Rodak hematology 4th ed free download

Unless otherwise noted, data for reference range tables were compiled from multiple sources and may vary slightly from ranges listed within chapters.
Each laboratory must establish its particular ranges based on its instrumentation, methodology, and demographics of the population it serves.

Hematology Reference Ranges (Adult)

Assay Adult Male Adult Female Common Units SI Units
RBC 4.60-6.00 4.00-5.40 106/L 1012/L
HGB (Hb) 14.0-18.0 12.0-15.0 g/dL (g/L)
(140-180) (120-150)
HCT 40-54 35-49 % (L/L)
(0.40-0.54) (0.35-0.49)
MCV 80-100 80-100 fL fL
MCH 26-32 26-32 pg pg
MCHC 32-36 32-36 % g/dL
RDW 11.5-14.5 11.5-14.5 % %
Retics (automated) 25-75 25-75 103/L 109/L
Visual retics* 0.5-1.5 0.5-1.5 %
NRBCs 0 0 /100WBC /100WBC
WBCs 4.5-11.5 4.5-11.5 103/L 109/L
% ABS % ABS 103/L 109/L
SEGs (PMNs) 50-70 2.3-8.1 50-70 2.3-8.1 103/L 109/L
BANDs 0-5 0-0.6 0-5 0-0.6 103/L 109/L
ANC 2.3-8.1 2.3-8.1 103/L 109/L
LYMPHs 18-42 0.8-4.8 18-42 0.8-4.8 103/L 109/L
MONOs 2-11 0.45-1.3 2-11 0.45-1.3 103/L 109/L
EOs 1-3 0-0.4 1-3 0-0.4 103/L 109/L
BASOs 0-2 0-0.1 0-2 0-0.1 103/L 109/L
PLTs 150-450 150-450 103/L 109/L
MPV 6.8-10.2 6.8-10.2 fL fL
Erythrocyte mass <36mL/kg <32mL/kg
Erythrocyte sedimentation rate, 0-50 years: 0-15mm 0-50 years: 0-20mm
Westergren 1 hour >50 years: 0-20mm >50 years: 0-30mm

*Reticulocyte counts performed by manual methods.

HGB, Hemoglobin; HCT, hematocrit; MCV, mean cell volume; MCH, mean cell hemoglobin; MCHC, mean cell hemoglobin concentration; RDW, red blood cell distribution width;
MPV, mean platelet volume; PLTs, platelets; PMNs, polymorphonuclear neutrophils; Segs, segmented neutrophils; Lymphs, lymphocytes; Monos, monocytes; Eos, eosinophils;
Basos, basophils; ANC, absolute neutrophil count, includes segs and bands; Retic, reticulocyte.

Tests Commonly Used to Assess Anemia (same for male and female, except noted)
Test Reference Interval
Serum Iron 50-160g/dL
Total iron-binding capacity 250-400g/dL
Percent transferrin saturation 20-55
Serum ferritin, male 15-400g/mL
Serum ferritin, female 10-106g/mL
Vitamin B12 200-850pg/mL
Serum folate 2.0-10.0g/mL
RBC folate >120g/mL
HGB A (electrophoresis) 95-100%
HGB A2 (electrophoresis) 0-3.5%
HGB F, Adult 0-2.0%
HGB F, Newborn 65-90%
Haptoglobin 31-209mg/dL
Free serum hemoglobin 0-10mg/dL

RBC, Red blood cell; HGB, hemoglobin.

Hematology Reference Ranges (Pediatric)
Common
Assay 0-1d 2-4d 5-7d 8-14d 15-30d 1-2mo 3-5mo 6-11mo 1-3y 4-7y 8-13y Units SI Units
RBC 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 4.00-5.40 106/L 1012/L
HGB (Hb) 16.5-21.5 16.4-20.8 15.2-20.4 15.0-19.6 12.2-18.0 10.6-16.4 10.4-16.0 10.4-15.6 9.6-15.6 10.2-15.2 12.0-15.0 g/dL (g/L)
(165-215) (164-208) (152-204) (150-196) (122-180) (106-164) (104-160) (104-156) (96-156) (102-152) (120-150)
HCT 48-68 48-68 50-64 46-62 38-53 32-50 35-51 35-51 38-48 34-48 35-49 % L/L
MCV 95-125 98-118 100-120 95-115 93-113 83-107 78-102 76-92 78-94 80-94 80-94 fL fL
MCH 30-42 30-42 30-42 30-42 28-40 27-37 25-35 23-31 23-31 23-31 26-32 pg pg
MCHC 30-34 30-34 30-34 30-34 30-34 31-36 32-36 32-36 32-36 32-36 32-36 % g/dL
RDW * * * * * * * 11.5-14.5 11.5-14.5 11.5-14.5 11.5-14.5 % %
RETICs 1.5-5.8 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 % %
NRBCs 2-24 5-9 0-1 0 0 0 0 0 0 0 0 /100WBC /100WBC
WBC 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 4.5-13.5 103/L 109/L
SEGs/PMNs 37-67 30-60 27-51 22-46 20-40 20-40 18-38 20-40 22-46 29-65 23-53 % %
BANDs 3-11 3-9 1-9 0-5 0-5 0-5 0-5 0-5 0-5 0-5 0-5 % %
LYMPHs 18-38 16-46 24-54 30-62 41-61 42-72 45-75 48-78 37-73 29-65 23-53 % %
MONOs 3-14 4-17 2-15 3-14 2-11 2-11 2-11 2-11 2-11 2-11 2-11 % %
EOs 1-4 1-5 2-6 1-5 1-5 1-4 1-4 1-4 1-4 1-4 1-4 % %
BASOs 0-2 0-2 0-2 0-2 0-2 0-2 0-2 0-2 0-2 0-2 0-2 % %
ANC 3.7-30 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 1.6-9.5 103/L 109/L
PLTs 150-450 103/L 109/L

