Williams Hematology
2528
Transcript of Williams Hematology
Kaushansky_FM_pi_xxii.indd 1 9/21/15 4:40 PM
Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs.
Notice
Williams Hematology
Ninth Edition
Kenneth Kaushansky, MD, MACP Senior Vice President for Health Sciences Dean, School of Medicine SUNY Distinguished Professor Stony Brook University Stony Brook, New York
Josef T. Prchal, MD Professor of Medicine, Pathology, and Genetics Hematology Division University of Utah Salt Lake City, Utah Department of Pathophysiology First Faculty of Medicine Charles University in Prague Prague, Czech Republic
Oliver W. Press, MD, PhD Acting Director, Clinical Research Division Dr. Penny E. Peterson Memorial Chair for Lymphoma
Research Fred Hutchinson Cancer Research Center Professor of Medicine and Bioengineering University of Washington Seattle, Washington
New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto
Marshall A. Lichtman, MD Professor of Medicine and of Biochemistry and Biophysics University of Rochester Medical Center Rochester, New York
Marcel Levi, MD, PhD Professor of Medicine Dean, Faculty of Medicine Academic Medical Center University of Amsterdam Amsterdam, The Netherlands
Linda J. Burns, MD Professor of Medicine Division of Hematology, Oncology and Transplantation University of Minnesota Minneapolis, Minnesota
Michael A. Caligiuri, MD Director, Comprehensive Cancer Center CEO, James Cancer Hospital and Solove Research Institute Professor of Medicine The Ohio State University Columbus, Ohio
Kaushansky_FM_pi_xxii.indd 3 9/21/15 4:40 PM
Copyright © 2016, by McGraw-Hill Education. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher, with the exception that the program listings may be entered, stored, and executed in a computer system, but they may not be reproduced for publication.
ISBN: 978-0-07-183301-1
MHID: 0-07-183301-3
The material in this eBook also appears in the print version of this title: ISBN: 978-0-07-183300-4, MHID: 0-07-183300-5.
eBook conversion by codeMantra Version 1.0
All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps.
McGraw-Hill Education eBooks are available at special quantity discounts to use as premiums and sales promotions or for use in corporate training programs. To contact a representative, please visit the Contact Us page at www.mhprofessional.com.
TERMS OF USE
This is a copyrighted work and McGraw-Hill Education and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill Education’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms.
THE WORK IS PROVIDED “AS IS.” McGRAW-HILL EDUCATION AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill Education and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill Education has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise.
16. Cell-Cycle Regulation and Hematologic Disorders . . . . . . . . . 213 Yun Dai, Prithviraj Bose, and Steven Grant
17. Signal Transduction Pathways. . . . . . . . . . . . . . . . . . . . . . . . . . . 247 Kenneth Kaushansky
18. Hematopoietic Stem Cells, Progenitors, and Cytokines . . . . . 257 Kenneth Kaushansky
19. The Inflammatory Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 Jeffrey S. Warren and Peter A. Ward
20. Innate Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 Bruce Beutler
21. Dendritic Cells and Adaptive Immunity . . . . . . . . . . . . . . . . . . 307 Madhav Dhodapkar, Crystal L. Mackall, and Ralph M. Steinman
PART V
Therapeutic Principles
22. Pharmacology and Toxicity of Antineoplastic Drugs . . . . . . . 315 Benjamin Izar, Dustin Dzube, James M. Cleary, Constantine
S. Mitsiades, Paul G. Richardson, Jeffrey A. Barnes, and Bruce A. Chabner
23. Hematopoietic Cell Transplantation . . . . . . . . . . . . . . . . . . . . . 353 Andrew R. Rezvani, Robert Lowsky, and Robert S. Negrin
24. Treatment of Infections in The Immunocompromised Host. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
Lisa Beutler and Jennifer Babik
25. Antithrombotic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393 Gregory C. Connolly and Charles W. Francis
