2. ANDMana8ement BY
Laboratory
Methods
TWENTY_FIRST EDITION
RichardA. McPhersonMD
HarryP.DaltonProfessor Chairman
and
Division Clinical thol ogy
of Pa
VirginiaCommonwealth niversity;
U
Director
Clinical thol ogy
Pa
M edicalCollege Vir ginia os pi tal s
of H
Richm ond, gin i a, SA
Vir U
Matthe R. PincusMDPhD
Professor
Department Pathology
of
Universitv NewYorkHealthSciences
State of
Center Brooklyn;
at
Ch ai r m an
Department Pathology Laboratory
of and Medicine
New YorkHarborVeteransAffairsHealthCareSystem
Brooklyn
and NewYork, NewYork, USA
ELSEVIER
3. 21st EorrroN
AssocrATr EorroRS
N a i fZ . A b r a h a m r M D P h D
J H. Davis Massey MD PhD
Pathologist,
Staff Director Chemistry,
of Assistant Professor Pathology
of
Hematology,lmmunology, Microbiology
and Vir ginia
Com m onwealth Univer sity
Department Pathology
of VA,
Richm ond, USA
Veterans
Affairs
MedicalCenter;
Assistant
Professor,UpstateMedicalUniversity J o n a t h a n .M i l l e r M D P h D
L
Syracuse, USA
NY Professor ViceChairman
and
Department Pathology
of
M a r t i n H . B l u t hv t o p h o of
TheUniver sity Chicago
Director Research
of lL,
Chicago, USA
Assistant Professor
Departments Surgery Pathology
of and GregoryA. ThreatteMD
SUNYDownstate MedicalCenter Professor Pathology
of
B ro o k l y nN Y U S A
, Director CoreLaboratories Outreach
of and
UpstateMedicalUniversity
R o b e r tE .H u t c h i s o n D
M NY
Syracuse, USA
Professor Pathology,
of Director Clinical
of
Pathology Director Hematopathology
and of E l i z a b e t hU n g e r M D P h D
Department Patho
of logy TeamLeader
Upstate
MedicalUniversity Hum anPapillom avirLabor ator y
us
Syracuse, USA
NY National Center Infectious
for Diseases
Atlanta, CA, USA
M a r k S .L i f s h i t z D
M
Director, inical Laboratories
Cl C a i l L .W o o d s M D
NYU MedicalCenter Professor Pathology
of
ClinicalProfessor, Department Pathology
of Department Pathology
of
Ne wYo r kU n i ve rsi ty ch o oo f Me d i ci ne
S l University Arkansas MedicalSciences
of for
New York,NY,USA LittleRock, AR, USA
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5. Contents
Dedication ...... .viii 1 3 B i o l o g i c a l , e m i c a l n dN u c l e a r. . . . . . . . . . 1 3 3
Ch a
Tribute .... ..ix Terrorism: Roleof the Laboratory
Listof ontributors.....
C ........xi PhilipM. Tierno MarkS.Lifshitz
lr,
Preface .....xix
Acknowledgements .. ...xxi
tl C l i n i c aC h e m i s t r y
l
I T h eC l i n i c a l a b o r a t o r y
L t-ditr.rl Matthew Pincr"rs PhD,
bv R. MD
M a r kS .I i f s h i t z D
M
Editerd MarkS. t ifshirz
by MD,
M.rllhcr'r, Pincris Phtl,Cre.gorv Threrattc
ll. MD A. Mt) 1 4 E v a f u a t i o n R e n aF u n c t i o n ,
of l ........147
Water,Electrolytes Acid-BaseBalance
and
1 C e n e r aC o n c e p t s a n d A d m i n i s t r a t.i.v . . . . . 3
l .e ManS Oh
Is s u e s
l5 Biochemical arkers f Bone
M o .. . . . . ..170
Anthony Kurec,
S. MarkS Lifshitz
Metabolism
2 OptimizingLaboratoryWorkflow ....12 Katrin Klemm,
M. Michael Klein
I
and Performance
16 Carbohydrates... .......185
Mark 5 Lifshitz, Robert P De Cresce, lrina Lutinger
l. Ruth Weinstock
Mukhtar Khan, S.
3 Pre-Analysis... ....20
17 Lipidsand yslipoproteinemia
D .......200
HerbMiller,
MarkS.Lifshitz
Timothy MarkS.Lifshitz
Hilbert,
4 A n a l y s i s : r i n c i p l eo f I n s t r u m e n t a t i o n. . . . . 3 1
P s .
