vip.persianss.ir vip.persianss.ir Unless otherwise noted, data for reference interval tables were compiled from multiple sources and may vary slightly from intervals listed within chapters. Each laboratory must establish its particular intervals based on its instrumentation, meth - odology and demographics of the population it serves. Hematology/Hemostasis Reference Intervals COMPLETE BLOOD COUNT REFERENCE INTERVALS (ADULT) Assay Units Reference Intervals RBC, male 3 10 6 /μL ( 3 10 12 /L) 4.20–6.00 RBC, female 3 10 6 /μL ( 3 10 12 /L) 3.80–5.20 HGB, male g/dL (g/L) 13.5–18.0 (135–180) HGB, female g/dL (g/L) 12.0–15.0 (120–150) HCT, male % (L/L) 40–54 (0.40–0.54) HCT, female % (L/L) 35–49 (0.35–0.49) MCV fL 80–100 MCH pg 26–34 MCHC g/dL 32–36 RDW % 11.5–14.5 RETIC 3 10 3 /μL ( 3 10 9 /L) 20–115 RETIC % 0.5–2.5 NRBC /100 WBC 0 WBC 3 10 3 /μL ( 3 10 9 /L) 3.6–10.6 NEUT % 50–70 NEUT (ANC) 3 10 3 /μL ( 3 10 9 /L) 1.7–7.5 LYMPH % 18–42 LYMPH 3 10 3 /μL ( 3 10 9 /L) 1.0–3.2 MONO % 2–11 MONO 3 10 3 /μL ( 3 10 9 /L) 0.1–1.3 EO % 1–3 EO 3 10 3 /μL ( 3 10 9 /L) 0–0.3 BASO % 0–2 BASO 3 10 3 /μL ( 3 10 9 /L) 0–0.2 PLT 3 10 3 /μL ( 3 10 9 /L) 150–450 MPV fL 7.0–12.0 Assay Units Reference Intervals ESR, male (Westergren) mm 1 hour 0–15 (0 2 50 y) 0–20 ( 50 y) Serum iron μg/dL 50–160 Total iron-binding capacity μg/dL 250–400 Transferrin saturation % 20–55 Serum ferritin, male ng/mL 40–400 Serum ferritin, female ng/mL 12–160 ESR, female (Westergren) mm 1 hour 0–20 (0 2 50 y) 0–30 ( 50 y) Serum vitamin B 12 pg/mL 200–900 Serum folate ng/mL 4.0 RBC folate ng/mL 120 Haptoglobin mg/dL 30–200 Free serum hemoglobin mg/dL 0–10 HEMOGLOBIN FRACTION REFERENCE INTERVALS Fraction Adult Reference Intervals (%) Newborn Reference Intervals (%) Hb A 95 10–40 Hb F 0–2.0 60–90 Hb A 2 0–3.5 Assay Units Reference Intervals REFERENCE INTERVALS FOR OTHER COMMONLY ORDERED TESTS (ADULTS) Assay Units Reference Intervals vip.persianss.ir COMPLETE BLOOD COUNT REFERENCE INTERVALS (PEDIATRIC) BONE MARROW ASPIRATE REFERENCE INTERVALS (ADULT) WBC Differential Reference Intervals (%) Erythrocyte Series Reference Intervals (%) Blasts 0–3 Promyelocytes 1–5 Pronormoblasts 0–1 N. myelocytes 6–17 Basophilic NB 1–4 N. metamyelocytes 3–20 Polychromatophilic NB 10–20 N. bands 9–32 Orthochromic NB 6–10 N. segmented (polymorphonuclear) 7–30 Eosinophils 0–3 Other Basophils 0–1 M:E ratio 1.5–3.3:1 Lymphocytes 5–18 Megakaryocytes 2–10/lpf Plasma cells 0–1 Monocytes 0–1 Histiocytes (macrophages) 0–1 Assay Units 0–1 d 2–4 d 5–7 d 8–14 d 15–30 d 1–2 mo 3–5 mo 6–11 mo 1–3 y 4–7 y 8–13 y RBC 3 10 6 /μL ( 3 10 12 /L) 4.10–6.10 4.36–5.96 4.20–5.80 4.00–5.60 3.20–5.00 3.40–5.00 3.65–5.05 3.60–5.20 3.40–5.20 4.00–5.20 4.00–5.40 HGB g/dL (g/L) 16.5–21.5 (165–215) 16.4–20.8 (164–208) 15.2–20.4 (152–204) 15.0–19.6 (150–196) 12.2–18.0 (122–180) 10.6–16.4 (106–164) 10.4–16.0 (104–160) 10.4–15.6 (104–156) 9.6–15.6 (96–156) 10.2–15.2 (102–152) 12.0–15.0 (120–150) HCT % 48–68 48–68 50–64 46–62 38–53 32–50 35–51 35–51 34–48 36–46 35–49 MCV fL 95–125 98–118 100–120 95–115 93–113 83–107 83–107 78–102 76–92 78–94 80–94 MCH pg 30–42 30–42 30–42 30–42 28–40 27–37 25–35 23–31 23–31 23–31 26–32 MCHC g/dL 30–34 30–34 30–34 30–34 30–34 31–37 32–36 32–36 32–36 32–36 32–36 RDW % * * * * * * * 11.5–14.5 11.5–14.5 11.5–14.5 11.5–14.5 RETIC % 1.8–5.8 1.3–4.7 0.2–1.4 0–1.0 0.2–1.0 0.8–2.8 0.5–1.5 0.5–1.5 0.5–1.5 0.5–1.5 0.5–1.5 RETIC 3 10 3 /μL ( 3 10 9 /L) 73.8–353.8 56.7–280.1 8.4–81.2 0.0–56.0 6.4–50.0 27.2–140.0 18.3–75.8 18.0–78.0 17.0–78.8 20–78.0 20–124.2 NRBC /100 WBC 2–24 5–9 0–1 0 0 0 0 0 0 0 0 WBC 3 10 3 /μL ( 3 10 9 / L) 9.0–37.0 8.0–24.0 5.0–21.0 5.0–21.0 5.0–21.0 6.0–18.0 6.0–18.0 6.0–18.0 5.5–17.5 5.0–17.0 4.5–13.5 NEUT (ANC) 3 10 3 /μL ( 3 10 9 /L) 3.7–30.0 2.6–17.0 1.5–12.6 1.2–11.6 1.0–9.5 1.2–8.1 1.1–7.7 1.2–8.1 1.2–8.9 1.5–11.0 1.6–9.5 LYMPH 3 10 3 /μL ( 3 10 9 /L) 1.6–14.1 1.3–11.0 1.2–11.3 1.5–13.0 2.1–12.8 2.5–13.0 2.7–13.5 2.9–14.0 2.0–12.8 1.5–11.1 1.0–7.2 MONO 3 10 3 /μL ( 3 10 9 /L) 0.1–4.4 0.2–3.4 0.2–3.6 0.2–3.6 0.1–3.2 0.2–2.5 0.1–2.0 0.1–2.0 0.1–1.9 0.1–1.9 0.1–1.5 EO 3 10 3 /μL ( 3 10 9 /L) 0.0–1.5 0.0–1.2 0.0–1.3 0.0–1.1 0.0–1.1 0.0–0.7 0.0–0.7 0.0–0.7 0.0–0.7 0.0–0.7 0.0–0.5 BASO 3 10 3 /μL ( 3 10 9 /L) 0.0–0.7 0.0–0.5 0.0–0.4 0.0–0.4 0.0–0.4 0.0–0.4 0.0–0.4 0.0–0.4 0.0–0.4 0.0–0.3 0.0–0.3 PLT 3 10 3 /μL ( 3 10 9 /L) 150–450 150–450 150–450 150–450 150–450 150–450 150–450 150–450 150–450 150–450 150–450 *The RDW is markedly elevated in newborns, with a range of 14.2% to 19.9% in the first few days of life, gradually decreasing until it reaches adult levels by 6 months of age. Pediatric reference intervals are from Riley Hospital for Children, Indiana University Health, Indianapolis, IN. Some