*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.
From Riley Hospital for Children, Indiana University Health, Indianapolis, IN.
HGB, Hemoglobin; PMNs, polymorphonuclear neutrophils; HCT, hematocrit; MCV, mean cell volume; MCH, mean cell hemoglobin; MCHC, mean cell hemoglobin concentration;
RDW, red blood cell distribution width; Lymphs, lymphocytes; Monos, monocytes; Eos, eosinophils; ANC, absolute neutrophil count, includes segs and band; Segs, segmented
neutrophils; Retic, reticulocyte count; PLTs, platelets; Basos, basophils; NRBC, nucleated red blood cells.

Bone Marrow Aspirate

WBC Differential Range (%) Erythrocyte Series Range (%)
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 Megakaryoctyes 2-10/lpf
Plasma cells 0-1
Monocytes 0-1
Histiocytes (macrophages) 0-1

N, Neutrophilic; NB, normoblast; M:E, myeloid:erythroid; lpf, low power field.

 REGISTER TODAY!

To access your Student Resources, visit:

http://evolve.elsevier.com/Rodak/

Register today and gain access to:

Glossary
Provides definitions for essential hematology terms.
Weblinks
Links to places of interest on the web specifically for
hematology.
BE R N A D E T T E F . R O D A K , MS, MLS
Professor
Clinical Laboratory Science Program
Department of Pathology and Laboratory Medicine
Indiana University School of Medicine
Indianapolis, Indiana

GE O R G E A . F R I T S M A , MS, MLS
Manager
The Fritsma Factor, Your Interactive Hemostasis Resource
Birmingham, Alabama

EL A I N E M . K E O H A N E , PhD, MLS
Professor
Department of Clinical Laboratory Sciences
University of Medicine and Dentistry of New Jersey
School of Health Related Professions
Newark, New Jersey
3251 Riverport Lane
St. Louis, Missouri 63043

HEMATOLOGY: CLINICAL PRINCIPLES AND APPLICATIONS ISBN: 978-1-4377-0692-5

Copyright 2012, 2007, 2002, 1995 by Saunders, an imprint of Elsevier Inc.

Chapter 47: Coagulation Instrumentation by David L. McGlasson is Public Domain.

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by
any means, electronic or mechanical, including photocopy, recording, or any information storage and
retrieval system, without permission in writing from the publisher.

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 Publishers 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.

ISBN 978-1-4377-0692-5

Publishing Director: Andrew Allen

Managing Editor: Ellen Wurm-Cutter
Publishing Services Manager: Catherine Jackson
Senior Project Manager: David Stein
Senior Designer: Amy Buxton

Working together to grow

libraries in developing countries
Printed in China www.elsevier.com | www.bookaid.org | www.sabre.org

Last digit is the print number: 9 8 7 6 5 4 3 2

 To my husband, Bob, for his continued patience,
understanding, encouragement, and love.
And to Annie, who missed her walk times
and is glad to have them back.
BFR

