1 Daniel A. Arber MD Professor and Vice Chair Department of Pathology Stanford University Director of Anatomic and Clinical Pathology Services Stanford University Medical Center Stanford, California Bertil Glader MD, PhD Alan F. List MD Senior Member Department of Malignant Hematology President and CEO Moffitt Cancer Center Tampa, Florida Robert T. Means, Jr., MD Professor of Internal Medicine Executive Dean University of Kentucky College of Medicine Lexington, Kentucky Frixos Paraskevas MD Professor of Internal Medicine and Immunology (Retired) University of Manitoba Medical School Associate Member Institute of Cell Biology—Cancer Care Manitoba Winnipeg, Manitoba, Canada George M. Rodgers MD, PhD Professor of Medicine and Pathology University of Utah School of Medicine Health Sciences Center Medical Director, Coagulation Laboratory ARUP Laboratories Salt Lake City, Utah John Foerster MD, FRCPC Contributors Associate Professor Department of Pediatrics University of Saskatchewan Saskatoon, Saskatchewan Canada Archana M. Agarwal, MD Assistant Professor Department of Pathology University of Utah Medical Director Special Genetics ARUP Laboratories Salt Lake City, Utah Blanche P. Alter, MD, MPH Senior Clinician Clinical Genetics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute Rockville, Maryland Claudio Anasetti, MD Professor Oncologic Sciences University of South Florida Senior Member Department Chair Department of Blood and Marrow Transplantation H. Lee Moffitt Cancer Center Tampa, Florida Stephen M. Ansell, MD, PhD Professor of Medicine Mayo Clinic College of Medicine Consultant Division of Hematology Department of Internal Medicine Mayo Clinic Rochester, Minnesota Daniel A. Arber, MD Professor and Vice Chair Department of Pathology Stanford University Director of Anatomic and Clinical Pathology Services Wintrobe's Clinical Hematology 13th Edition 2 Robert J. Arceci, MD, PhD Professor Department of Pediatric Oncology Johns Hopkins University Baltimore, Maryland Donald M. Arnold, MD, MSc Associate Professor Department of Medicine McMaster University Associate Medical Director Medical Affairs Canadian Blood Services Hamilton, Ontario Canada Maria R. Baer, MD Professor Department of Medicine University of Maryland School of Medicine Director Hematologic Malignancies University of Maryland Marlene and Stewart Greenebaum Cancer Center Baltimore, Maryland Charles D. Bangs, BS Kirstin F. Barnhart, DVM, PhD, DACVP Principal Pathologist AbbVie, Inc. Preclinical Safety North Chicago, Illinois James C. Barton, MD Clinical Professor of Medicine Department of Medicine University of Alabama at Birmingham Medical Director Southern Iron Disorders Center Brookwood Medical Center Birmingham, Alabama Minoo Battiwalla, MD, MS Staff Clinician, Hematology Branch National Heart, Lung and Blood Institute National Institutes of Health Bethesda, Maryland A. Dean Befus, PhD Professor Department of Medicine University of Alberta Edmonton, Alberta Canada P. Leif Bergsagel, MD Professor College of Medicine Mayo Clinic Medical School Rochester, Minnesota Department of Hematology/Oncology Mayo Clinic Phoenix, Arizona Nancy Berliner, MD Professor Department of Medicine Harvard Medical School Chief Division of Hematology Department of Medicine Brigham and Women's Hospital Boston, Massachusetts Kristie A. Blum, MD Associate Professor Division of Hematology, Internal Medicine The Ohio State University The Ohio State University Wexner Medical Center Columbus, Ohio Caterina Borgna-Pignatti, MD Full Professor of Pediatrics Clinical and Experimental Medicine University of Ferrara Chief Department of Pediatrics Arcispedale Sant'Anna Ferrara, Italy Linette Bosques, MPhil PhD Candidate Departments of Cell Biology and Pathology Yale School of Medicine New Haven, Connecticut Sylvia S. Bottomley, MD Professor Emeritus of Medicine Department of Medicine University of Oklahoma College of Medicine Staff Physician Medical