reference intervals are listed in common units and in international system of units (SI units) in parenthesis. ANC , absolute neutrophil count (includes segmented neutrophils and bands); BAND , neutrophil bands; BASO , basophils; d , days ; EO , eosinophils; ESR , erythrocyte sedimentation rate; Hb , hemoglobin fraction; HCT, hematocrit; HGB, hemoglobin; lpf, low power field; LYMPH , lymphocytes; MCH, mean cell hemoglobin; MCHC, mean cell hemoglobin concentration; MCV , mean cell volume; M:E, myeloid:erythroid ; mo, month; MONO , monocytes; MPV , mean platelet volume; N, neutrophilic; NB, normoblast; NEUT , neutrophils; NRBC , nucleated red blood cells; PLT , platelets; RBC , red blood cells; RDW, red blood cell distribution width; RETIC , reticulocytes; WBC , white blood cells; y , year. Please see inside back cover for additional reference interval tables. vip.persianss.ir Hematology CLINICAL PRINCIPLES AND APPLICATIONS RODAK’S vip.persianss.ir Activate the complete learning experience that comes with each textbook purchase by registering at http://evolve.elsevier.com/Keohane/ REGISTER TODAY! You can now purchase Elsevier products on Evolve! Go to evolve.elsevier.com/html/shop-promo.html to search and browse for products. YOU’VE JUST PURCHASED MORE THAN A TEXTBOOK! Evolve Student Resources for Keohane: Rodak’s Hematology: Clinical Principles and Practice, 5 th Edition, include the following: • Glossary vip.persianss.ir Hematology RODAK’S Elaine M. Keohane , PhD, MLS Chair and Professor, Department of Clinical Laboratory Sciences School of Health Related Professions Rutgers, The State University of New Jersey Newark, New Jersey Larry J. Smith , PhD, SH(ASCP), HCLD/CC(ABB) Assistant Attending Scientist and Director, Coagulation Laboratory Department of Laboratory Medicine Memorial Sloan-Kettering Cancer Center New York, New York Adjunct Professor, Department of Health Professions York College, The City University of New York Jamaica, New York Adjunct Associate Professor, Department of Clinical Laboratory Sciences School of Health Related Professions Rutgers, The State University of New Jersey Newark, New Jersey CLINICAL PRINCIPLES AND APPLICATIONS Fifth Edition Jeanine M. Walenga , PhD, MT(ASCP) Professor, Thoracic-Cardiovascular Surgery, Pathology, and Physiology Co-Director, Hemostasis and Thrombosis Research Unit Stritch School of Medicine Loyola University Chicago Maywood, Illinois Director, Clinical Coagulation Core Laboratory and Special Coagulation Laboratory Director, Urinalysis and Medical Microscopy Associate Director, Point of Care Testing Loyola University Hospital Maywood, Illinois vip.persianss.ir 3251 Riverport Lane St. Louis, Missouri 63043 RODAK’S HEMATOLOGY: CLINICAL PRINCIPLES AND APPLICATIONS, FIFTH EDITION ISBN: 978-0-323-23906-6 Copyright © 2016, 2012, 2007, 2002, 1995 by Saunders, an imprint of Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. The Publisher ISBN: 978-0-323-23906-6 Executive Content Strategist: Kellie White Content Development Manager: Laurie Gower Content Development Specialist: Rebecca Corradetti Publishing Services Manager: Julie Eddy Project Manager: Sara Alsup Design Direction: Teresa McBryan Text Designer: Ashley Miner Printed in Canada Last digit is the print number: 9 8 7 6 5 4 3 2 1 vip.persianss.ir To my students for being great teachers, and to Camryn, Riley, Harper, Stella, Jackie, Alana, Ken, and Jake for reminding me about the important things in life. EMK To my wonderful mentors and students who have taught me so much about laboratory medicine. LJS To my teachers, both formal and informal, for all this fascinating knowledge in clinical laboratory sciences which made possible my interesting career. JMW vip.persianss.ir Special Dedication To Bernadette “Bunny” F. Rodak , with great admiration and gratitude for your vision, perseverance, and courage to first publish Hematology: Clinical Principles and Applications in 1995; for your over 20-year commitment to publish the highest quality text through five editions; for your mentorship and guidance of five co-editors and over 50 authors; and for sharing your great enthusiasm for hematology and hemostasis and lifelong learning that has inspired a generation of students and faculty in this country and around the world. Special Acknowledgment To George A. Fritsma , with our sincere gratitude for your dedication and reasoned approach that has kept Hematology: Clinical Principles and Applications at the leading edge as a comprehensive, state-of-the-art, yet practical textbook, guided by you as co-editor for two editions and through the multiple number of chapters that you have authored. We are indebted to you for sharing your