To my wife, Margaret, and children, Greg and Teri,

for their love, support, and loyalty.
GAF

To my students for being great teachers,

and to Camryn, Riley, Harper, Jackie, Alana, and Kenny
for reminding me about the important things in life.
EMK
This page intentionally left blank
 Reviewers
Shamina Davis, MS, MT(ASCP) Amy Kapanka, MS, MT(ASCP)SC
Faculty, Bachelors of Applied Technology MLT Program Director and Professor
College of Applied Technologies and General Studies Hawkeye Community College
Office of Applied Technology Waterloo, Iowa
University of Texas at Brownsville
Brownsville, Texas E. Anne Stiene-Martin, PhD, MT(ASCP)
Professor Emeritus
David Hoblit, MD Department of Clinical and Reproductive Sciences
Faculty, Department of Pathology University of Kentucky
University of North Texas Health Science Center Lexington, Kentucky
Instructor, Department of Clinical Laboratory Science
Tarleton State University
Fort Worth, Texas

vii
 Contributors

Larry D. Brace, PhD, MT(ASCP)SH Magdalena Czader, MD, PhD

Emeritus Professor of Pathology Associate Professor and Director
University of Illinois at Chicago Division of Hematopathology
Chicago, Illinois Department of Pathology and Laboratory Medicine
Scientific Director of Laboratories Director, Clinical Flow Cytometry Laboratory
Edward Hospital Indiana University School of Medicine
Naperville, Illinois Indianapolis, Indiana
Thrombocytopenia and Thrombocytosis Flow Cytometric Analysis in Hematologic Disorders
Qualitative Disorders of Platelets and Vasculature Mature Lymphoid Neoplasms

Deanne H. Chapman, BS, MT(ASCP)SH Kathryn Doig, PhD, MT(ASCP)

Technical Sales Manager Professor and Associate Dean
Bayer HealthCare LLC, Diagnostics Division Biomedical Laboratory Diagnostics
Tarrytown, New York College of Natural Science
Automated Cell-Counting Instrumentation Michigan State University
East Lansing, Michigan
Karen S. Clark, BS, MT(ASCP)SH Erythrocyte Production and Destruction
Point of Care Manager Energy Metabolism and Membrane Physiology of the Erythrocyte
Baptist Memorial Hospital Examination of the Peripheral Blood Film and Correlation with the Complete
Memphis, Tennessee Blood Count
Routine and Point-of-Care Testing in Hematology: Manual and Disorders of Iron and Heme Metabolism
Semiautomated Methods Introduction to Increased Destruction of Erythrocytes

Mary Coleman, MS, MLS(ASCP)CM, SH(ASCP)CM, Peter D. Emanuel, MD

CG(ASCP)CM Director, Winthrop P. Rockefeller Cancer Institute
Assistant Professor Professor of Medicine
Department of Pathology Kent Westbrook, MD Endowed Chair
University of North Dakota Clinical Laboratory University of Arkansas for Medical Sciences
Science Program Little Rock, Arkansas
Grand Forks, North Dakota Introduction to Leukocyte Neoplasms
Hemoglobin Metabolism
Iron Metabolism Sheila A. Finch, CHSP, CHMM, MS, BS, MT(ASCP)
System Director, Environment of Care/ISO Administrator
Leilani Collins, MS, MT(ASCP)SH Detroit Medical Center
Associate Professor Detroit, Michigan
Medical Technology Program Safety in the Hematology Laboratory
College of Allied Health Science
University of Tennessee Health Science Center
Memphis, Tennessee
Body Fluids in the Hematology Laboratory