1 B Evaluation Cardiac
of Injuryand Function. . .219
Robert Sunheimer,
L. Cregory Threatte, S Lifshitz,
A. Mark
lay L.Bock
Matthew Pincus
R
1 9 S p e c i f iP r o t e i n s
c ... ... . .231
5 Analysis:
ClinicalLaboratory
Automation. . . . .56
RichardA. McPherson
Robert Sunheimer,
L. Cregory Threatte
A.
2 0 C l i n i c aE n z y m o l o g y
l .....245
6 Point-of-Care Physician
and Office . . . .64
NaifZ.Abraham Robert Carty, Robert
Jr, P. D. Dufour,
Laboratories
Matthew R. Pincus
Cregory Threatte
A.
2 1 Evaluation LiverFunction
of . ...263
7 P o s t - a n a l y sMse d i c a D e c i s i o n - M a k i n g . . . . . . 6 8
i : l
PhilipM. Tierno D. Robert
Matthew Pincus,
R. Jr, Dufour
Rohan John, MarkS.Lifshitz, Jeffrey Jhang, DanielFink
22 L a b o r a t o r y D i a g n o s i s . . f
.o ....279
B I n t e r p r e t i nL a b o r a t o r ye s u l t s
g R .......76
Castroi ntesti and Pancreatic
nal Disorders
Matthew R Pincus. Naif Z Abraham lr
Martin H. Bluth, Rosemarie Hardin,ScottTenner,
E.
LaboratoryStatistics ......91 Michael E.Zenilman,CregoryA. Threatte
Richard A McPherson
2 3 Toxicology and Therapeutic Drug . . . .297
10 Quality ontrol
C .. ..99 Monitoring
W.CregMiller MatthewR. Pincus,NaifZ. AbrahamJr
1 1 C l i n i c aL a b o r a t o r y I n f o r m a t i c s
l .......112 24 E v a l u a t i o n f E n d o c r i n eF u n c t i o n
o ....326
MarkS.Lifshitz,
CaryE.Blank,
KatherineSchexneider
L Amal F.Farag,
HelenaA Cuber, lamesS.Lo,lamesW.Sharp
1 2 F i n a n c i a l a n a g e m e n.t. . .
M ....122 2 5 R e p r o d u c t i v e u n c t i o na n d P r e g n a n c y. . . . . . 3 6 4
F
MarkL Jaros, MarkS.Lifshitz, Robert De Cresce
P. Robert Webster
A.
6. 2 6 Vitamins TraceElements
and . ..379 40 L a b o r a t o r y A p p r o a c h t o . . . ....770
Martin Salwen
l. ThromboticRisk
Richard Marlar,
A. Louis Fink,
M. lonathan Miller
L.
ltl U r i n ea n d O t h e r B o d yF l u i d s 41 AntithromboticTherapy.... ...778
Louis Fink,
M. lonathan Miller
Richard Mailar,
A. L
E d i t e cb y R i c h a r d . M c P h e r s o n D ,
l A M
Crergory Threatte
A. MD, Matthew R. PincusMD PhD, VI Im m u n o l o g y n d l m m u n o p a t h o l o g y
a
MarkS.Lifshitz D M
Edited H. Davis
by Massey PhD,
MD
2 7 B a s i cE x a m i n a t i o no f U r i n e
. . . .393 Richard McPherson
A. MD
lonathanBen-Ezra,
Shourong
Zhao, Richard McPherson
A.
4 2 O v e r v i e w f t h e l m m u n eS y s t e m
o ....789
2 8 C e r e b r o s p i n a lS y n o v i a l a n d S e r o u s . . . . . . . 4 2 6
, , andlmmunologic isorders D
Body Fluids Richard McPherson, Davis
A. H. Massey
Joseph Knight,Carl R. Kjeldsberg
A.
4 3 fm m u n o a s s a y s d l m m u n o c h e m i s t r y . . . . 7 9 3
an .
YoshihiroAshihara,Yasushi Kasahara. Robert Nakamura
M.