Service VA Medical Center Oklahoma City, Oklahoma Robert A. Brodsky, MD 3 Professor of Medicine and Oncology Division of Hematology Department of Medicine Director Division of Hematology Johns Hopkins University Baltimore, Maryland Kathleen E. Brummel-Ziedins, PhD Francis K. Buadi, MD, ChB Assistant Professor Consultant Hematologist Department of Internal Medicine Mayo Clinic Rochester, Minnesota David C. Calverley, MD Ralph Carmel, MD Professor of Medicine Department of Medicine Weill Cornell Medical College New York, New York Director of Research Department of Medicine New York Methodist Hospital Brooklyn, New York Howard H. W. Chan, MBChB, FRCP(C), MSC Assistant Professor Department of Medicine McMaster University Hamilton, Ontario Canada Karen L. Chang, MD William C. Chapman, MD Professor of Surgery Department of Surgery Washington University—St. Louis Attending/Chief of Surgery Department of Surgery Barnes Jewish Hospital St. Louis, Missouri Athena M. Cherry, PhD Andrew Chow, BA MD-PhD Candidate Stem Cell Institute Albert Einstein College of Medicine New York, New York Robert D. Christensen, MD Matthew Collin, BM, BCh, DPhil, FRCPath Professor of Hematology Institute of Cellular Medicine Newcastle University Consultant Hematologist Northern Centre for Cancer Care Newcastle upon Tyne Hospitals Newcastle upon Tyne, United Kingdom Steven E. Coutre, MD Utpal P. Davé, MD Michael W. N. Deininger, MD, PhD M.M. Wintrobe Professor of Medicine Chief, Division of Hematology and Hematologic Malignancies Department of Internal Medicine Wintrobe's Clinical Hematology 13th Edition 4 Judah A. Denburg, MD, FRCPC William J. Walsh Professor of Medicine Department of Medicine McMaster University Hamilton, Ontario Canada Robert J. Desnick, PhD, MD Dean for Genetic and Genomic Medicine Professor and Chairman Emeritus Genetic and Genomic Sciences Mount Sinai School Medicine Physician-in-Chief Genetics and Genomic Medicine Mount Sinai Hospital New York, New York David Dingli, MD, PhD Professor of Medicine Hematology and Internal Medicine Mayo Clinic College of Medicine Consultant, Hematology Mayo Clinic Rochester, Minnesota Angela Dispenzieri, MD Professor of Medicine and Laboratory Medicine Department of Medicine Mayo College of Medicine Mayo Clinic Rochester, Minnesota Ahmet Dogan, MD, PhD Professor of Pathology Department of Laboratory Medicine and Pathology Mayo Medical School Consultant Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, Minnesota M.B. Majella Doyle, MD Assistant Professor of Surgery Department of Surgery Washington University—St. Louis Attending, Department of Surgery Barnes Jewish Hospital St. Louis, Missouri P.ix Cynthia E. Dunbar, MD Senior Investigator and Section Head Hematology Branch The National Heart, Lung and Blood Institute National Institutes of Health Bethesda, Maryland Anne F. Eder, MD, PhD Executive Medical Officer National Headquarters, Biomedical Services American Red Cross Rockville, Maryland Adjunct Assistant Professor Department of Pathology and Laboratory Medicine Georgetown University School of Medicine Washington, D.C. Corwin Q. Edwards, MD Professor of Medicine Department of Medicine University of Utah School of Medicine Director of Graduate Medical Education Intermountain Medical Center and LDS Hospital Salt Lake City, Utah Ashkan Emadi, MD, PhD Stephen J. Everse, PhD Rafael Fonseca, MD Magali J. Fontaine, MD, PhD Assistant Professor Department of Pathology Stanford University Associate Medical Director Department of Pathology, Transfusion Service Stanford, California Haydar Frangoul, MD 5 Paul S. Frenette, MD Chair and Director Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Albert Einstein College of Medicine New York, New York Richard C. Friedberg, MD, PhD Professor and Deputy Chairman Department of Pathology Tufts University School of Medicine Western Campus Chair Department of Pathology Baystate Medical Center Springfield, Massachusetts Debra