viii
 Contributors ix

George A. Fritsma, MS, MLS Mark E. Lasbury, MS, PhD

Manager Assistant Scientist
The Fritsma Factor, Your Interactive Hemostasis Resource Department of Pathology and Laboratory Medicine
Birmingham, Alabama Indiana University School of Medicine
An Overview of Clinical Laboratory Hematology Indianapolis, Indiana
Quality Assurance in Hematology and Hemostasis Testing Molecular Diagnostics in the Clinical Laboratory
Energy Metabolism and Membrane Physiology of the Erythrocyte
Platelet Production, Structure, and Function Susan J. Leclair, PhD, MLS
Bone Marrow Examination Chancellor Professor
Normal Hemostasis and Coagulation Department of Medical Laboratory Science
Hemorrhagic Coagulation Disorders University of Massachusetts Dartmouth
Thrombosis Risk Testing Dartmouth, Massachusetts
Laboratory Evaluation of Hemostasis Acute Leukemias
Monitoring Antithrombotic Therapies
Sharral Longanbach, SH(ASCP)
Margaret G. Fritsma, MA, MT(ASCP)SBB Senior Technical Application Specialist
Associate Professor, Retired Siemens Healthcare Diagnostics
School of Health Professions Deerfield, Illinois
Division of Laboratory Medicine, Department of Pathology Automated Cell-Counting Instrumentation
University of Alabama at Birmingham
Birmingham, Alabama Lynn B. Maedel, MS, MLS(ASCP)SH
Normal Hemostasis and Coagulation Executive Director
Glossary Colorado Association for Continuing Medical Laboratory
Education, Inc. (CACMLE)
Linda H. Goossen, PhD, MT(ASCP) Denver, Colorado
Professor Adjunct Faculty
Clinical Laboratory Science Michigan State University
College of Health Professions East Lansing, Michigan
Grand Valley State University Examination of the Peripheral Blood Film and Correlation with the Complete
Grand Rapids, Michigan Blood Count
Anemias Caused by Defects of DNA Metabolism
Pediatric and Geriatric Hematology David L. McGlasson, MS, MLS(ASCP)CM
Clinical Research Scientist
Teresa G. Hippel, BS, MT(ASCP)SH Clinical Research Division
Laboratory Manager Wilford Hall Medical Center
Baptist Memorial Hospital United States Air Force
Memphis, Tennessee Lackland Air Force Base, Texas
Routine and Point-of-Care Testing in Hematology: Manual and Coagulation Instrumentation
Semiautomated Methods
Rakesh P. Mehta, MD
Elaine M. Keohane, PhD, MLS Assistant Professor of Clinical Medicine
Professor Indiana University School of Medicine
Department of Clinical Laboratory Sciences Indianapolis, Indiana
University of Medicine and Dentistry of New Jersey Anemias: Red Blood Cell Morphology and Approach to Diagnosis
School of Health Related Professions Thalassemias
Newark, New Jersey
Bone Marrow Failure Martha K. Miers, MS, MBA
Intrinsic Defects Leading to Increased Erythrocyte Destruction Assistant Professor
Extrinsic Defects Leading to Increased Erythrocyte Destruction Division of Medical Education and Administration
Nonimmune Causes Vice Chair, Finance and Administration
Extrinsic Defects Leading to Increased Erythrocyte Destruction Department of Pathology
Immune Causes Vanderbilt University School of Medicine
Thalassemias Nashville, Tennessee
Automated Cell-Counting Instrumentation
x Contributors

Carole A. Mullins, MPA, CLDir(NCA), BS, MT(ASCP) Larry Smith, PhD, SH(ASCP)
Adjunct Faculty Assistant Attending Scientist, Director
Nursing and Human Services Coagulation and Hemostasis Laboratories
Southwestern Michigan College Department of Clinical Laboratories
Dowagiac, Michigan Memorial Sloan-Kettering Cancer Center
Specimen Collection New York, New York
Hematopoiesis
Keila B. Poulsen, BS, MLS(ASCP)CM H, SH
Adjunct Faculty Anne Stiene-Martin, PhD
Brigham Young University Professor Emeritus
Provo, Utah Clinical Laboratory Science Program
Hematology/Histology Supervisor Department of Clinical Science
Eastern Idaho Regional Medical Center College of Health Sciences
Idaho Falls, Idaho University of Kentucky
Cellular Structure and Function Lexington, Kentucky
Leukocyte Development, Kinetics, and Functions
Tim R. Randolph, PhD, MLS Nonmalignant Leukocyte Disorders
Associate Professor
Department of Clinical Laboratory Science Gail H. Vance, MD
Doisy College of Health Sciences Professor
Saint Louis University Indiana University School of Medicine
Saint Louis, Missouri Department of Medical and Molecular Genetics
Hemoglobinopathies (Structural Defects in Hemoglobin) Indiana UniversityPurdue University at Indianapolis
Myeloproliferative Neoplasms Clarian Health Hospitals
Staff Physician
Bernadette F. Rodak, MS, MLS Indianapolis, Carmel and Lafayette, Indiana
Professor Cytogenetics
Clinical Laboratory Science Program
Department of Pathology and Laboratory Medicine
Indiana University School of Medicine
Indianapolis, Indiana
Care and Use of the Microscope
Cytochemistry
Myelodysplastic Syndromes
Acute Leukemias
 Preface