IV Hematology 4 4 L a b o r a t o r y E v a l u a t oo nh e C e l l u l a r. . . . . . . 8 1 9
i ft
lmmune System
E d i t e cb y R o b e r tE . H r - r t c h i s oM D ,
l n
Roger Riley,
S. lonathan Ben-Ezra
Richard . McPherson D
A M
45 LaboratoryEvaluationof ......835
2 9 B a s i c x a m i n a t i o n B l o o da n d B o n e . . . . . . 4 5 7
E of lmmunoglobinFunction and Humoral
Marrow lmmunity
Neerja Vajpayee, Susan Craham,
S. Sylva Bem A. H. Massey
Richard McPherson, Davis
30 H e m a t o p o i e s . s.
i. ......4U 46 Mediators f lnflammation:
o ...U9
SharadMathur, Katherine Schexneider,
Robert Hutchison
E. Complement, Cytokines,
and
AdhesionMolecules
31 ErythrocyticDisorders ...504 H. DavisMassey,
Richard McPherson
A.
M.Tarek
Elghetany,
Katalin
Banki
47 HumanLeukocyte The Major . ... .876
Antigen:
32 L e u k o c y t iD i s o r d e r s
c ....545 Histocompatibility
Complexof Man
Robert Hutchison, Z.Abraham
E. Naif Jr H. Davis Richard McPherson
Massey, A.
33 T h eF l o w C y t o m e t rEcv a l u a t i o n . . . . . . . . . 5 9 9
i of 4 8 T h eM a j o rH i s t o c o m p a t i b i l i t y ........894
Hematopoietic Neoplasia Complexand Disease
BrentL Wood, Michael Borowitz
I lulio C. Delgado, Edmond Yunis
J.
34 lmmunohematology ....618 49 lmmunodeficiencyDisorders ........906
V.
Wendy Beadling,
Laura
Cooling W. Susan Roseff
Kimberly Sandford, D.
35 TransfusionMedicine.... .....670 Evaluation . ... . ..916
50 Cfinicaland Laboratory of
Robertson Davenport, D. Mintz
D. Paul Systemic RheumaticDiseases
36 Hemapheresis ....686 Alberto Miihlen,
Cailos Von Robert Nakamura
M.
leffreyL.Winters,
Alvaro Pineda
A. 51 Vasculitis.... .....933
3 7 T i s s u e a n k i n g n d P r o g e n i t oC e l l s. . . . . . . . 7 1 7
B a r Rex McCallum,
M. David Bylund
I.
Charlene Hubbell,
A. Lazaro Rosales 5 2 O r g a n - S p e c i f i c A u t o i m m u nie e a s e s. . . . . 9 4 5
D s
David Bylund,
J. Robert Nakamura
M.
V H e m o s t a s ia n d T hr o mb o s i s
s 53 Allergic iseases
D ... . .. .961
Henry Homburger
A.
Edited Jonathan Millc.r
by L. MD t,ht)
V l l M e d i c a lM i c r o b i o l o g y
3 8 C o a g u f a t i o n d F i b r i n o l y s.i .
an s .......729
AlvinH. Schmaier, Courtney Thornburg,
D. Steven Pipe
W. Editecl Cail L. WoodsMD,
lry
Richard McPherson
A. MD
39 B f o o dP l a t e l e ta n d V o nW i l l e b r a n d. . . . . . . . 7 4 7
s
Disease 5 4 V i r a lI n f e c t i o n s ...975
lonathan L. Miller. A. Koneti Rao Michael Costello, Margaret
Yungbluth
7. 55 Chlamydial,
Rickettsial,
and . .1000 Diagnosis Hematopoietic. ...1295
7 1 Mofecular of vtl
Mycoplasmalnfections
I Neoplasms
Cail L Woods, David H. Walker David S.Viswanatha, Richard S. Larson
5 6 M e d i c aB a c t e r i o l o g .y. . .
l ....1016 72 MolecularDiagnosis Cenetic
of . . . .1323
CerriS Hall.CailL.Woods Diseases
Wayne Crody,
W. Walter Noll
W.
57 ln Vitro Testing Antimicrobial
of Agents. . . .1048
MichaelB Smith,Cail L Woods 7 3 fdentityAnalysis: of DNA
Use . . . . . .1340
Polymorphisms Parentage
in and
5 8 S p i r o c h e t e n f e c t i o n s. . .
I .... .1059
Forensic Testing
P.RoccoLaSala, MichaelB. Smith
Herbert Polesky,
F. Rhonda Roby
K.
