Pathophysiology of Blood Disorders

353 Pages·2011·38.45 MB·English

by  Howard Franklin Bunn

Pathophysiology of
Blood Disorders
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a LANGE medical book
Pathophysiology of
Blood Disorders
H. Franklin Bunn, MD
Professor of Medicine
Harvard Medical School
Hematology Division
Brigham and Women’s Hospital
Boston, Massachusetts
Jon C. Aster, MD, PhD
Professor, Department of Pathology
Harvard Medical School
Staff Pathologist,
Department of Pathology
Brigham and Women’s Hospital
Boston, Massachusetts
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Contents
Contributors vii | Preface ix
1. Introduction to Blood and II
P A R T
Hematopoietic Tissues
Jon C. Aster 1 HEMOSTASIS AND THROMBOSIS 141
2. Hematopoiesis
13. Overview of Hemostasis
David Scadden and Jon C. Aster 14
H. Franklin Bunn and Bruce Furie 142
14. Platelet Disorders
I H. Franklin Bunn and Bruce Furie 157
PA R T
15. Inherited Coagulation Disorders
ANEMIA AND RED CELL
H. Franklin Bunn and Bruce Furie 170
DISORDERS 29
16. Acquired Coagulation Disorders
H. Franklin Bunn and Bruce Furie 179
3. Overview of the Anemias
H. Franklin Bunn 30 17. Thrombotic Disorders
4. Anemias Due to Bone Marrow Failure or H. Franklin Bunn and Kenneth A. Bauer 188
Infiltration
H. Franklin Bunn 42 P A R T III
5. Iron Homeostasis: Deficiency and Overload
WHITE BLOOD CELL
H. Franklin Bunn and Matthew M. Heeney 51
DISORDERS 199
6. Megaloblastic Anemias
H. Franklin Bunn and Matthew Heeney 63
18. Leukocyte Function and Non-malignant
7. Anemias Associated With Chronic Illness Leukocyte Disorders
H. Franklin Bunn 75 Jon C. Aster and Nancy Berliner 200
8. Thalassemia
19. Introduction to Hematologic Malignancies
H. Franklin Bunn and David G. Nathan 81
Jon C. Aster and Mark Fleming 216
9. Sickle Cell Disease
20. Myeloproliferative Disorders and Myelodysplastic
H. Franklin Bunn 95
Syndromes
10. Hemolytic Disorders of the Red Cell Membrane Jon C. Aster and Daniel J. DeAngelo 229
and Red Cell Metabolism
H. Franklin Bunn and Samuel E. Lux 110 21. Acute Leukemias
Jon C. Aster and Daniel J. Deangelo 244
11. Acquired Hemolytic Anemias
H. Franklin Bunn 122 22. Non-Hodgkin Lymphomas and Chronic
Lymphocytic Leukemias
12. Erythrocytosis
Jon C. Aster and Arnold Freedman 260
H. Franklin Bunn 133
v
vi Contents
23. Hodgkin Lymphoma P A R T IV
Jon C. Aster and Arnold Freedman 279
TRANSFUSION MEDICINE 301
24. Multiple Myeloma and
Related Disorders 25. Blood Transfusion
Jon C. Aster 287 H. Franklin Bunn and Richard Kaufman 302
26. Hematopoietic Stem Cell Transplantation
Jon C. Aster and Joseph H. Antin 314
Answers to Questions 325
Index 327
Contributors
Joseph H. Antin, M.D. Bruce Furie, M.D.
Professor of Medicine Professor of Medicine
Dana Farber Cancer Institute Beth Israel Deaconess Medical Center
Boston, Massachusetts Boston, Massachusetts
Kenneth A. Bauer, M.D. Richard M. Kaufman, M.D.
Professor of Medicine Assistant Professor of Pathology
Beth Israel Deaconess Medical Center Medical Director,
Boston, Massachusetts Adult Transfusion Service
Brigham & Women’s Hospital
Nancy Berliner, M.D.
Boston, Massachusetts
Professor of Medicine
Director of Hematology Matthew M Heeney, M.D.
Brigham and Women’s Hospital Assistant Professor of Pediatrics
Boston, Massachusetts Hematology/Oncology Fegan 704
Children’s Hospital Boston
Daniel J. DeAngelo, M.D., Ph.D.
Boston, Massachusetts
Associate Professor of Medicine
Dana Farber Cancer Institute Samuel E. Lux IV, M.D.
Boston, Massachusetts Professor of Pediatrics
Division of Hematology/Oncology
Mark D. Fleming, M.D., Ph.D.