L. Friedman, MD, MS Associate Professor Department of Pediatrics Vanderbilt University School of Medicine Director, Division of Pediatric Hematology/Oncology Monroe Carell Jr. Children's Hospital at Vanderbilt Nashville, Tennessee Michael M. Fry, DVM, MS, DACVP Associate Professor Department of Biomedical and Diagnostic Sciences College of Veterinary Medicine, University of Tennessee Knoxville, Tennessee Vijayakrishna K. Gadi, MD, PhD Assistant Member Clinical Research Division Fred Hutchinson Cancer Research Center Assistant Professor Medical Oncology University of Washington Seattle, Washington Renzo Galanello, MD Professor of Pediatrics Department of Biomedical Sciences and Biotechnologies University of Cagliari Head, 2nd Pediatric Clinic Thalassemia Unit Cagliari, Italy Susan A. Galel, MD Patrick G. Gallagher, MD Professor Department of Pediatrics and Genetics Yale University School of Medicine Attending Physician Yale—New Haven Hospital New Haven, Connecticut Jacob R. Garcia, MD Guillermo Garcia-Manero, MD Professor Department of Leukemia University of Texas MD Anderson Cancer Center Houston, Texas Amy E. Geddis, MD, PhD Associate Professor Pediatric Hematology/Oncology University of Southern California, San Diego Rady Children's Hospital San Diego San Diego, California Tracy I. George, MD Morie A. Gertz, MD, MACP Professor and Chair Department of Medicine Mayo Clinic Rochester, Minnesota P.x Professor Biochemistry and Medical Genetics Manitoba Institute of Cell Biology University of Manitoba Wintrobe's Clinical Hematology 13th Edition 6 Provincial Director of Research Manitoba Institute of Cell Biology CancerCare Manitoba Winnipeg, Manitoba Canada Bertil Glader, MD, PhD Christopher L. Gonzalez, MD Lawrence T. Goodnough, MD Siamon Gordon, MB, ChB, PhD, FRS Glaxo Professor of Cellular Pathology Emeritus Sir William Dunn School of Pathology University of Oxford Oxford, United Kingdom Jason Gotlib, MD, MS John P. Greer, MD Michael R. Grever, MD Professor Department of Internal Medicine The Ohio State University Chairman Department of Internal Medicine Arthur G. James Cancer Hospital and Richard J. Solove Research Institute Columbus, Ohio Thomas G. Gross, MD, PhD Professor Department of Pediatrics The Ohio State University Medical Center Gordon Teter Chair for Pediatric Cancer Hematology/Oncology/BMT Nationwide Children's Hospital Columbus, Ohio Roy M. Gulick, MD Professor Department of Medicine Chief, Division of Infectious Disease Weill Cornell Medical College New York, New York Kenneth R. Hande, MD Jane S. Hankins, MD, MS Associate Member Hematology St. Jude Children's Research Hospital Memphis, Tennessee Suzanne R. Hayman, MD Nancy M. Heddle, MSc Derralynn A. Hughes, MA, DPhil, FRCP, FRCPath Senior Lecturer Department of Haematology University College London London, United Kingdom Caron A. Jacobson, MD 7 Madan Jagasia, MBBS, MS Vandita P. Johari, MD Assistant Professor Department of Pathology Tufts University School of Medicine Western Campus Chief, Clinical Pathology Department of Pathology Baystate Health Springfield, Massachusetts James B. Johnston, MD Dan Jones, PhD Adetola A. Kassim, MD John G. Kelton, MD Dean and Vice President Faculty of Health Sciences Professor Department of Pathology and Molecular Medicine and Department of Medicine McMaster University Hamilton, Ontario Canada P.xi Assistant Professor Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville, Tennessee Rami Komrokji, MD Clinical Director Associate Member Department of Malignant Hematology H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida Ashish Kumar, MD, PhD Assistant Professor of Pediatrics Division of Bone Marrow Transplantation and Immune Deficiency University of Cincinnati College of Medicine Staff Physician Division of Bone Marrow Transplantation and Immune Deficiency Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center Cincinnati, Ohio Shaji Kumar, MD Professor of Medicine