59 M y c o b a c t e r i a . . . . ......1074
Cail L. Woods
60 M y c o t i cD i s e a s e s ......1086
IX C l i n i c a lP a t h o l o g y f C a n c e r
o
PeterC. lwen hrlilt:rl Richarrl Mt l)hcrsorr
bv A. M[),
61 MedicalParasitology ..1119 M.rltlrov i'in<:us l'jhD.
[(. MI) Martin I]luth
H. MI) l'hl)
Thomas R Fritsche, RangarajSelvarangan
74 D i a g n o s i s a n d M a n a g e m e n t o f .....1353
62 MolecularPathology Infectious
of ..1169 CancerUsingSerologic TumorMarkers
Diseases
Peng Lee,Matthew R. Pincus, RichardA. McPherson
Michael A. Pfaller
75 Oncoproteins Tumor
and Early . . . . .1367
6 3 S p e c i m e C o l l e c t i oa n d
n n ...1188 Detection
H a n d l i n go r D i a g n o s io f I n f e c t i o u D i s e a s e s
f s s Matthew R Pincus, Paul W. Brandt-Rauf,Martin H Bluth
AnnC Croft, CailL.Woods
76 Diagnosticand Prognostic
lmpactof . . . . . .1381
6 4 B i o t e r r o r i s m :i c r o b i o l o g y
M ...1204 H igh-Th
roughputGenom ic and Proteomic
ludvA Dalv Technologies the Post-Cenomic
in Era
JenniferBeane,Aran Kadar,Charles DeLisi,Martin H. Bluth
Avrum Spira
V l l l M o l e c u l a rP a t h o l o g y
I r l i l c r l r v l l i z . r l r c { l / n q < 'rr , 1 1,)l r l )
r l
r V l , r l l l r clrl r ;I ) i r t L t s . 4 ll)' h [ )
" r N APPEN D ICES
lrriitt:ri Naif1 rlrrrlranr MIf Plril
hv Jr
6 5 f n t r o d u c t i o no M o l e c u l a r
t . ...1225
Pathology 1 P h y s i o l o g i c S o l u t i o nu f,f e r s ,
B s ......1395
Matthew R Pincus, Elizabeth R. Unger
Acid-Base Indicators,
66 M o f e c u l a D i a g n o s t i c B:a s i c
r s . .. . ...1228 Standard Reference Materials,
P r i n c i p l ea n dT e c h n i q u e s
s and Tem peratu Conversions
re
MartinSteinau,
Margaret Piper,
A Elizabeth
I_.lnger 2 D e s i r a b l e W e i g hB s ,d y S u r f a c.e . . . . . . . . 1 3 9 8
to .
Area,and BodyMassIndex(BMl)
67 P o l y m e r a s eC h a i n R e a c t i o n .. .1239
3 A p p r o x i m a t i o n s o f T oB ao o d
tl l ......1402
and Other Chain Reaction molification
A
Volume(TBV)
Technology
4 PeriodicTableof the Elements. . . . . .1403
Frederick5 No/te, CharlesE Hill
5 SlUnits . ..1404
68 H y b r i d i z a t i o n r r a y T e c h n o l o g i e . . . . . . . . . 1 2 5 0
A s H. Peter
Lehmann
Martin H Bluth,MichaelE.Zenilman JohnBernardHenry
69 A p p l i c a t i o n so f C y t o g e n e t i c s . .. . ...1260 6 C o m m o n C h i m e r i cC e n e s l d e n t i f i e d . . . . . . 1 4 1 9
in Modern Pathology in Human Malignancies
Constance
Stein NaifZ Abraham Jr
70 Establishing olecular
aM . . .. .1283
Diagnostics
Laboratory lndex .. . .1422
Andrea Ferreira-Conzalez,David S. Wilkinson,
Carleton T. Carrett
8. Dedication
To
our wlves,
StephanieSammartinoMcPherson
and Naomi Pincus
and children,
lennifer and MarianneMcPherson
for their love and support in the undertakingof this work for which we aredeeplygrateful.
9. Dr John BernardHenry: A Tribute
Hentl"s Clinical Diagnosisarul Management by LaboratoryMethods is a highly synthesisand the broad coverageof the vast area encompassing the 6eld of
acclaimed text in the field of clinical pathologyand has served as a major clinical pathology ensured that this book succeeded in serving as the
resource for practitioners in all fields of medicine It has chronicled the standard referencetext for both laboratorians and clinicians
dramatic and revolutionary changes in diagnostic medicine for almost a Both Drs Davidsohn and Henry edited the 15th edition of this book,
century It was first written under the title A Manual ol Clinicnl Diagnosisin published n 7974 Dr Davidsohn died in 1979 at the age of 84, and Dr
1908 by the legendaryJamesC Todd MD, who edited the 6rst six editions, tienry became the editor for the 16th-20th editions In the 16th edition,
and was joined on the sixth edition by Dr Arthur H Sanford MD Dr Sanford reflecting his emphasis on patient care and the emerging importance of
continued with four more editions of this book on his own and was ioined using laboratory tests to follow the progression ofdisease and the efficacy
on the 11th edition by Dr George G Stillwell and on the 12th edition by Dr of therapy, Dr Henry gavethis book its current title, Clinical Diagnosis and
Benlamin B Wells The 13th edition was edited by Dr Wells and Dr Israel Management by Laboratory Methods Under his guidance, this textbook
Davidsohn, a pioneer in the field of clinical and diagnostic immunology, has continued to maintain and expand its tradition of informing the
and was renamed Clinical Diagnosis by LaboratoryMethods This changein reader of the most recent develoPments in laboratory testing for the
title reflected the major shift in medical diagnostic testing from disparate diagnosis and treatment of diseasesand of describing how testing is used
laboratories, many using indigenous methodologies, to the central both to screen for the presenceof diseaseand to monitor progress in the
diagnostic laboratories using standardized testing with appropriate management of disease.
