PREFACEThe 24TH Edition of Goldn's Cecil Medicine symbolizes a time of extra-associate editors-Wendy Levinson,Donald W.Landry,Anil Rustgi,andordinary advances in medicine and in technological innovations for theW.Michael Scheld-we also express our appreciation to Nicholas LaRussodissemination of infortion.This textbook and its associated electronicand other associate editors from the previous editions on whose foundationproducts incorporate the latest medical knowledge in forts that arewe have built.Our returning associate editors-William P.Arend,James O.designed to appeal to learners who prefer to access infortion in a varietyArmitage,David Clemmons,Jeffrey M.Drazen,and Robert C.Griggs-of ways.continue to ke critical contributions to the selection of authors and theThe contents of Cecil have reined true to the tradition of a comprehen-review and approval ofall nuscripts.The editors,however,are fully respon-sive textbook of medicine that carefully explains the why (the underlyingsible for the book as well as the integration among chapters.norl physiology and pathophysiology of disease,now at the cellular andThe tradition of Cecil Medicine is that all chapters are written by distin-molecular as well as the organ level)and the how (now frequently based onguished experts in each field.We are also most grateful for the editorialGrade A evidence from randomized controlled trials).Descriptions of physi-assistance in New York of Theresa Considine and Silva Sergenian.Theseology and pathophysiology include the latest genetic advances in a practicalindividuals and others in our offices have shown extraordinary dedicationfort that strives to be useful to the nonexpert.Medicine has entered an eraand equanimity in working with authors and editors to nage the unendingwhen the acuity of illness and the limited time available to evaluate a patientflow of nuscripts,figures,and permissions.We also thank Faten Aberra,have diminished the ability of physicians to satisfy their intellectual curiosity.Reza Akari,Robert C.Brunham,Ivan Ciric,See Daulat,Gregory F.As a result,the acquisition of infortion,quite easily achieved in this era,isErikson,Kevin Ghassemi,Jason H.Huang,Caron Jacobson,Lisa Kachnic,often confused with knowledge.We have attempted to counteract this tenBryan T.Kelly,Karen Krok,Heather Lehn,Keiron Leslie,Luis Marcos,dency with a textbook that not only informs but also stimulates new ques-Michael Overn,Eric Padron,Bianca Maria Piraccini,Don W.Powell,tions and gives a glimpse of the future path to new knowledge.Grade AKaty Ralston,James M.Swain,Tania Thos,Kirsten Tillisch,Ali Turabi,evidence is specifically highlighted in the text and referenced at the end ofMark Whiteford,and Y.Joseph Woo,who contributed to various chapters.each chapter.In addition to the infortion provided in the textbook,theAt Elsevier,we are most indebted to Dolores Meloni and Linda McKinley,Cecil website supplies expanded content and functionality.In ny cases,theand also thank Cathy Carroll,Taylor Ball,Virginia Wilson,Linda Van Pelt,full articles referenced in each chapter can be accessed from the Cecil website.Suzanne Fannin,and Steve Stave,who have been critical to the planning andThe website is also continuously updated to incorporate subsequent Gradeproduction process under the direction of Mary Gatsch.Many of the clinicalA infortion,other evidence,and new discoveries.photographs were supplied by Charles D.Forbes and William F.Jackson,The sections for each organ system begin with a chapter that sumrizesauthors of Color Atlas and Text of Clinical Medicine,Third Edition,publishedan approach to patients with key symptoms,signs,or laboratory abnorliin 2003 by Elsevier Science Ltd.We thank them for graciously permitting usties associated with dysfunction of that organ system.As sumrized into include their pictures in our book.We have been exposed to rerkableTable 1-1,the text specifically provides clear,concise infortion regardingphysicians in our lifetimes and would like to acknowledge the mentorshiphow a physician should approach more than 100 common symptoms,signs,and support of several of those who exemplify this paradigm-Robert H.and laboratory abnorlities,usually with a flow diagram,a table,or both forGifford,Lloyd H.Smith,Jr,Frank Gardner,and William Castle.Finally,weeasy reference.In this way,Cecil reins a comprehensive text to guide diag-would like to thank the Goldn family-lill,Jeff,Abigail,Mira,Daniel,andnosis and therapy,not only for patients with suspected or known diseases butRobyn Goldn-and the Schafer family-Pauline,Eric,Pam,John,Evso for patients who y have undiagnosed abnorlities that require anand Kate-for their understanding of the time and focus required to edit ainitial evaluation.book that attempts to sustain the tradition of our predecessors and to meetJust as each edition brings new authors,it also reminds us of our gratitudethe needs of today's physician.to past editors and authors.Previous editors of Cecil Medicine include a shortbut rerkably distinguished group ofleaders of American medicine:RussellLEE GOLDMAN,MDCecil,Paul Beeson,Walsh McDermott,James Wyngaarden,Lloyd H.SmithANDREW I.SCHAFER,MDJr.,Fred Plum,I.Claude Bennett,and Dennis Ausiello.As we welcome newCONTENTSSECTION XIV:HEMATOLOGIC DISEASES171 Approach to the Patient with Lymphadenopathy159 Hetopoiesis and Hetopoietic Growth Factors1022and Splenomegaly1107KENNETH KAUSHANSKYJAMES O.ARMITAGE160 The Peripheral Blood Smear1024172 Disorders of Phagocyte Function1111BARBARA⊥.BAINMICHAEL GLOGAUER161 Approach to the Anemias1031173 Eosinophilic Syndromes1118H.FRANKLIN BUNNMARC E.ROTHENBERG162 Microcytic and Hypochromic Anemias1039174 Approach to the Patient with Bleeding and Thrombosis1121GORDON D.GINDERANDREW L SCHAFER163 Autoimmune and Intravascular Hemolytic Anemias1045175 Thrombocytopenia1124ROBERT S.SCHWARTZCHARLES S.ABRAMS164 Hemolytic Anemias:Red Cell Membrane and176 Von Willebrand Disease and Hemorrhagic AbnorlitiesMetabolic Defects1052of Platelet and Vascular Function1131PATRICK G.GALLAGHERWILLIAM L NICHOLS165 The Thalassemias1060177 Hemorrhagic Disorders:Coagulation Factor Deficiencies1137MARIA DOMENICA CAPPELLINIMARGARET V.RAGNI166 Sickle Cell Disease and Other Hemoglobinopathies1066178 Hemorrhagic Disorders:Disseminated IntravascularMARTIN H.STEINBERGCoagulation,Liver Failure,and Vitamin K Deficiency1145ANDREW L SCHAFER167 Megaloblastic Anemias1075ASOK C.ANTONY179 Thrombotic Disorders:Hypercoagulable States1148168 Aplastic Anemia and Related Bone Marrow Failure StatesANDREW I SCHAFER1083GROVER C BAGBY180 Transfusion Medicine1154169 Polycythemias,Essential Thrombocythemia,LAWRENCE T.GOODNOUGHand Priry Myelobfibrosis1090181 Hetopoietic Stem Cell Transplantation1158AYALEW TEFFERIJULIE M.VOSE170 Leukocytosis and Leukopenia1098NANCY BERLINER