Division of Hematology Mayo Clinic Rochester, Minnesota Thomas J. Kunicki, PhD Senior Scientist II Department of Hematology Research CHOC Children's Hospital University of California—Irvine Orange, California Gary M. Kupfer, MD Professor Department of Pediatrics Yale School of Medicine Chief, Pediatric Hematology/Oncology Department of Pediatrics Yale New Haven Children's Hospital New Haven Connecticut Paul J. Kurtin, MD 8 Professor of Pathology Mayo Medical School Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, Minnesota Larry W. Kwak, MD, PhD Professor and Chairman Department of Lymphoma/Myeloma The University of Texas MD Anderson Cancer Center Houston, Texas Robert A. Kyle, MD Professor of Medicine Laboratory Medicine and Pathology Department of Internal Medicine Division of Hematology College of Medicine Mayo Clinic Rochester, Minnesota Paige Lacy, PhD Martha Q. Lacy, MD Jeffrey E. Lancet, MD Associate Professor University of South Florida Section Chief—Leukemia Associate Member of Malignant Hematology/Oncology H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida Andre Larochelle, MD, PhD Principal Investigator, Hematology Branch The National Heart, Lung and Blood Institute National Institutes of Health Bethesda, Maryland Christopher M. Lehman, MD Professor (Clinical) Pathology Department University of Utah Medical Director of Hospital Laboratories Pathology Department University of Utah Health Care Salt Lake City, Utah Meghan S. Liel, MD Fellow Department of Hematology and Medical Oncology Oregon Health and Science University Portland, Oregon Jeffrey M. Lipton, MD, PhD Professor Pediatrics and Molecular Medicine Hofstra North Shore—LIJ School of Medicine Hempstead, New York Chief Hematology/Oncology and Stem Cell Transplantation Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park, New York Frederick L. Locke, MD Assistant Professor Oncologic Sciences University of South Florida Assistant Member Blood and Marrow Transplantation H. Lee Moffitt Cancer Center Tampa, Florida Mignon Lee-Chuen Loh, MD John A. Lust, MD, PhD Associate Professor of Medicine Mayo Clinic College of Medicine Consultant Division of Hematology Department of Internal Medicine Mayo Clinic Rochester, Minnesota William R. Macon, MD Professor of Pathology Mayo Medical School Consultant Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, Minnesota Suman Malempati, MD Kenneth G. Mann, PhD 9 P.xii Catherine A. Manno, MD Chair Department of Pediatrics Pat and John Rosenwald Professor of Pediatrics New York University Langone Medical Center New York, New York Peter Maslak, MD Professor of Clinical Medicine Department of Internal Medicine Weill Cornell Medical College Chief Hematology Laboratory Service Laboratory Medicine Memorial Sloan-Kettering Cancer Center New York, New York Thomas L. McCurley, MD Laura Y. McGirt, MD Margaret M. McGovern, MD, PhD Professor and Chair Department of Pediatrics Stony Brook University School of Medicine Physician in Chief Stony Brook Long Island Children's Hospital Stony Brook, New York Kelly M. McNagny Professor Medical Genetics The Biomedical Research Centre University of British Columbia Vancouver, British Columbia Canada Robert T. Means, Jr., MD Professor of Internal Medicine Executive Dean University of Kentucky College of Medicine Lexington, Kentucky Dean D. Metcalfe, MD Chief Laboratory of Allergic Diseases Division of Intramural Research National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, Maryland Joseph R. Mikhael, MD Andrew J. Moore, MD Redwan Moqbel, PhD, FRCPath Professor and Head Department of Immunology Faculty of Medicine University of Manitoba Winnipeg, Manitoba, Canada David S. Morgan, MD William G. Morice, II MD, PhD Associate Professor Laboratory Medicine and Pathology Mayo School of Graduate Medical Education Consultant Division of Hematopathology Department of Laboratory Medicine and Pathology Mayo Clinic Rochester, Minnesota Claudio