method verification. It is a great honor for both of us that we have inherited the mantle of so
ln 1969, Dr John Bernard Henry joined Dr Davidsohn in the editorship prolific and distinguished a medical scholar as Dr Iohn Bernard Henry
of the 14th edition of this textbook This was a most fortunate Both of us have benefited immensely from our close association with him
development Dr Henry as Professor of Pathology at the State University over the past several decades It is with great humility and respectthat we
of New York Upstate Medical Center in Syracuse and Director of the assume editorship of this flagship textbook that has been molded by him
Clinical Pathology service at this medical center, was a pioneer in the and by all of the other outstanding leaders in the field of diagnostic
organization of the clinical pathology laboratories and an innovator in medicine We feel most fortunate to be able to continue to interact with Dr
introducing state-of-the-an methods into the centralized diagnostic Henry We are and will always be deeply indebted to him for his massive
laboratory Dr Henry has been and continues to be an outstanding teacher contributions to the fields of clinical pathology and diagnostic medicine,
who has been central to the training of multiple generationsof leadersin the his outstanding example as a physician and teacher, and his profound
field of laboratory medicine His ma jor focus has alwaysbeen on the patient, contributions as editor of this textbook that have ensured that this book
and he establishedthe principle that the ultimate verification ofthe validity has taken its place among the most significant textbook contributions in
of the result of any test is whether it leads to appropriate and effective modern medicine.
therapeutic intervention This principle requires close interactions betlveen In tribute to him and his leadership over the last seven editions ofthis
the clinical pathologist and the clinician Thus, as an editor of this book, it will henceforth be permanently titled Henry's Clinical Diagnosis
textbook, in addition to promoting discussions of the exciting new and Managementby Laboratory Methods.
developments in testing methodologies that span a vast panorama from
spectrophotometry to microscopic diagnosis to molecular biological
approachessuch as polymerase chain reaction, Dr Henry also emphasized Richard A. McPherson MD
the clinical aspects of the diseases that are diagnosed by them This Matthew R Pincus MD PhD
10.
11. Listof Contributors
'",r
N a i fZ . A b r a h a m r , ; l r
J " G a r yE .B l a n k! ' i : i :
Staff Pathologist, Director of Chemistry Associate Professor Clinical Chemistry
of
H ematology, Immunology, and Microbiology, Department Department Pathology
of
of Pathology,VeteransAffairs Medical Center U niversityof Pittsburgh
Assistant Professor,Upstate Medical University PA,
Pittsburgh, USA
Syracuse,NY, USA
Martin H. Bluth '.:;, ,':ili
Directorof Research
Yos hih i r o h i h a r a
As Professor
Assistant
Vice President, Board Member Departments Surgery
of and Pathology
Research Development Division
& SUNYDownstate MedicalCenter
Fujirebio Inc. Brooklyn,NY USA
Tokyo, fapan
Jay L. Bock r,iil i'i:i-i
K a t a l i n a n k i' ' '
B Professor ActingChair
and
Department Pathology
of
Assistant Professorof Pathology
StateUniversityof New York at StonyBrook
Director of Special Hematology
Department of Pathology
StonyBrook,NY,USA
SUNY Upstate Medical University ':, t:);:!.i
Michaef J.Borowitz'
Syracuse,NY, USA Professor Pathology
of
Department Pathology
of
WendyV.B e a d l i n g .' fohns Hopkins University/Medical Center
Assistant Supervisor,Blood Bank Baltimore,MD, USA
Clinical Pathology PaulW Br andt- Rauf r g]il[' r $]t- ]irIt
'
SUNY Upstate Medical University Chairman
Syracuse, NY USA Department of Environmental Health Sciences
Mailman School of Public Health
Je n n ife r a n e
Be Columbia College of Physiciansand Surgeons
PhD Candidate NewYork, NY, USA
Bioinformatics Program
Boston University
DavidJ. Bylund
Staff Pathologist
Boston, MA, USA
Department of Pathology
Scripps Clinic - Torrey Pines
Sylva em':,i.'