26. Immune Cell Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409 Carolina Berger and Stanley R. Riddell
27. Vaccine Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421 Katayoun Rezvani and Jeffrey J. Molldrem
28. Therapeutic Apheresis: Indications, Efficacy, and Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Robert Weinstein
29. Gene Therapy for Hematologic Diseases . . . . . . . . . . . . . . . . . . 437 Hua Fung and Stanton Gerson
30. Regenerative Medicine: Multipotential Cell Therapy for Tissue Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447
Jakub Tolar, Mark J Osborn, Randy Daughters, Anannya Banga, and John Wagner
PART VI
The Erythrocyte
31. Structure and Composition of the Erythrocyte . . . . . . . . . . . . 461 Narla Mohandas
32. Erythropoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 Josef T. Prchal and Perumal Thiagarajan
33. Erythrocyte Turnover . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495 Perumal Thiagarajan and Josef Prchal
34. Clinical Manifestations and Classification of Erythrocyte Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
Josef T. Prchal
Clinical Evaluation of the Patient
1. Initial Approach to the Patient: History and Physical Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Marshall A. Lichtman and Linda J. Burns
2. Examination of Blood Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Daniel H. Ryan
3. Examination of The Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Daniel H. Ryan
4. Consultative Hematology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Rondeep S. Brar and Stanley L. Schrier
PART II
5. Structure of the Marrow and the Hematopoietic Microenvironment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Utpal P. Davé and Mark J. Koury
6. The Organization and Structure of Lymphoid Tissues . . . . . . . 85 Aharon G. Freud and Michael A. Caligiuri
PART III
Epochal Hematology
7. Hematology of the Fetus and Newborn . . . . . . . . . . . . . . . . . . . . 99 James Palis and George B. Segel
8. Hematology during Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Martha P. Mims
9. Hematology in Older Persons . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 William B. Ershler, Andrew S. Artz, and Bindu Kanapuru
PART IV
10. Genetic Principles and Molecular Biology . . . . . . . . . . . . . . . . 145 Lynn B. Jorde
11. Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 Lukas D. Wartman and Elaine R. Mardis
12. Epigenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Bradley R. Cairns
13. Cytogenetics and Genetic Abnormalities . . . . . . . . . . . . . . . . . 173 Lucy A. Godley, Madina Sukhanova, Gordana Raca, and
Michelle M. Le Beau
14. Metabolism of Hematologic Neoplastic Cells . . . . . . . . . . . . . . 191 Zandra E. Walton, Annie L. Hsieh, and Chi V. Dang
15. Apoptosis Mechanisms: Relevance to the Hematopoietic System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
John C. Reed
Contentsvi
35. Aplastic Anemia: Acquired and Inherited. . . . . . . . . . . . . . . . . 513 George B. Segel and Marshall A. Lichtman
36. Pure Red Cell Aplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539 Neal S. Young
37. Anemia of Chronic Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .549 Tomas Ganz
38. Erythropoietic Effects of Endocrine Disorders. . . . . . . . . . . . . 559 Xylina T. Gregg
39. The Congenital Dyserythropoietic Anemias. . . . . . . . . . . . . . . 563 Achille Iolascon
40. Paroxysmal Nocturnal Hemoglobinuria . . . . . . . . . . . . . . . . . . 571 Charles J. Parker
41. Folate, Cobalamin, and Megaloblastic Anemias. . . . . . . . . . . . 583 Ralph Green
42. Iron Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 617 Tomas Ganz
43. Iron Deficiency and Overload. . . . . . . . . . . . . . . . . . . . . . . . . . . 627 Tomas Ganz
44. Anemia Resulting from Other Nutritional Deficiencies . . . . . 651 Ralph Green
45. Anemia Associated with Marrow Infiltration . . . . . . . . . . . . . . 657 Vishnu VB Reddy and Josef T. Prchal