A. Mosse, MD, PhD Assistant Professor of Pathology Department of Pathology Vanderbilt University School of Medicine Chief of Pathology and Laboratory Medicine Department of Pathology and Laboratory Medicine Tennessee Valley Health Systems VA Nashville, Tennessee Wintrobe's Clinical Hematology 13th Edition 10 Sattva S. Neelapu, MD Associate Professor Department of Lymphoma and Myeloma The University of Texas MD Anderson Cancer Center Houston, Texas Elizabeta Nemeth, PhD Associate Professor Department of Medicine David Geffen School of Medicine University of California, Los Angeles Los Angeles, California Huong (Marie) Nguyen, MD H. Stacy Nicholson, MD, MPH Professor and Chair Department of Pediatrics Oregon Health and Science University Physician-in-Chief Doernbecher Children's Hospital Portland, Oregon Ariela Noy, MD Associate Member, Associate Attending Department of Medicine Memorial Sloan-Kettering Cancer Center and Cornell Weill Medical College New York, New York Diane J. Nugent, MD P.xiii Robin K. Ohls, MD Professor Department of Pediatrics University of New Mexico Director of Pediatric Integration Clinical Translational Science Center University of New Mexico Health Sciences Center Albuquerque, New Mexico Mihaela Onciu, MD Professor of Pathology and Laboratory Medicine Vice Chair for Hematopathology Department of Pathology and Laboratory Medicine Weill Cornell Medical College Director Division of Hematopathology Department of Pathology and Laboratory Medicine New York, New York Thomas Orfeo, PhD Eric Padron, MD Assistant Member Department of Malignant Hematology H. Lee Moffitt Cancer Center & Research Institute Tampa, Florida Frixos Paraskevas, MD Professor of Internal Medicine and Immunology (Retired) University of Manitoba Medical School Associate Member Institute of Cell Biology—Cancer Care Manitoba Winnipeg, Manitoba Canada Wintrobe's Clinical Hematology 13th Edition 11 Charles J. Parker, MD Professor Department of Medicine University of Utah School of Medicine Salt Lake City, Utah Robert C. Pendleton, MD, FACP Associate Professor Department of Medicine University of Utah Director Hospitalist Program Medical Director Thrombosis Service Department of Medicine University of Utah Healthcare Salt Lake City, Utah Sherrie L. Perkins, MD, PhD Professor of Hematology Department of Pathology University of Utah Salt Lake City, Utah Joseph Pidala, MD, MS Assistant Professor Oncologic Sciences College of Medicine—University of South Florida Assistant Member Blood and Marrow Transplantation H. Lee Moffitt Cancer Center Tampa, Florida Annette Plüddemann, PhD Senior Researcher Department of Primary Care Health Sciences University of Oxford Oxford, United Kingdom Michael R. Porembka, MD Department of Surgery Washington University School of Medicine St. Louis, Missouri Anna Porwit, MD, PhD Jerry S. Powell, MD John G. Quigley, MB, FRCPC Associate Professor Department of Medicine University of Illinois at Chicago Attending Physician Division of Hematology/Oncology Department of Medicine University of Illinois Hospital and Health Sciences System Chicago, Illinois Charles T. Quinn, MD, MS Associate Professor Department of Pediatrics University of Cincinnati College of Medicine Director of Hematology Clinical and Translational Research Department of Hematology Cincinnati Children's Hospital Medical Center Cincinnati, Ohio Elizabeth A. Raetz, MD S. Vincent Rajkumar, MD Professor of Medicine Division of Hematology Mayo Clinic Rochester, Minnesota Michael Recht, MD, PhD Nishitha M. Reddy, MD Matthew M. Rees, MD P.xiv 12 George M. Rodgers, MD, PhD Professor of Medicine and Pathology University of Utah School of Medicine Health Sciences Center Medical Director Coagulation Laboratory ARUP Laboratories Salt Lake City, Utah Stephen J. Russell, MD, PhD Dean for Discovery and Experimental Research Department of Molecular Medicine Richard O. Jacobson Professor of Molecular Medicine Mayo Clinic Rochester, Minnesota