The science of clinical laboratory hematology provides for the reorganized for enhanced clarity. The discussion of white blood
analysis of normal and pathologic peripheral blood cells, cell disorders includes details of the updated World Health
hematopoietic (blood-producing) tissue, and the cells in Organization leukemia and lymphoma classifications that
cerebrospinal and serous fluid. Laboratory hematology also apply molecular techniques to detect BCR/ABL, JAK2, gene
analyzes the cells and plasma enzymes essential to clinical rearrangement, and newly described genetic markers. These
hemostasis. Although the hematology laboratory is closely chapters have been rewritten to reflect the WHO classification
aligned with clinical hematology, an internal medicine subspe- and to blend time-honored morphologic techniques with flow
cialty of oncology, it provides fundamental information for all cytometry and molecular analyses. The hemostasis chapters
patients requiring the services of the specialties of medicine now include references to emerging platelet analysis techno
and surgery. Hematology laboratory assay results help predict, logies and methods for monitoring the antiplatelet drugs
diagnose, establish the prognosis for, and monitor the treat- eptifibitide, abciximab, integrilin, clopidogrel, prasugrel, and
ment for a variety of medical disorders. Likewise hematology aspirin. The authors have updated anticoagulant monitoring
results are used to establish the need for surgery, monitor the descriptions to include chromogenic substrate analyses and
effects of surgery, and monitor treatments that support surgical new means for monitoring direct thrombin inhibitors and the
procedures. oral anticoagulants rivaroxaban, dabigatran, and apixiban, cur-
Clinical laboratory hematology has been enhanced by pro- rently in clinical trials. Sections on automated coagulometers
found changes, as reflected in the numerous updates in this, and point-of-care coagulation testing are rewritten for clarity
the fourth edition of Hematology: Clinical Principles and Applica- and timeliness.
tions. Automation and digital data management have revolu-
tionized the way blood specimens are transported and stored,
ORGANIZATION
the way laboratory assays are ordered, the way laboratory assay
results are validated and reported, and the clinical science of Hematology: Clinical Principles and Applications is organized into
laboratory result interpretation. 8 parts, 47 chapters, a detailed appendix, and a fully rewritten
Molecular diagnosis has augmented and in many instances glossary.
replaced long-indispensable laboratory assays. Hematological
disorders have been reclassified on the basis of phenotypic, Part I: Introduction to Hematology
cytogenetic, and point mutation analyses. Diagnoses that once Chapters 1 to 5 preview the science of clinical laboratory hema-
depended on the analysis of cell morphology and cytochemical tology and discuss current approaches to medical laboratory
stains now rely on flow cytometry, cytogenetic testing, fluo scientist and patient safety, peripheral blood specimen collec-
rescence in situ hybridization, end-point and real-time poly- tion, care and use of the light microscope, and hematology and
merase chain reaction assays, gene sequencing, and microarrays. hemostasis quality assurance. Updates to the quality assurance
Therapeutic regimen monitoring has shifted to the manage- chapter include discussions of new assay validation, accuracy
ment of biologic response modifiers in place of traditional and precision exercises, moving averages, lot-to-lot validations,
chemotherapy and minimal residual disease characterization clinical efficacy analyses, and receiver-operating characteristic
at the molecular and not the cellular level. Hemostasis has analyses.
grown to encompass thrombophilia testing, methods that reli-
ably monitor newly available antiplatelet and anticoagulant Part II: Hematopoiesis
drugs, molecular analysis, and a shift from clot-based to func- Chapters 6 to 13, richly illustrated with color-balanced photo-
tional and chromogenic assays. micrographs, describe the components of a hematologic cell
Some specific advances that appear in this fourth edition of and the biological and genetic details of erythropoiesis (red
Hematology: Clinical Principles and Applications include updated blood cell production), leukopoiesis (white blood cell produc-
stem cell differentiation models based on increased under- tion), and megakaryopoiesis (platelet production). Chapters 9
standing of cell signaling mechanisms and anemia classifica- to 11 examine mature red blood cell metabolism; iron metabo-
tions that incorporate updated cell membrane structure and lism; the production, structure, and function of hemoglobin;
receptors, cytochemical growth factors, and single nucleotide and red blood cell senescence and destruction. Chapter 12
polymorphism analyses. The chapters on hemolytic anemia are discusses the production of WBCs and their kinetic functions.