46. Erythrocyte Membrane Disorders . . . . . . . . . . . . . . . . . . . . . . . 661 Theresa L Coetzer
47. Erythrocyte Enzyme Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . 689 Wouter W. van Solinge and Richard van Wijk
48. The Thalassemias: Disorders of Globin Synthesis . . . . . . . . . . 725 David J. Weatherall
49. Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities . . . . . . . . . . . . . . . . . . . . . . 759
Kavita Natrajan and Abdullah Kutlar
50. Methemoglobinemia and Other Dyshemoglobinemias . . . . . 789 Archana M. Agarwal and Josef T. Prchal
51. Fragmentation Hemolytic Anemia. . . . . . . . . . . . . . . . . . . . . . . 801 Kelty R. Baker and Joel Moake
52. Erythrocyte Disorders as a Result of Chemical and Physical Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 809
Paul C. Herrmann
Marshall A. Lichtman
54. Hemolytic Anemia Resulting from Immune Injury. . . . . . . . . 823 Charles H. Packman
55. Alloimmune Hemolytic Disease of the Fetus and Newborn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 847
Ross M. Fasano, Jeanne E. Hendrickson, and Naomi L. C. Luban
56. Hypersplenism and Hyposplenism. . . . . . . . . . . . . . . . . . . . . . . 863 Jaime Caro and Srikanth Nagalla
57. Primary and Secondary Erythrocytoses . . . . . . . . . . . . . . . . . . 871 Josef T. Prchal
58. The Porphyrias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 889 John D. Phillips and Karl E. Anderson
59. Polyclonal and Hereditary Sideroblastic Anemias . . . . . . . . . . 915 Prem Ponka and Josef T. Prchal
PART VII
60. Structure and Composition of Neutrophils, Eosinophils, and Basophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 925
C. Wayne Smith
61. Production, Distribution, and Fate of Neutrophils . . . . . . . . . 939 C. Wayne Smith
62. Eosinophils and Related Disorders. . . . . . . . . . . . . . . . . . . . . . . 947 Andrew J. Wardlaw
63. Basophils, Mast Cells, and Related Disorders . . . . . . . . . . . . . . 965 Stephen J. Galli, Dean D. Metcalfe, Daniel A. Arber, and Ann M. Dvorak
64. Classification and Clinical Manifestations of Neutrophil Disorders . .…
Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs.
Notice
Williams Hematology
Ninth Edition
Kenneth Kaushansky, MD, MACP Senior Vice President for Health Sciences Dean, School of Medicine SUNY Distinguished Professor Stony Brook University Stony Brook, New York
Josef T. Prchal, MD Professor of Medicine, Pathology, and Genetics Hematology Division University of Utah Salt Lake City, Utah Department of Pathophysiology First Faculty of Medicine Charles University in Prague Prague, Czech Republic
Oliver W. Press, MD, PhD Acting Director, Clinical Research Division Dr. Penny E. Peterson Memorial Chair for Lymphoma
Research Fred Hutchinson Cancer Research Center Professor of Medicine and Bioengineering University of Washington Seattle, Washington
New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto
Marshall A. Lichtman, MD Professor of Medicine and of Biochemistry and Biophysics University of Rochester Medical Center Rochester, New York
Marcel Levi, MD, PhD Professor of Medicine Dean, Faculty of Medicine Academic Medical Center University of Amsterdam Amsterdam, The Netherlands
Linda J. Burns, MD Professor of Medicine Division of Hematology, Oncology and Transplantation University of Minnesota Minneapolis, Minnesota
Michael A. Caligiuri, MD Director, Comprehensive Cancer Center CEO, James Cancer Hospital and Solove Research Institute Professor of Medicine The Ohio State University Columbus, Ohio
Kaushansky_FM_pi_xxii.indd 3 9/21/15 4:40 PM
Copyright © 2016, by McGraw-Hill Education. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher, with the exception that the program listings may be entered, stored, and executed in a computer system, but they may not be reproduced for publication.
ISBN: 978-0-07-183301-1
MHID: 0-07-183301-3
The material in this eBook also appears in the print version of this title: ISBN: 978-0-07-183300-4, MHID: 0-07-183300-5.
eBook conversion by codeMantra Version 1.0
All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps.