B La lolla, CA, USA
Clinical Assistant Professor
Department of Pathology RobertP.Carty ilir[]
Division of Hematopathology Professor
Associate
SUNY Upstate Medical University Department Biochemistry
of
Syracuse,NY, USA SUNYHealthScience Centerat Brooklyn
Brooklyn,NY USA
Jonathan en-Ezra
B Laura ooling
C
Professorof Pathology Clinical Assistant Professor
Department of Pathology AssociateDirector, Transfusion Medicine
Virginia Commonwealth University School of Department of Pathology
Medicine University of Michigan Hospitals
Richmond, VA, USA Ann Arbor, MI, USA
12. Mich a e lC o s t el l o['h l ) Andrea Ferreira-Gonzalez [,.]
llh
Technical Director Professorand Director
Advocate Shared ServicesLaboratory Molecular Diagnostics Laboratory
Advocate Lutheran General Hospital Department of Pathology
Park Ridge IL, USA Medical College of Virginia
Virginia Commonwealth University
(A5("t,)
Ann C. Croft N.,tI Richmond, VA, USA
Supewisor
BacteriologyLaboratory
Daniel Fink ,ttl:
AssociateClinical Professorof Pathology
ARUPLaboratories
Department of Pathology
Salt LakeCity, UI, USA
Columbia University Medical Center
NewYork, NY, USA
J u d yA. D a l y i r li t)
Clinical Professor LouisM . Fink,4t]
Departmentof Pathology Director, Core Laboratory Services
Universityof Utah Schoolof Medicine Nevada Cancer Institute
Salt LakeCiry UT, USA Las Vegas,NV, USA
RobertsonD. Davenport,,1D ThomasR. FritschePhlJ Mtl A8tu'1,4
Associate Professor of Pathology Director of Laboratories
Medical Directot Blood Bank and Transfusion Service JMI Laboratories
Ann Arbor, MI, USA North Liberry, IA, USA
CarletonT. Carrett Mn [j'h["]
Robert P.De Cresce,,41]
MffiAe46?Fl Division Chief
Chairman,Department Pathology
of Pathology
Director,RushMedicalLaboratories Virginia Commonwealth University
RushUniversityMedical Center Richmond,VA, USA
Chicago,IL, USA
Susan Gr aham&4S
S. N4T( ASCP) SH
Associate
Professorand Chair
J u l i oC . D e l g a d oMt)
AssistantProfessor Pathology
of Departmentof Clinical LaboratoryScience
University of Utah; SUNYUpstateMedical University
AssociateDirectot Laboratory Immunology
of Syracuse, USA
NY,
ARUPLaboratories Wayne Crody,'tU []hil]
Salt LakeCity, Ln, USA Professor,Division of Molecular Pathology and Medical
Genetics
Ch a r l e s e L i s iP h l l
D Director, Diagnostic Molecular Pathology Laboratory
Professol Senior AssociateProvost Departments of Pathology & Laboratory Medicine,
Curriculum & Teaching Pediatrics, and Human Genetics
Boston University UCLA School of Medicine
Boston, MA, USA Los Angeles, CA" USA
D. RobertDufour Mi) HelenaA. Guber tu'tll
Chief, Pathologyand LaboratoryMedicine Service Professor Medicine
Assistant of
VeteranAffairs Medical Center Department Endocrinology
of
Washington, DC, USA New York Harbour HealthcareSystem
Brooklyn, NY, USA
M. Tarek Elghetany,[t[] Ger aldine Hall t' hi)
S.
Professor Vice-Chairman
and
Professor of Pathology
Departmentof Pathology
DMsion of Pathology and Laboratory Medicine
University of Texas
Medical Branch
Cleveland Clinic Foundation
Calveston, TX, USA
Cleveland, OH, USA
Amal F.Farag,!tD Rosemarie Hardin N.'ti)
E.