xi
xii Preface

Chapter 13 provides detail on platelet production, structure, Part VI: Hematology in Selected Populations
and function including adhesion, aggregation, and activation. Chapter 38, newly written, provides valuable laboratory infor-
mation on the hematology of the pediatric and geriatric
Part III: Routine Laboratory Evaluation of populations.
Blood Cells
Chapter 14 describes time-honored manual hematologic Part VII: Cell-Counting Automation
procedures that are employed daily such as manual cell counts, Chapter 39 reviews current automated hematology analyzers.
hemoglobin, and hematocrit determinations and compares
them to current point-of-care technology. Chapter 15 describes Part VIII: Hemostasis and Thrombosis
peripheral blood film preparation examination and peripheral Chapter 40 provides the coagulation cascade mechanism and
blood cell morphology. Chapter 16 follows up with bone relates it to current cell-based hemostasis models. Chapter 41
marrow aspirate and biopsy collection, preparation, examina- details hemorrhagic disorders, newly expanded to include
tion, and reporting. Chapter 17 describes the methods for management of the acute coagulopathy of trauma and shock.
analyzing the normal and pathological cells of cerebrospinal Chapter 42 describes laboratory tests that predict and monitor
fluid, joint fluid, transudates, and exudates, illustrated with thrombotic diseases of the arteries and veins. Chapters 43 and
many excellent photomicrographs. 44 describe quantitative and qualitative platelet disorders, and
Chapter 45 details laboratory assays of platelets and the coagu-
Part IV: Hematopathology: lation mechanism. Chapter 46 expands on Chapter 45 with
Erythrocyte Disorders details for monitoring antithrombotic drugs, including the
Chapter 18 provides an overview of anemia, which is the most latest oral anticoagulants and a variety of antiplatelet drugs,
common hematologic disorder, and integrates peripheral and Chapter 47 reviews automated coagulation analyzers and
blood and bone marrow morphology with red blood cell bench-top point of care instrumentation.
indices, reticulocyte counts, and interpretation of pathologic
red blood cell morphology. Chapters 19 to 21 describe disor-
READERS
ders of iron and DNA metabolism, and bone marrow failure.
Chapters 22 to 25, fully revised, provide the hemolytic anemias Hematology: Clinical Principles and Applications is written for
(anemias of shortened red blood cell life span) that are caused Medical Laboratory Scientists, Medical Laboratory Technicians,
by intrinsic or extrinsic defects. Chapters 26 and 27 provide and the faculty of Medical Laboratory Science and Medical
updates in pathophysiology and address the latest advance- Laboratory Technician educational programs. It is a valuable
ments in the diagnosis and treatment of hemoglobinopathies, study guide for pathology and hematology-oncology residents
such as sickle cell disease, and the thalassemias. and fellows and a valuable shelf reference for hematologists,
pathologists, and hematology and hemostasis laboratory
Part V: Leukocyte Disorders managers.
Chapter 28 addresses nonmalignant systemic disorders that
are reflected in the distribution of peripheral blood white
TEXTBOOK FEATURES
blood cells. These include bacterial and viral infections,
systemic disorders reflected in abnormal white blood cell Hematology: Clinical Principles and Applications is logically orga-
morphology, infectious mononucleosis, and the blood cell nized and reflects the practical clinical expertise of its authors.
effects of benign lymphoproliferative disorders. There are The text is enhanced by full-color, color-balanced digital
many new, color-balanced digital photomicrographs. Chapter photomicrographs, figures and line art, and detailed text boxes
29 introduces the pathologic mechanisms of white blood and tables. Figures and tables are enhanced with stand-alone
cell neoplasms (malignancy) and Chapters 30 to 33 provide captions. Pedagogy is supported by learning objectives, real-life
updated details on time-honored but still effective cyto introductory case studies with open-ended discussion ques-
chemistry; cytogenetic procedures, which now include fluores- tions, comprehensive summaries, and study questions at the
cence in situ hybridization; and molecular diagnostics, with end of each chapter. Students preparing for examinations may
emphasis on end-point and real-time polymerase chain use the learning objectives, review questions, and chapter sum-
reaction, microarrays, and gene sequencing. Chapter 33 maries to guide their test preparation. The appendix provides
describes the technology of flow cytometry and its diagnostic examples of material safety data sheets, answers to the case
applications, includes the detection of current and emerging study questions and review questions, and an extensive, fully
phenotypic markers. The chapter provides numerous exam- updated glossary.
ples of scatterplot results in normal and leukemic conditions.
Chapters 34 to 37 provide the latest worldwide classifica-
NEW TO THIS EDITION
tions and pathophysiologic models for myeloproliferative
neoplasms, myelodysplastic syndromes, acute lymphoblastic Editor Bernadette Rodak, MS, MLS Indiana University
and myeloblastic leukemias, chronic lymphocytic leukemia, School of Medicine, who has been the lead editor for the
and solid tumor lymphoid neoplasms such as lymphoma and first three editions, and George A. Fritsma, MS, MLS,
myeloma. University of Alabama at Birmingham Department of
 Preface xiii