McGraw-Hill Education eBooks are available at special quantity discounts to use as premiums and sales promotions or for use in corporate training programs. To contact a representative, please visit the Contact Us page at www.mhprofessional.com.
TERMS OF USE
This is a copyrighted work and McGraw-Hill Education and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill Education’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms.
THE WORK IS PROVIDED “AS IS.” McGRAW-HILL EDUCATION AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill Education and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill Education has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise.
16. Cell-Cycle Regulation and Hematologic Disorders . . . . . . . . . 213 Yun Dai, Prithviraj Bose, and Steven Grant
17. Signal Transduction Pathways. . . . . . . . . . . . . . . . . . . . . . . . . . . 247 Kenneth Kaushansky
18. Hematopoietic Stem Cells, Progenitors, and Cytokines . . . . . 257 Kenneth Kaushansky
19. The Inflammatory Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279 Jeffrey S. Warren and Peter A. Ward
20. Innate Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 Bruce Beutler
21. Dendritic Cells and Adaptive Immunity . . . . . . . . . . . . . . . . . . 307 Madhav Dhodapkar, Crystal L. Mackall, and Ralph M. Steinman
PART V
Therapeutic Principles
22. Pharmacology and Toxicity of Antineoplastic Drugs . . . . . . . 315 Benjamin Izar, Dustin Dzube, James M. Cleary, Constantine
S. Mitsiades, Paul G. Richardson, Jeffrey A. Barnes, and Bruce A. Chabner
23. Hematopoietic Cell Transplantation . . . . . . . . . . . . . . . . . . . . . 353 Andrew R. Rezvani, Robert Lowsky, and Robert S. Negrin
24. Treatment of Infections in The Immunocompromised Host. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383
Lisa Beutler and Jennifer Babik
25. Antithrombotic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393 Gregory C. Connolly and Charles W. Francis
26. Immune Cell Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409 Carolina Berger and Stanley R. Riddell
27. Vaccine Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421 Katayoun Rezvani and Jeffrey J. Molldrem
28. Therapeutic Apheresis: Indications, Efficacy, and Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Robert Weinstein
29. Gene Therapy for Hematologic Diseases . . . . . . . . . . . . . . . . . . 437 Hua Fung and Stanton Gerson
30. Regenerative Medicine: Multipotential Cell Therapy for Tissue Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447
Jakub Tolar, Mark J Osborn, Randy Daughters, Anannya Banga, and John Wagner
PART VI
The Erythrocyte
31. Structure and Composition of the Erythrocyte . . . . . . . . . . . . 461 Narla Mohandas
32. Erythropoiesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 Josef T. Prchal and Perumal Thiagarajan
33. Erythrocyte Turnover . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 495 Perumal Thiagarajan and Josef Prchal
34. Clinical Manifestations and Classification of Erythrocyte Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
Josef T. Prchal
Clinical Evaluation of the Patient
1. Initial Approach to the Patient: History and Physical Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Marshall A. Lichtman and Linda J. Burns
2. Examination of Blood Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Daniel H. Ryan
3. Examination of The Marrow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Daniel H. Ryan
4. Consultative Hematology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Rondeep S. Brar and Stanley L. Schrier
PART II
5. Structure of the Marrow and the Hematopoietic Microenvironment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Utpal P. Davé and Mark J. Koury
6. The Organization and Structure of Lymphoid Tissues . . . . . . . 85 Aharon G. Freud and Michael A. Caligiuri
PART III
Epochal Hematology
7. Hematology of the Fetus and Newborn . . . . . . . . . . . . . . . . . . . . 99 James Palis and George B. Segel
8. Hematology during Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . 119 Martha P. Mims
