained fetus syndrome, pla-
centa previa (occasionally), preeclampsia/eclampsia, HELLP syndrome, ovarian
cancer, uterine cancer and breast cancer. Of course, as will be discussed, the
obstetric and gynecologic patient may also develop DIC secondary to other
medical and surgical complications not specifically unique to obstetrics, preg-
nancy and gynecology, for example inflammation, infection, sepsis, etc.
The pathophysiology of DIC serves as an intermediary mechanism in many disease
processes, which sometimes remain organ specific. This catastrophic syndrome
spans all areas of medicine and presents a broad clinical spectrum that is confusing
to many. DIC was called ‘‘consumptive coagulopathy’’ in early literature;7,8 this
is no longer an adequate description as very little is consumed in DIC; most
factors and plasma constituents are plasmin biodegraded. Terminology following
this phrase was ‘‘defibrination syndrome’’. The modern term is disseminated intra-
vascular coagulation; this is a beneficial descriptive pathophysiological term if
one accepts the concept that ‘‘coagulation’’ is expressed as both hemorrhage and
thrombosis.1,3,4,5,6 Most physicians consider DIC to be a systemic hemorrhagic
syndrome however, this is only because hemorrhage is obvious and often impressive.
Less commonly appreciated is the formidable microvascular thrombosis and
sometimes, large vessel thrombosis occurring. The hemorrhage is often simple to
contend with in patients with fulminant DIC but it is the small and large vessel
thrombosis, with impairment of blood flow, ischemia, and associated end-organ
damage that usually leads to irreversible morbidity and mortality. Throughout this
review, fulminant DIC versus ‘‘low-grade’’ compensated DIC and the attendant
Table 1.1 Definition of disseminated intravascular coagulation (minimal acceptable criteria).
A systemic thrombohemorrhagic disorder seen in association with well-defined
clinical situations
and
Laboratory evidence of
(1) Procoagulant activation
(2) Fibrinolytic activation
(3) Inhibitor consumption and
(4) Biochemical evidence of end-organ damage or failure
3 Disseminated intravascular coagulation in obstetrics
differences in clinical manifestations, laboratory findings, and treatment are
discussed. However, these are often pure and theoretical, clinical spectrums of a
disease continuum; patients may present anywhere in this continuum and may lapse
from one end of the spectrum into another. A clear definition of DIC is outlined in
Table 1.1.
Historical perspectives
The first description of disseminated intravascular coagulation comes from a
lecture delivered by Dr. Walter H. Seegers titled ‘‘Factors in the Control of
Bleeding’’.9 Major clinical extensions of this early observation were shortly
reported thereafter by Dr’s. Ratnoff, Pritcher, and Colopy in an article entitled
‘‘Hemorrhagic States During Pregnancy.’’10,11 In this two part article, many
important observations were described including recognition that the hemorrhagic
syndromes of pregnancy, now called DIC, included premature separation of the
placenta, amniotic fluid embolism, the presence of a dead fetus in utero and severe
pre-eclampsia or overt toxemia of pregnancy. Subsequently, more reports and
descriptions of disseminated intravascular coagulation began to appear and in the
mid-1960’s, DIC became a clinically accepted and recognized syndrome. We owe
our basic understanding and appreciation of this syndrome to the astute clinical
and laboratory observations of Dr. Walter H. Seegers and Dr. Oscar D. Ratnoff and
their co-workers.
Etiology
DIC is usually seen in association with well-defined clinical entities.1,2,3,4,5,6,12,13
Those clinical disorders specific for obstetrics and gynecology are found in
Table 1.2. The clinical disorders common to all medical specialties, and sometimes
complicating the course of an obstetrical or gynecological patient and inducing to
DIC are summarized in Table 1.3.
DIC syndromes unique to pregnancy and obstetrics
Obstetrical accidents are common events leading to disseminated intravascular
coagulation. Amniotic fluid embolism with DIC is the most catastrophic and
common of the life threatening obstetrical accidents.1,2,4,5,6,7
The syndrome of amniotic fluid embolism (AFE) is manifest by the acute onset
of respiratory failure, circulatory collapse, shock and the serious thrombohemor-
rhagic syndrome of disseminated intravascular coagulation (DIC). The first care-
ful description of this syndrome was by Steiner and Lushbaugh in 1941;14 in