Pathology, co-editor of the third edition, are joined for the A bulleted summary at the end of each chapter that provides
fourth edition by Elaine M. Keohane, PhD, MLS, University a comprehensive review of essential material.
of Medicine and Dentistry of New Jersey Department of Review questions at the end of each chapter that are written
Clinical Laboratory Sciences. to match the chapter objectives; they are given in the format
Co-editor George A. Fritsma, proprietor of the blog The used by certification examinations.
Fritsma Factor, Your Interactive Hemostasis Reference, spon-
sored by Precision BioLogic, Dartmouth, Nova Scotia,
rewrote Chapter 5, Quality Assurance in Hematology and
EVOLVE ANCILLARIES
Hemostasis Testing; and Chapter 16, Bone Marrow Exami-
nation. Prof. Fritsma continues as editor of Part VIII: Hemo- For the Instructor
stasis and Thrombosis. Test bank: An ExamView test bank of 850 multiple-choice
Chapter 47, Coagulation Instrumentation, has been com- questions features rationales, cognitive levels, and page
pletely updated by internationally recognized hemostasis number references to the text. Available for in-class review
researcher David McGlasson, Wilford Hall USAF Hospital, or for test development.
San Antonio, Texas. Instructors manual: The instructors manual includes one
Substantial updates were made to Chapter 29, Introduction chapter for every chapter in the text and contains key terms,
to Leukocyte Neoplasms, by Peter D. Emanuel, MD, Direc- objectives, outlines, and study questions. This can be used
tor, Winthrop P. Rockefeller Cancer Institute, Professor of in preparation for classes and during lecture.
Medicine, Kent Westbrook, MD Endowed Chair, University Case studies: 54 case studies feature photomicrographs,
of Arkansas for Medical Sciences, Little Rock, Arkansas. images, and discussion questions. These can be used in class
Dr. Keohane provided substantial updates to Chapters 23 for review of material, for practical exams, or for students
to 25, on the Hemolytic Anemias. class presentations.
Substantial updates in Chapter 20, Anemias Caused by PowerPoint presentations: One PowerPoint presentation
Defects of DNA Metabolism, and Chapter 38, Pediatric and per chapter can be used as is or as a template to prepare
Geriatric Hematology, by Linda H. Goossen, PhD, MT lectures.
(ASCP), College of Health Professions, Grand Valley State Image Collection: All of the images from the book are avail-
University, Grand Rapids, Michigan. able as electronic files that can be downloaded into Power-
Point presentations. These can be used during lecture to
illustrate important concepts.
PEDAGOGY
For the Student
Each chapter contains: Glossary: The glossary is available on the Evolve site and
Learning objectives for all cognitive domains. can be used as a quick reference to look up unfamiliar terms
One or two case studies at the beginning of each chapter electronically.
that pique the readers interest and provide open-ended Weblinks: Links to places of interest on the web specifically
discussion questions. for hematology.
 Acknowledgments

Editors Elaine Keohane and George Fritsma respectfully Roslyn McQueen, Rakesh Mehta, Martha Miers, Carole Mullins,
acknowledge Bernadette F. (Bunny) Rodak, who first under- Martha Payne, Keila Poulsen, Tim Randolph, Vishnu Reddy,
stood the need for an accessible clinical laboratory hematology Larry Smith, Anne Stiene-Martin, Gail Vance, and Karen
text in 1992. Through Bunnys perseverance, Hematology: Clini- Bourlier Waldron.
cal Principles and Applications has grown to a worldwide educa- We also express personal appreciation to Ellen Wurm-
tional resource and reference for pathology and hematology Cutter, Elsevier managing editor, who has responsibly and pro-
practitioners, residents, and fellows; medical laboratory scien- fessionally managed production through three editions. Ellens
tists; and medical laboratory science students. Now in this, its professional support, prompts, and nudges kept the project on
fourth edition, the Rodak hematology text continues to lead track. We are grateful to David Stein, Catherine Jackson, and
in its contributions to clinical laboratory science and labora- Janet Lincoln for their valued editorial assistance.
tory and clinical hematology. Finally, we acknowledge the contributions of newly invited
The editors acknowledge the authors who have made and fourth edition authors, fourth edition editor Elaine Keohane,
continue to make significant contributions. These include authors who contributed manuscripts to previous editions, and
Kathryn Doig, co-editor of the third edition; Ann Bell, Larry our friends and professional colleagues who have encouraged
Brace, Carol Bradford, Sarah Burns, Michelle Butina, the late this project through the years.
Deanne Chapman, Karen Clark, Mary Coleman, Leilani Collins,
Magdalena Czader, Peter Emanuel, Sheila Finch, Margaret
Fritsma, Linda Goossen, John Griep, Teresa Hippel, Cynthia Bernadette F. Rodak, MS, MLS
Johns, John Krause, Mark Lasbury, Susan Leclair, Sharral George A. Fritsma, MS, MLS
Longanbach, Lynn Maedel, Dave McGlasson, Marisa Marques, Elaine M. Keohane, PhD, MLS

xiv
 Contents

PART I Introduction to Hematology PART III Routine Laboratory Evaluation of

Blood Cells
CHAPTER 1 An Overview of Clinical Laboratory Hematology, 1
George A. Fritsma CHAPTER 14 Routine and Point-of-Care Testing in Hematology:
Manual and Semiautomated Methods, 172
CHAPTER 2 Safety in the Hematology Laboratory, 7 Karen S. Clark and Teresa G. Hippel
Sheila A. Finch
CHAPTER 15 Examination of the Peripheral Blood Film and
CHAPTER 3 Specimen Collection, 18 Correlation with the Complete Blood Count, 192
Carole A. Mullins Lynn B. Maedel and Kathryn Doig

CHAPTER 4 Care and Use of the Microscope, 32 CHAPTER 16 Bone Marrow Examination, 210
Bernadette F. Rodak George A. Fritsma