9. Hematology in Older Persons . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 William B. Ershler, Andrew S. Artz, and Bindu Kanapuru
PART IV
10. Genetic Principles and Molecular Biology . . . . . . . . . . . . . . . . 145 Lynn B. Jorde
11. Genomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 Lukas D. Wartman and Elaine R. Mardis
12. Epigenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Bradley R. Cairns
13. Cytogenetics and Genetic Abnormalities . . . . . . . . . . . . . . . . . 173 Lucy A. Godley, Madina Sukhanova, Gordana Raca, and
Michelle M. Le Beau
14. Metabolism of Hematologic Neoplastic Cells . . . . . . . . . . . . . . 191 Zandra E. Walton, Annie L. Hsieh, and Chi V. Dang
15. Apoptosis Mechanisms: Relevance to the Hematopoietic System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
John C. Reed
Contentsvi
35. Aplastic Anemia: Acquired and Inherited. . . . . . . . . . . . . . . . . 513 George B. Segel and Marshall A. Lichtman
36. Pure Red Cell Aplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539 Neal S. Young
37. Anemia of Chronic Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .549 Tomas Ganz
38. Erythropoietic Effects of Endocrine Disorders. . . . . . . . . . . . . 559 Xylina T. Gregg
39. The Congenital Dyserythropoietic Anemias. . . . . . . . . . . . . . . 563 Achille Iolascon
40. Paroxysmal Nocturnal Hemoglobinuria . . . . . . . . . . . . . . . . . . 571 Charles J. Parker
41. Folate, Cobalamin, and Megaloblastic Anemias. . . . . . . . . . . . 583 Ralph Green
42. Iron Metabolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 617 Tomas Ganz
43. Iron Deficiency and Overload. . . . . . . . . . . . . . . . . . . . . . . . . . . 627 Tomas Ganz
44. Anemia Resulting from Other Nutritional Deficiencies . . . . . 651 Ralph Green
45. Anemia Associated with Marrow Infiltration . . . . . . . . . . . . . . 657 Vishnu VB Reddy and Josef T. Prchal
46. Erythrocyte Membrane Disorders . . . . . . . . . . . . . . . . . . . . . . . 661 Theresa L Coetzer
47. Erythrocyte Enzyme Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . 689 Wouter W. van Solinge and Richard van Wijk
48. The Thalassemias: Disorders of Globin Synthesis . . . . . . . . . . 725 David J. Weatherall
49. Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities . . . . . . . . . . . . . . . . . . . . . . 759
Kavita Natrajan and Abdullah Kutlar
50. Methemoglobinemia and Other Dyshemoglobinemias . . . . . 789 Archana M. Agarwal and Josef T. Prchal
51. Fragmentation Hemolytic Anemia. . . . . . . . . . . . . . . . . . . . . . . 801 Kelty R. Baker and Joel Moake
52. Erythrocyte Disorders as a Result of Chemical and Physical Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 809
Paul C. Herrmann
Marshall A. Lichtman
54. Hemolytic Anemia Resulting from Immune Injury. . . . . . . . . 823 Charles H. Packman
55. Alloimmune Hemolytic Disease of the Fetus and Newborn . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 847
Ross M. Fasano, Jeanne E. Hendrickson, and Naomi L. C. Luban
56. Hypersplenism and Hyposplenism. . . . . . . . . . . . . . . . . . . . . . . 863 Jaime Caro and Srikanth Nagalla
57. Primary and Secondary Erythrocytoses . . . . . . . . . . . . . . . . . . 871 Josef T. Prchal
58. The Porphyrias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 889 John D. Phillips and Karl E. Anderson
59. Polyclonal and Hereditary Sideroblastic Anemias . . . . . . . . . . 915 Prem Ponka and Josef T. Prchal
PART VII
60. Structure and Composition of Neutrophils, Eosinophils, and Basophils . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 925
C. Wayne Smith
61. Production, Distribution, and Fate of Neutrophils . . . . . . . . . 939 C. Wayne Smith
62. Eosinophils and Related Disorders. . . . . . . . . . . . . . . . . . . . . . . 947 Andrew J. Wardlaw
63. Basophils, Mast Cells, and Related Disorders . . . . . . . . . . . . . . 965 Stephen J. Galli, Dean D. Metcalfe, Daniel A. Arber, and Ann M. Dvorak
64. Classification and Clinical Manifestations of Neutrophil Disorders . .…