AssistantProfessor Medicine
of Resident
Department Endocrinology
of Departmentof Surgery
New York Harbour HealthcareSystem SUNY DownstateMedical Center
Brooklyn, NY, USA Brooklyn, NY, USA
13. J o h nB e r n a r d e n r y
H Aran Kadal ,iJ
Distinguished ServiceProfessorof Pathology PGY4l4thYear Resident
SUNY Upstate Medical University The Pulmonary Center
Syracuse,NY, USA Boston University Medical Center
Boston, MA, USA
T i m o t h yH i l b e r t
Assistant Professorof Pathology Kasahar i' lr
Yasushi a
New York University School of Medicine Visiting Professor
New York, NY USA Department of Clinical Pathology
School of Medicine
C h a r l e s .H i l l
E Showa University
Assistant Professor Tokyo, Iapan
Department of Pathology and Laboratory Medicine
Emory University School of Medicine Mukhtar l. Khan 'r'1i.i
Atlanta, CA, USA Assistant Professorof Medicine
Department of Endocrinology, Diabetes, and Metabolism
H e n r yA . H o m b u r g e r SUNY Upstate Medical University
Professorof Laboratory Medicine Syracuse, NY USA
Mayo Clinic College of Medicine
Consultant Car l R. Kjeldsber g
Mayo Clinic Professor Pathology
of
Rochester,MN, USA University of Utah School of Medicine
CEO and Chair, Board of Directors
C h a r f e n e AH u b b e l lr , '
. , . : : . i.' ; ARUP Laboratories
Adjunct AssociateProfessor,Clinical Laboratory Science Salt Lake Ciry, UT, USA
College of Health Professions
Supervisoq, Histocompatibility, Immunogenetics and
M i c h a e J .K l e i n
l
Professorof Pathology
Progenitor Cell Bank
Head, Section of Surgical Pathology;
State University of New York, Upstate Medical University
Senior Scientist,Center for Metabolic Bone Disease
Syracuse, NY USA
The University of Alabama School of Medicine
Rober tE.H u t c h i so n Birmingham, AL, USA
Professorof Pathology, Director of Hematopathology and
Katrin . Klemm
M
Director of Clinical Pathology
AssistantProfessor
SUNY Health ScienceCenter
Department of Pathology
Syracuse, NY USA
University of Alabama
Pet erC . l w e n Birmingham, AL, USA
AssociateProfessor
Pathology and Microbiology
Joseph Knight:i::
A.
Professor Pathology
of
University of Nebraska Medical Center
Department of Pathology
Omaha, NE, USA
University of Utah School of Medicine
M a r k L .J a r o s Salt Lake City, UT, USA
Administrative Director A n t h o n y S . K u r e c r ' . ' i lir.rl i l r i i * 5 { , i r l
Department of Pathology/Rush Medical Laboratories Administrator, University Pathologists Laboratories,LLP
Rush University Medical Center Clinical AssociateProfessor
AssociateProfessor,College of Allied Health SUNY Upstate Medical University
Rush University Syracuse, NY USA
Chicago, IL, USA
R i c h a r d5 . L a r s o n1 : i i f i r l ]
JeffreyJhang Senior AssociateDean for Research,
Assistant Professorof Clinical Pathology AssociateProfessorof Pathology
Depanment of Pathology Department of Pathology
Columbia University Medical Center University of New Mexico HSC
NewYork, NY USA Albuquerque, NM, USA
Rohan ohn
J P.Rocco LaSala
Resident Fellow, Medical Microbiology
Department of Pathology Department of Pathology
Rush University Medical Center University of TexasMedical Branch
Chicago, IL, USA Galveston.TX, USA
14. x i v P e n gL e e , i i i i j ' i : i , r Richard McPherson
A. i'41)
AssistantProfessor Harry P. Dalton Professorand Chairman
Department Pathology
of Division of Clinical Pathology
New York UniversityMedicalCenter Virginia Commonwealth University;
Staff Pathologist Director
New York Harbor VA Medical Center Clinical Pathology
Brooklyn and New York, NY, USA Medical College of Virginia Hospitals
H. Pe t e rL e h m a n n i l S Richmond, VA, USA
E
Professor,Department of Pathology
Louisiana State Universiw Medical Center
W . Gr egM iller tr hiS
Professorof Pathology
New Orleans, tA, USA
Department of Pathology
Ma r k S. L i f s h i tz { j
rl Virginia Commonwealth University
Director, Clinical Laboratories Richmond, VA, USA
NYLI Medical Center