vast knowledge in hematology and hemostasis and for your unwavering commitment to the profession of clinical laboratory science. vip.persianss.ir vii Reviewers Keith Bellinger, PBT(ASCP) Medical Technologist The United States Department of Veterans Affairs New Jersey Health Care System East Orange, New Jersey; Adjunct Assistant Professor, Clinical Laboratory Sciences Rutgers, The State University of New Jersey Newark, New Jersey Susan Conforti, EdD, MLS(ASCP)SBB Associate Professor, Medical Laboratory Technology Farmingdale State College Farmingdale, New York Shamina Davis, MS, MT(ASCP) Faculty, College of Biomedical Sciences and Health Professions University of Texas at Brownsville Brownsville, Texas Kathleen Doyle, PhD, M(ASCP), MLS(ASCP) CM Medical Laboratory Scientist, Consultant Professor Emeritus, Clinical Laboratory and Nutritional Sciences University of Massachusetts Lowell Lowell, Massachusetts Michele Harms, MS, MLS(ASCP) Program Director, School of Medical Technology WCA Hospital Jamestown, New York Jeanne Isabel, MS, MT(ASCP), CLSpH(NCA) Associate Professor and Program Director, Allied Health and Communicative Disorders Northern Illinois University DeKalb, Illinois Steve Johnson, MS, MT(ASCP) Program Director, School of Medical Technology Saint Vincent Health Center Erie, Pennsylvania Haywood B. Joiner, Jr., EdD, MT(ASCP) Chair, Department of Allied Health Louisiana State University at Alexandria Alexandria, Louisiana Amy R. Kapanka, MS, MT(ASCP)SC MLT Program Director Hawkeye Community College Waterloo, Iowa Linda Kappel, MLT(FCP, CAET) Instructor, Medical Diagnostics Saskatchewan Polytechnic, Saskatoon Campus Saskatoon, Saskatchewan, Canada Linda J. McCown, PhD, MLS(ASCP) CM Chair and Program Director, Clinical Laboratory Science University of Illinois Springfield Springfield, Illinois Christine Nebocat, MS, MT(ASCP) CM Assistant Professor Farmingdale State College Farmingdale, New York Tania Puro, CLS, MS, MT(ASCP) Instructor, Clinical Lab Science Program San Francisco State University San Francisco, California vip.persianss.ir viii Contributors Sameer Al Diffalha, MD Pathology Resident PGY3 Loyola University Medical Center Maywood, Illinois Larry D. Brace, PhD, MT(ASCP)SH Clinical Pathology/Laboratory Consultant Emeritus Professor of Pathology University of Illinois at Chicago Chicago, Illinois; Scientific Director of Laboratories Laboratory and Pathology Diagnostics at Edward Hospital Naperville, Illinois Karen S. Clark, BS, MT(ASCP)SH Point of Care Manager Baptist Memorial Hospital Memphis, Tennessee Magdalena Czader, MD, PhD Director, Division of Hematopathology Director, Clinical Flow Cytometry Laboratory Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis, Indiana Kathryn Doig, PhD, MLS(ASCP) CM SH(ASCP) CM Professor, Biomedical Laboratory Diagnostics College of Natural Science Michigan State University East Lansing, Michigan Sheila A. Finch, CHSP, CHMM, MS, BS, MT(ASCP) Executive Director, Environment of Care/Emergency Management Detroit Medical Center Detroit, Michigan George A. Fritsma, MS, MLS Manager The Fritsma Factor, Your Interactive Hemostasis Resource Birmingham, Alabama Margaret G. Fritsma, MA, MT(ASCP)SBB Associate Professor, Retired School of Health Professions Division of Laboratory Medicine, Department of Pathology University of Alabama at Birmingham Birmingham, Alabama Pranav Gandhi, MD, MS Hematopathology Fellow Scripps Clinic La Jolla, California Bertil Glader, MD, PhD Professor, Pediatric Hematology/Oncology Stanford University Palo Alto, California Linda H. Goossen, PhD, MT(ASCP) Professor, Medical Laboratory Science Associate Dean, College of Health Professions Grand Valley State University Grand Valley, Michigan Teresa G. Hippel, BS, MT(ASCP)SH Laboratory Manager Baptist Memorial Hospital Memphis, Tennessee Debra A. Hoppensteadt, BS, MT(ASCP), MS, PhD, DIC Professor of Pathology and Pharmacology Loyola University Chicago Maywood, Illinois Cynthia L. Jackson, PhD Director of Clinical Molecular Biology Lifespan Academic Medical Center Associate Professor of Pathology Warren Alpert Medical School at Brown University Providence, Rhode Island Ameet R. Kini, MD, PhD Director, Division of Hematopathology Medical Director, Hematology & Flow Cytometry Associate Director, Molecular Diagnostics Associate Professor of Pathology, Stritch School of Medicine Loyola University Medical Center Maywood, Illinois Clara Lo, MD Instructor, Pediatric Hematology/Oncology Stanford University Palo Alto, California vip.persianss.ir Contributors ix Sharral Longanbach, MT, SH(ASCP) Senior Technical Application Specialist Siemens Healthcare Diagnostics Deerfield, Illinois Lynn B. Maedel, MS, MLS(ASCP) CM SH CM