Children’s Hospital Boston
Professor of Pathology
Boston, Massachusetts
Children’s Hospital Boston
Boston, Massachusetts David G. Nathan, M.D.
Professor of Pediatrics
Arnold S. Freedman, M.D.
Dana Farber Cancer Institute
Associate Professor of Medicine
Boston, Massachusetts
Department of Medical Oncology
Division of Hematologic Malignancies David T. Scadden, M.D.
Dana-Farber Cancer Institute Professor of Medicine
Boston, Massachusetts Center for Regenerative Medicine
Boston, Massachusetts
vii
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CHAPTER 8 Th alassemia ix
Preface
Th e study of blood and hematologic disorders has in this course, and many of the fi gures have been taken
special appeal for medical students as well as phy- directly or adapted from their lectures. We wrote the
sicians at all stages of their training. Few specialties fi rst draft s of all the co-authored chapters and revised
have such a broad impact on other medical disci- them following in-depth input from our colleagues.
plines. A competent hematologist must be well- Moreover, each of us provided thorough reviews of
grounded in pathology, internal medicine, pediatrics, the others’ chapters. All fi gures in this book were
and surgery. Conversely, both generalists and other redrawn by a single artist and vetted by both of us.
specialists regularly encounter patients with anemia, We hope that these measures have enabled our book
hemorrhage, thrombosis, and hematologic malignan- to achieve uniformity of style and clarity along with a
cies. For many students, the close kinship of hematol- high level of scientifi c rigor and clinical relevance.
ogy with laboratory medicine is an added virtue. Few We are indebted to a number of individuals who
medical disciplines enjoy such a rich array of reliable helped bring our book to fruition. James Shanahan,
and informative diagnostic tests, and none has stron- Karen Edmonson, and Armen Ovsepyan at McGraw-
ger underpinnings in contemporary molecular and Hill provided critical editorial advice including guid-
cell biology and molecular pathology. ance on how to make the book useful and interesting to
Our book is designed to introduce medical stu- students. Jessica Hughes and Muriel Goutas provided
dents to the physiological principles underlying the invaluable secretarial help. Dr. Jeff Kutok (Brigham
regulation and function of blood cells and hemo- and Women’s Hospital) and Carola von Kapff con-
stasis as well as the pathophysiologic mechanisms tributed images of some of the peripheral smears
responsible for the development of blood disorders. used in the book. About 10 months prior to publica-
We have placed more emphasis on principles than tion, a draft of this book was provided to 180 Harvard
on practice. Accordingly, we have avoided technical medical students, class of 2012. Many were remarkably
details pertaining to diagnostic tests and procedures conscientious and astute in picking up technical as well
as well as the compilation of specifi c drugs and dos- as conceptual errors. We are grateful for their input,
ages. Instead, issues pertaining to diagnosis and man- which improved the fi nal version of the book substan-
agement are covered primarily within a framework of tially. Finally, we thank our wives, Erin Malone and
pathogenesis. Betsy Bunn for their love and support.
Th e organization and contents of the book are
H. Franklin Bunn
based on a 3-week hematology course given to stu-
Jon C. Aster
dents in their second year at Harvard Medical School.
August 2010
All of the authors of individual chapters are lecturers
ix