CHAPTER 5 Quality Assurance in Hematology and Hemostasis CHAPTER 17 Body Fluids in the Hematology Laboratory, 226
Testing, 41 Leilani Collins
George A. Fritsma

PART IV Hematopathology:
PART II Hematopoiesis Erythrocyte Disorders

CHAPTER 6 Cellular Structure and Function, 57 CHAPTER 18 Anemias: Red Blood Cell Morphology and
Keila B. Poulsen Approach to Diagnosis, 241
Rakesh P. Mehta
CHAPTER 7 Hematopoiesis, 66
Larry Smith CHAPTER 19 Disorders of Iron and Heme Metabolism, 253
Kathryn Doig
CHAPTER 8 Erythrocyte Production and Destruction, 86
Kathryn Doig CHAPTER 20 Anemias Caused by Defects of DNA
Metabolism, 268
CHAPTER 9 Energy Metabolism and Membrane Physiology of Linda H. Goossen
the Erythrocyte, 103
Kathryn Doig and George A. Fritsma CHAPTER 21 Bone Marrow Failure, 283
Elaine M. Keohane
CHAPTER 10 Hemoglobin Metabolism, 115
Mary Coleman CHAPTER 22 Introduction to Increased Destruction of
Erythrocytes, 299
CHAPTER 11 Iron Metabolism, 126 Kathryn Doig
Mary Coleman
CHAPTER 23 Intrinsic Defects Leading to Increased Erythrocyte
CHAPTER 12 Leukocyte Development, Kinetics, and Destruction, 314
Functions, 134 Elaine M. Keohane
Anne Stiene-Martin
CHAPTER 24 Extrinsic Defects Leading to Increased Erythrocyte
CHAPTER 13 Platelet Production, Structure, and Function, 152 DestructionNonimmune Causes, 337
George A. Fritsma Elaine M. Keohane

xv
xvi Contents

CHAPTER 25 Extrinsic Defects Leading to Increased Erythrocyte

DestructionImmune Causes, 353
PART VII Cell-Counting Automation
Elaine M. Keohane
CHAPTER 39 Automated Cell-Counting Instrumentation, 598
Sharral Longanbach, Deanne H. Chapman, and
CHAPTER 26 Hemoglobinopathies (Structural Defects in
Martha K. Miers
Hemoglobin), 366
Tim R. Randolph

CHAPTER 27 Thalassemias, 390

PART VIII Hemostasis and Thrombosis
Rakesh P. Mehta and Elaine M. Keohane
CHAPTER 40 Normal Hemostasis and Coagulation, 626
Margaret G. Fritsma and George A. Fritsma
PART V Leukocyte Disorders
CHAPTER 41 Hemorrhagic Coagulation Disorders, 647
George A. Fritsma
CHAPTER 28 Nonmalignant Leukocyte Disorders, 408
Anne Stiene-Martin
CHAPTER 42 Thrombosis Risk Testing, 668
George A. Fritsma
CHAPTER 29 Introduction to Leukocyte Neoplasms, 427
Peter D. Emanuel
CHAPTER 43 Thrombocytopenia and Thrombocytosis, 694
Larry D. Brace
CHAPTER 30 Cytochemistry, 436
Bernadette F. Rodak
CHAPTER 44 Qualitative Disorders of Platelets and
Vasculature, 718
CHAPTER 31 Cytogenetics, 445
Larry D. Brace
Gail H. Vance

CHAPTER 45 Laboratory Evaluation of Hemostasis, 734

CHAPTER 32 Molecular Diagnostics in the Clinical
George A. Fritsma
Laboratory, 461
Mark E. Lasbury
CHAPTER 46 Monitoring Antithrombotic Therapies, 765
George A. Fritsma
CHAPTER 33 Flow Cytometric Analysis in Hematologic
Disorders, 488
CHAPTER 47 Coagulation Instrumentation, 783
Magdalena Czader
David L. McGlasson
CHAPTER 34 Myeloproliferative Neoplasms, 508
Tim R. Randolph
APPENDIX
CHAPTER 35 Myelodysplastic Syndromes, 533
Material Safety Data Sheet, 796
Bernadette F. Rodak

Answers, 801
CHAPTER 36 Acute Leukemias, 546
Susan J. Leclair and Bernadette F. Rodak
Glossary, 816
CHAPTER 37 Mature Lymphoid Neoplasms, 558
Magdalena Czader

PART VI Hematology in Selected Populations

CHAPTER 38 Pediatric and Geriatric Hematology, 580

Linda H. Goossen
 PART I Introduction to Hematology
CHAPTER 1 An Overview of Clinical Laboratory Hematology 1

An Overview of Clinical
Laboratory Hematology