Executive Director Colorado Association for Continuing Medical Laboratory Education, Inc. (CACMLE) Denver, Colorado Naveen Manchanda, MBBS Associate Professor of Clinical Medicine, Division of Hematology-Oncology Indiana University School of Medicine Indianapolis, Indiana Steven Marionneaux, MS, MT(ASCP) Manager, Clinical Hematology Laboratories Memorial Sloan Kettering Cancer Center New York, New York Adjunct Assistant Professor, Clinical Laboratory Sciences Rutgers, The State University of New Jersey Newark, New Jersey Richard C. Meagher, PhD Section Chief, Cell Therapy Laboratory Department of Laboratory Medicine Memorial Sloan Kettering Cancer Center New York, New York Shashi Mehta, PhD Associate Professor, Clinical Laboratory Sciences School of Health Related Professions Rutgers University, The State University of New Jersey Newark, New Jersey Martha K. Miers, MS, MBA Assistant Professor, Division of Medical Education and Administration Vice Chair, Finance and Administration Department of Pathology, Microbiology, and Immunology Vanderbilt University School of Medicine Nashville, Tennessee JoAnn Molnar, MT(ASCP) Core Laboratory Technical Specialist Loyola University Medical Center Maywood, Illinois Kim A. Przekop, MBA, MLS(ASCP) CM Assistant Professor, Clinical Laboratory Sciences School of Health Related Professions Rutgers, The State University of New Jersey Newark, New Jersey Tim R. Randolph, PhD, MT(ASCP) Chair and Associate Professor, Department of Biomedical Laboratory Science Doisy College of Health Sciences Saint Louis University St. Louis, Missouri Bernadette F. Rodak, MS, CLSpH(NCA), MT(ASCP)SH Professor, Clinical Laboratory Science Program Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis, Indiana Woodlyne Roquiz, DO Hematopathology Fellow Loyola University Medical Center Maywood, Illinois Kathleen M. Sakamoto, MD, PhD Professor and Chief, Division of Hematology/Oncology Department of Pediatrics Stanford University School of Medicine Lucile Packard Children’s Hospital at Stanford Stanford, California Gail H. Vance, MD Sutphin Professor of Cancer Genetics Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis, Indiana Staff Physician Indiana University Health Hospitals Carmel, Indiana Instructor and Student Ancillaries Case Studies, Instructor’s Guide, Test Bank Susan Conforti, EdD, MLS(ASCP)SBB Associate Professor, Medical Laboratory Technology Farmingdale State College Farmingdale, New York PowerPoint Slides Kathleen Doyle, PhD, M(ASCP), MLS(ASCP) CM Medical Laboratory Scientist, Consultant Professor Emeritus, Clinical Laboratory and Nutritional Sciences University of Massachusetts Lowell Lowell, Massachusetts PowerPoint Slides Carolina Vilchez, MS, MLS(ASCP)H Assistant Professor, Clinical Laboratory Sciences School of Health Related Professions Rutgers, The State University of New Jersey Newark, New Jersey vip.persianss.ir x Preface The science of clinical laboratory hematology provides for the analy - sis of normal and pathologic peripheral blood cells, hematopoi - etic (blood-producing) tissue, and the cells in non-vascular body cavities such as cerebrospinal and serous fluids. Laboratory he - matology also includes the analysis of the cells and coagulation proteins essential to clinical hemostasis. Hematology laboratory assay results are critical for the diagnosis, prognosis, and moni - toring treatment for primary and secondary hematologic disor - ders. Similarly, hematology results are used to establish safety in the perioperative period, monitor treatments during surgical procedures, and monitor transfusion needs in trauma patients. Clinical laboratory hematology has been enhanced by pro - found changes as reflected in the numerous updates in the fifth edition of Rodak’s Hematology: Clinical Principles and Applications Automation and digital data management have revolutionized the way blood specimens are transported and stored, how assays are ordered, and how results are validated, reported, and interpreted. Molecular diagnosis has augmented and in many instances replaced long-indispensable laboratory assays. Hematologic disorders have been reclassified on the basis of phenotypic, cytogenetic, and molecular genetic analyses. Diagnoses that once depended on the analysis of cell morphology and cyto - chemical stains now rely on flow cytometry, cytogenetic test - ing, fluorescence in situ hybridization (FISH), end-point and real-time polymerase chain reaction assays, gene sequencing, and microarrays. Traditional chemotherapeutic monitoring of leukemias and lymphomas at the cellular level has shifted to the management of biologic response modifiers and detection of minimal residual disease at the molecular