John T. Sandlund, Jr., MD Member Department of Oncology St. Jude Children's Research Hospital Professor Department of Pediatrics University of Tennessee College of Medicine Memphis, Tennessee Bipin N. Savani, MBBS Associate Professor of Medicine Director Long Term Transplant Clinic, Hematology and Stem Cell Transplant Vanderbilt University Medical Center Nashville, Tennessee Matthew Seftel, MD Paul J. Shami, MD Luke R. Shier, MD Akiko Shimamura, MD, PhD Keith M. Skubitz, MD James W. Smith, MT, BSc Assistant Professor Department of Medicine McMaster University Coordinator/Technical Director Platelet Immunology Laboratory Hamilton Health Sciences Hamilton, Ontario Canada Kristi J. Smock, MD Susan S. Smyth, MD, PhD Professor and Chief Division of Cardiovascular Medicine University of Kentucky Attending Physician Medical Services Lexington VA Medical Center Lexington, Kentucky Wintrobe's Clinical Hematology 13th Edition 13 Nicole I. Stacy, DVM, DrMedVet Adjunct Clinical Assistant Professor Department of Large Animal Clinical Sciences University of Florida College of Veterinary Medicine Gainesville, Florida Martin H. Steinberg, MD Professor of Medicine Department of Pediatrics, Pathology and Laboratory Medicine Boston University School of Medicine Director Center of Excellence in Sickle Cell Disease Boston Medical Center Boston, Massachusetts A. Keith Stewart, MBChB Stephen A. Strickland, MD, MSCI Assistant Professor Department of Medicine Division of Hematology/Oncology Vanderbilt University Medical Center Nashville, Tennessee Mary Ann Thompson, MD, PhD Associate Professor Department of Pathology Vanderbilt University Medical Center Nashville, Tennessee John Tisdale, MD Senior Investigator and Section Head Hematology Branch The National Heart, Lung and Blood Institute National Institutes of Health Bethesda, Maryland Troy R. Torgerson, MD, PhD Assistant Professor Department of Pediatrics University of Washington School of Medicine Attending Physician Department of Immunology Seattle Children's Hospital Seattle, Washington P.xv Professor Department of Medicine Pennsylvania State University College of Medicine Chief Section of Hemostasis and Thrombosis Milton S. Hershey Medical Center Hershey, Pennsylvania Luc Van Kaer, MD Srdan Verstovsek, MD, PhD Professor of Medicine Chief Section for Myeloproliferative Neoplasms (MPNs) Department of Leukemia Director Clinical Research Center for MPNs University of Texas MD Anderson Cancer Center Houston, Texas Maurene K. Viele, MD Mary A. Vu, MD Mark C. Walters, MD Winfred C. Wang, MD 14 Member Department of Hematology St. Jude Children's Research Hospital Memphis, Tennessee Russell E. Ware, MD, PhD Professor and Vice-Chair for Global Health Department of Pediatrics Baylor College of Medicine Director Texas Children's Hematology Center Director Texas Children's Center for Global Health Texas Children's Hospital Houston, Texas Kathryn E. Webert, MD, MSc, FRCPC Associate Professor Department of Medicine and Department of Molecular Medicine and Pathology McMaster University Director of Operations, Transfusion Medicine Hamilton Regional Laboratory Medicine Program Hamilton Health Sciences Hamilton, Ontario Canada Lawrence M. Weiss, MD James A. Whitlock, MD Professor Department of Pediatrics University of Toronto Division Head Division of Hematology/Oncology The Hospital for Sick Children Toronto, Ontario Canada Michael E. Williams, MD Byrd S. Leavell Professor of Medicine Hematology/Oncology Division University of Virginia School of Medicine Department of Medicine University of Virginia Health System Charlottesville, Virginia Steven R. Zeldenrust, MD, PhD Assistant Professor Hematology Mayo Clinic Rochester, Minnesota John A. Zic, MD Jeff P. Zwerner, MD, PhD Assistant Professor of Medicine/Dermatology Division of Dermatology Department of Medicine Vanderbilt University School of Medicine Nashville, Tennessee Dedication TO DR. MAXWELL M. WINTROBE…