level. Hemostasis has grown to encompass expanded thrombophilia testing, methods that more reliably monitor newly available antiplate - let and anticoagulant drugs, molecular analysis, and a shift from clot-based to functional and chromogenic assays. Rodak’s Hematology: Clinical Principles and Applications sys - tematically presents basic to advanced concepts to provide a solid foundation of normal and pathologic states upon which readers can build their skills in interpreting and correlating laboratory findings in anemias, leukocyte disorders, and hem - orrhagic and thrombotic conditions. It provides key features for accurate identification of normal and pathologic cells in blood, bone marrow, and body fluids. The focus, level, and detail of hematology and hemostasis testing, along with the related clinical applications, interpretation, and testing algo - rithms, make this text a valuable resource for all healthcare professionals managing these disorders. ORGANIZATION Rodak’s Hematology: Clinical Principles and Applications fifth edition is reorganized into 7 parts and 45 chapters for enhanced pedagogy. Chapter highlights and new content are described as follows: Preface Part I: Introduction to Hematology Chapters 1 to 5 preview the science of clinical laboratory hema - tology and include laboratory safety, blood specimen collection, microscopy, and quality assurance. The quality assurance chap - ter was significantly updated to include enhanced sections on statistical significance; assay validation with applications of the Student’s t test, ANOVA, linear regression, and Bland-Altman difference plots; and assessment of diagnostic efficacy. Part II: Blood Cell Production, Structure, and Function Chapters 6 and 7 use photomicrographs and figures to describe general cellular structure and function and the morphologic and molecular details of hematopoiesis. Chapters 8, 12, and 13 dis - cuss erythropoiesis, leukopoiesis, and megakaryopoiesis using numerous photomicrographs demonstrating ultrastructure and microscopic morphology. Chapters 9 and 10 examine mature red blood cell metabolism, hemoglobin structure and function, and red blood cell senescence and destruction. Iron kinetics and labo - ratory assessment in Chapter 11 was substantially updated with new figures and updated coverage of systemic and cellular regula - tion of iron. Chapter 13 includes detailed descriptions of platelet adhesion, aggregation, and activation with updated figures. Part III: Laboratory Evaluation of Blood Cells Chapter 14 describes manual procedures such as microscopy- based cell counts, hemoglobin and hematocrit determinations, and point-of-care technology. Chapter 15 has been substan - tially updated to include descriptions and figures of the latest automated hematology analyzers. Chapter 16 describes pe - ripheral blood film examination and the differential count correlation to the complete blood count. New figures correlate red blood cell and platelet histograms to their morphology. Chapter 17 follows up with bone marrow aspirate and biopsy collection, preparation, examination, and reporting. Chapter 18 describes methods for analyzing normal and pathologic cells of cerebrospinal fluid, joint fluid, transudates, and exu - dates, illustrated with many excellent photomicrographs. Part IV: Erythrocyte Disorders Chapter 19 provides an overview of anemia and describes cost- effective approaches that integrate patient history, physical ex - amination, and symptoms with the hemoglobin, red blood cell indices, reticulocyte count, and abnormal red blood cell mor - phology. Chapters 20 to 22 describe disorders of iron and DNA metabolism and bone marrow failure. New algorithms help the reader to distinguish types of microcytic and macrocytic ane - mias. Chapters 23 to 26 discuss hemolytic anemias due to in - trinsic or extrinsic defects. Chapter 23 is fully updated with new figures that detail extravascular and intravascular hemolysis and hemoglobin catabolism. Chapters 27 and 28 provide updates in x vip.persianss.ir Preface xi technicians, and the faculty of undergraduate and graduate edu - cational programs in the clinical laboratory sciences. This text is also a helpful study guide for pathology and hematology- oncology residents and fellows and a valuable shelf reference for hematologists, pathologists, and hematology and hemosta - sis laboratory managers. TEXTBOOK FEATURES Elaine M. Keohane , PhD, MLS, Professor, Rutgers University, School of Health Related Professions, Department of Clinical Laboratory Sciences, co-editor in the fourth edition, and lead editor in the fifth edition, is joined by Larry J. Smith , PhD, Coagulation and Satellite Laboratory Director, Memorial Sloan Kettering Cancer Center, Adjunct Professor at Rutgers Univer - sity, School of Health Related Professions and York College, CUNY, Department of Health Professions, and Jeanine M. Walenga , PhD, MT(ASCP), Professor, Loyola University Chi - cago, Stritch School of Medicine, Clinical Coagulation Labora - tories Director, Loyola University Health System. The outstanding value and quality of Rodak’s Hematology: Clinical Principles and Applications reflect the educational and clinical expertise of its current and previous authors and editors. The text is enhanced by nearly 700 full-color digital photomicro - graphs, figures, and line art. Detailed text boxes and tables clearly summarize important information. Reference intervals are pro - vided on the inside front and back covers for quick lookup. Each chapter contains the following pedagogical features: • Learning objectives at all taxonomy levels in the cogni - tive domain. • One or two case studies with open-ended discussion questions at the beginning of the chapter that stimulate interest and provide opportunities for application of chapter content in real-life scenarios. • A bulleted summary at the end of each chapter that pro - vides a comprehensive review of essential material. • Review questions at the end of each chapter that corre - late to chapter objectives and are in the multiple-choice format used by certification examinations. • Answers to case studies and review questions that are provided in the Appendix. The Evolve website has multiple features for the instructor: • An ExamView test bank contains multiple-choice ques - tions with rationales and cognitive levels. • Instructor’s manuals for every chapter contain key terms, objectives, outlines, and study questions. • Learning Objectives with taxonomy levels are provided to supplement lesson plans. • Case studies have been updated and feature discussion questions and photomicrographs when applicable. • PowerPoint presentations for every chapter can be used “as is” or as a template to prepare lectures. • The Image Collection provides electronic files of all the chapter figures that can be downloaded into PowerPoint presentations. For the student, a Glossary is available as a quick reference to look up unfamiliar terms electronically. pathophysiology, diagnosis, and treatment of hemoglobinopa - thies (such as sickle cell disease) and the thalassemias. Part V: Leukocyte Disorders Chapter 29 is significantly updated with many excellent photo - micrographs and summary boxes of nonmalignant systemic disorders manifested by the abnormal distribution or morphol - ogy of leukocytes. These include bacterial and viral infections, various systemic disorders, and benign lymphoproliferative dis - orders. Chapter 30 provides details on traditional cytogenetic procedures for detection of quantitative and qualitative chromo - some abnormalities and more sensitive methods such as FISH and genomic hybridization arrays. Chapter 31 covers molecular diagnostics and was fully updated with new and enhanced fig - ures on basic molecular biology, end-point and real-time poly - merase chain reaction, microarrays, and DNA sequencing, in - cluding next generation sequencing. Chapter 32 describes flow cytometry and its diagnostic applications. It includes numerous scatterplots of normal and leukemic conditions. Chapters 33 to 36, with significant updating, provide the latest classifications and pathophysiologic models for myeloproliferative neoplasms, myelodysplastic syndromes, acute lymphoblastic and myeloid leukemias, chronic lymphocytic leukemia, and solid tumor lym - phoid neoplasms, such as lymphoma and myeloma, with nu - merous full-color photomicrographs and illustrations. Part VI: Hemostasis and Thrombosis Chapter 37 provides the plasma-based and cell-based coagula - tion models and the interactions between primary and second - ary hemostasis and fibrinolysis with updated illustrations. Chapter 38 details hemorrhagic disorders, including the man - agement of the acute coagulopathy of trauma and shock. Chapter 39 updates the currently recognized risk factors of thrombosis and describes laboratory tests that identify venous and arterial thrombotic diseases, particularly for lupus antico - agulant and heparin-induced thrombocytopenia (HIT) testing. Chapters 40 and 41 detail the quantitative and qualitative platelet disorders using additional tables and figures, and Chapter 42 details laboratory assays of platelets and the coagu - lation mechanisms with helpful new figures and diagrams. Chapter 43 covers the mechanisms and monitoring methods of the traditional warfarin and heparin-derived antithrombotic drugs, as well as all thrombin and factor Xa inhibitor drugs. It also includes methods for monitoring the different classes of antiplatelet drugs, including aspirin. Chapter 44 reviews the latest coagulation analyzers and point of care instrumentation. Part VII: Hematology and Hemostasis in Selected Populations Chapter 45 provides valuable information on the hematology and hemostasis laboratory findings in the pediatric and geriatric populations correlated with information from previous chapters. READERS Rodak’s Hematology: Clinical Principles and Applications is de - signed for medical laboratory scientists, medical laboratory vip.persianss.ir xii Preface The editors express their immense gratitude to Bernadette F. (Bunny) Rodak, who laid the foundation for this textbook with her expert writing, editing, detailed figures, and especially her contribution of over 200 outstanding digital photomicrographs over the past 2 decades. Now in its fifth edition, she has authored three chapters, provided invaluable contributions and assistance with additional photomicrographs and figures, and provided the opportunity for us to continue her work on this outstanding textbook. We sincerely thank George A. Fritsma for his significant contribution to this text as a previous coeditor and author, for sharing his immense expertise in hemostasis, for updating and authoring ten chapters in the fifth edition, and for his constant support and encouragement. We thank Kathryn Doig for her contributions as coeditor for the third edition; author in previous editions; and for her tenaciousness, creativ - ity, and care in updating the five chapters authored in the fifth edition. The editors also thank the many authors who have made and continue to make significant contributions to this work. All of these outstanding professionals have generously Acknowledgments shared their time and expertise to make Rodak’s Hematology: Clinical Principles and Applications into a worldwide educational resource and premier reference textbook for medical laboratory scientists and technicians, as well as pathology and hematology practitioners, residents, and fellows. We also express our appreciation to Elsevier, especially Ellen Wurm-Cutter, Laurie Gower, Kellie White, Sara Alsup, Megan Knight, and Rebecca Corradetti, whose professional support and reminders kept the project on track, and to Debbie Prato for her editorial assistance. Finally, and with the utmost gratitude, we acknowledge our families, friends, and professional colleagues who have sup - ported and encouraged us through this project. Elaine M. Keohane, PhD, MLS Larry J. Smith, PhD, SH(ASCP), HCLD/CC(ABB) Jeanine M. Walenga, PhD, MT(ASCP) xii vip.persianss.ir Contributors xiii Contents PART I Introduction to Hematology CHAPTER 1 An Overview of Clinical Laboratory Hematology, 1 George A. Fritsma CHAPTER 2 Safety in the Hematology Laboratory, 8 Sheila A. Finch CHAPTER 3 Blood Specimen Collection, 19 Elaine M. Keohane CHAPTER 4 Care and Use of the Microscope, 34 Bernadette F. Rodak CHAPTER 5 Quality Assurance in Hematology and Hemostasis Testing, 42 George A. Fritsma PART II Blood Cell Production, Structure, and Function CHAPTER 6 Cellular Structure and Function, 65 Elaine M. Keohane CHAPTER 7 Hematopoiesis, 76 Richard C. Meagher CHAPTER 8 Erythrocyte Production and Destruction, 95 Kathryn Doig CHAPTER 9 Erythrocyte Metabolism and Membrane Structure and Function, 112 George A. Fritsma CHAPTER 10 Hemoglobin Metabolism, 124 Elaine M. Keohane CHAPTER 11 Iron Kinetics and Laboratory Assessment, 137 Kathryn Doig CHAPTER 12 Leukocyte Development, Kinetics, and Functions, 149 Woodlyne Roquiz, Sameer Al Diffalha, and Ameet R. Kini CHAPTER 13 Platelet Production, Structure, and Function, 167 George A. Fritsma PART III Laboratory Evaluation of Blood Cells CHAPTER 14 Manual, Semiautomated, and Point-of-Care Testing in Hematology, 187 Karen S. Clark and Teresa G. Hippel CHAPTER 15 Automated Blood Cell Analysis, 208 Sharral Longanbach and Martha K. Miers CHAPTER 16 Examination of the Peripheral Blood Film and Correlation with the Complete Blood Count, 235 Lynn B. Maedel and Kathryn Doig CHAPTER 17 Bone Marrow Examination, 253 George A. Fritsma CHAPTER 18 Body Fluid Analysis in the Hematology Laboratory, 269 Bernadette F. Rodak PART IV Erythrocyte Disorders CHAPTER 19 Anemias: Red Blood Cell Morphology and Approach to Diagnosis, 284 Naveen Manchanda CHAPTER 20 Disorders of Iron Kinetics and Heme Metabolism, 297 Kathryn Doig CHAPTER 21 Anemias Caused by Defects of DNA Metabolism, 314 Linda H. Goossen CHAPTER 22 Bone Marrow Failure, 331 Clara Lo, Bertil Glader, and Kathleen M. Sakamoto CHAPTER 23 Introduction to Increased Destruction of Erythrocytes, 348 Kathryn Doig CHAPTER 24 Intrinsic Defects Leading to Increased Erythrocyte Destruction, 367 Elaine M. Keohane xiii vip.persianss.ir xiv Contents PART VI Hemostasis and Thrombosis CHAPTER 37 Normal Hemostasis and Coagulation, 642 Margaret G. Fritsma and George A. Fritsma CHAPTER 38 Hemorrhagic Disorders and Laboratory Assessment, 667 George A. Fritsma CHAPTER 39 Thrombotic Disorders and Laboratory Assessment, 689 George A. Fritsma CHAPTER 40 Thrombocytopenia and Thrombocytosis, 713 Larry D. Brace CHAPTER 41 Qualitative Disorders of Platelets and Vasculature, 739 Larry D. Brace CHAPTER 42 Laboratory Evaluation of Hemostasis, 760 George A. Fritsma CHAPTER 43 Antithrombotic Therapies and Their Laboratory Assessment, 790 George A. Fritsma CHAPTER 44 Hemostasis and Coagulation Instrumentation, 810 Debra A. Hoppensteadt and JoAnn Molnar PART VII Hematology and Hemostasis in Selected Populations CHAPTER 45 Pediatric and Geriatric Hematology and Hemostasis, 829 Linda H. Goossen APPENDIX Answers, 847 Glossary, 857 Index, 877 CHAPTER 25 Extrinsic Defects Leading to Increased Erythrocyte Destruction—Nonimmune Causes, 394 Elaine M. Keohane CHAPTER 26 Extrinsic Defects Leading to Increased Erythrocyte Destruction—Immune Causes, 411 Kim A. Przekop CHAPTER 27 Hemoglobinopathies (Structural Defects in Hemoglobin), 426 Tim R. Randolph CHAPTER 28 Thalassemias, 454 Elaine M. Keohane PART V Leukocyte Disorders CHAPTER 29 Nonmalignant Leukocyte Disorders, 475 Steven Marionneaux CHAPTER 30 Cytogenetics, 498 Gail H. Vance CHAPTER 31 Molecular Diagnostics in Hematopathology, 513 Cynthia L. Jackson and Shashi Mehta CHAPTER 32 Flow Cytometric Analysis in Hematologic Disorders, 543 Magdalena Czader CHAPTER 33 Myeloproliferative Neoplasms, 561 Tim R. Randolph CHAPTER 34 Myelodysplastic Syndromes, 591 Bernadette F. Rodak CHAPTER 35 Acute Leukemias, 604 Woodlyne Roquiz, Pranav Gandhi, and Ameet R. Kini CHAPTER 36 Mature Lymphoid Neoplasms, 619 Magdalena Czader vip.persianss.ir 1 PART I Introduction to Hematology OUTLINE History Red Blood Cells Hemoglobin, Hematocrit, and Red Blood Cell Indices Reticulocytes White Blood Cells Platelets Complete Blood Count Blood Film Examination Endothelial Cells Coagulation Advanced Hematology Procedures Additional Hematology Procedures Hematology Quality Assurance and Quality Control 1 An Overview of Clinical Laboratory Hematology George A. Fritsma T he average human possesses 5 liters of blood. Blood transports oxygen from lungs to tissues; clears tissues of carbon dioxide; transports glucose, proteins, and fats; and moves wastes to the liver and kidneys. The liquid portion is plasma, which, among many components, provides coagulation enzymes that protect vessels from trauma and maintain the circulation. Plasma transports and nourishes blood cells. There are three categories of blood cells: red blood cells (RBCs), or erythrocytes; white blood cells (WBCs), or leukocytes; and platelets (PLTs), or thrombocytes 1 Hematology is the study of these blood cells. By expertly staining, counting, analyzing, and recording the appearance, phenotype, and genotype of all three types of cells, the medical laboratory professional (technician or scientist) is able to predict, detect, and diagnose blood diseases and many systemic dis - eases that affect blood cells. Physicians rely on hematology laboratory test results to select and monitor therapy for these disorders; consequently, a complete blood count (CBC) is ordered on nearly everyone who visits a physician or is admitted to a hospital. HISTORY The first scientists such as Athanasius Kircher in 1657 described “worms” in the blood, and Anton van Leeuwenhoek in 1674 gave an account of RBCs, 2 but it was not until the late 1800s that Giulio Bizzozero described platelets as “petites plaques.” 3 The development of Wright stain by James Homer Wright in 1902 opened a new world of visual blood film examination through the micro - scope. Although automated instruments now differentiate and enumerate blood cells, Wright’s Romanowsky-type stain (polychromatic, a mixture of acidic and basic dyes), and refinements thereof, remains the foundation of blood cell identification. 4 In the present-day hematology laboratory, RBC, WBC, and platelet appearance is analyzed through automation or visually using 500 3 to 1000 3 light microscopy examination of cells fixed to a glass microscope slide and stained with Wright or Wright-Giemsa stain (Chapters 15 and 16). The scientific term for cell appearance is morphology, which encompasses cell color, size, shape, cytoplasmic inclu - sions, and nuclear condensation. RED BLOOD CELLS RBCs are anucleate, biconcave, discoid cells filled with a reddish pro