Clinical Professor,Department of Pathology Her b M iller Plr l];tl-iA5{ - f} )
New York University School of Medicine {.t5 iH{-;i
NewYork, NY, USA Chairman and Director
* , 1 [ i , 1 b { - i ' }i l i r l - } 1 . t , i } q - " { , Department of Clinical Laboratory Sciences
James S. Lo
Director,PulmonaryFunctionBlood GasLaboratory College of Health Sciences
and
Rush University
Assistant Laboratory
Director,Department Pathology Chicago,IL, USA
of Vassar Brothers Medical
Center
Affiliate Professor MedicalTechnology,Departmentof
of JonathanL. Miller ;4* Fli"rl)
Professorand Vice Chairman
MedicalLaboratory Sciences
Department of Pathology
MaristCollege
The University of Chicago
Poughkeepsie, USR
NY
Chicago,IL, USA
l r i n a L u t i n g e r l r 1 *2 i ! . p 2 , 1 1 i . . r r 5 i . l - i
,
Senior Administrative Director PaulD. M intz 11]
Clinical Laboratories Professor,Departments of Pathology and Internal
TischHospital,Labs Medicine
NYLI Medical Center Director Division of Clinical Pathology/Clinical
NewYork,NY,USA Laboratories
University of Virginia Health System
Richard A. Marlar ili:i]
Charlottesville, VA, USA
Professor Pathology
of
Associate
Director,Coagulation and Special
Coagulation
RobertM. Nakamura,.'tD
Laboratories
Senior Consultant and Chairman Emeritus
VeteranAffairs Medical Center;
Department of Pathology
OklahomaCity, OK, USA
Scripps Clinic
H. DavisMasseytutl] llhilt La Jolla, CA, USA
AssistantProfessor Pathology
of
Virginia Commonwealth University Walter W. Noll lti]
Richmond,VA USA Professorof Pathology
Department of Pathology
S h a r a d a t h u r 4 []
M
Dartmouth-Hitchcock Medical Center
AssistantProfessor
Lebanon, NH, USA
Departmentof Pathologyand LaboratoryMedicine
University of Kansas
Medical Center;
Frederick Nolte lihil
S.
Chief Pathology and LaboratoryMedicine Service
Professor,Pathologyand LaboratoryMedicine
VA MedicalCenter
Emory University Schoolof Medicine
Kansas City, MO, USA
Atlanta, CA, USA
RexM. McCallumtuii]
Clinical Professorof Medicine Division of Rheumatology M an S.Oh ,tL]
Associate Medical Director of the Private Diagnostic Clinic Professorof Medicine
Senior Clinical Advisor, Duke Department of Medicine Department of Medicine
Duke University School of Medicine State University of New York
Durham, NC, USA Brooklyn, NY, USA
15. MichaelA.Pfaller', j &,41)
LazaroRosales
Professorand Director, Molecular Epidemiology and AssociateProfessorof Pathology
Fungus Testing Laboratory Director of Hemapheresis and Deputy Director of
Departments of Pathology and Epidemiology Transfusion Medicine
University of Iowa College of Medicine and College of Department of Pathology
Public Heath Upstate Medical University
Iowa Ciry IA, USA Syracuse,NY USA
SusanD. Roseff
M a t t h e wR . P i n c u s. . , , , , 1 "'ri?
Medical Director, Transfusion Medicine
Professor,Department of Pathology Virginia Commonwealth University Medical Center
State University of New York Health SciencesCenter at AssociateProfessor
Brooklyn; Department of Pathology
Chairman, Department of Pathology and Laboratory Virginia Commonwealth University School of Medicine
Medicine Richmond, VA, USA
New York Harbor VeteransAffairs Health Care System
Brooklyn and New York, NY USA Martin l. Salwen:v:f
.:
Distinguished ServiceProfessor
Alv a roA . Pi n e d a' ,, '
Department of Pathology
State University of New York
Emeritus Professorof Laboratory Medicine
Brooklyn, NY USA
Mayo Clinic College of Medicine
Rochester,MN, USA Kimberly W. Sanford l'l|) ,r"1iir{"i}:
F
Chief Resident
St ev en . P i p e . : : :
W Department of Pathology
AssociateProfessor Virginia Commonwealth University School of Medicine
Department of Pediatrics Richmond, VA, USA
University of Michigan K a t h e r i n el . S c h e x n e i 6 l st , 1 i " ]
l
Ann Arbor. ML USA Medical Director, Blood Bank
Naval Medical Center Portsmouth
Ma rg a r e A. Pi p e r
t PortSMOUth,VA, USA
Senior Consultant Alvin H. Schmaier,iiii
Technology Evaluation Center
Professorof Internal Medicine and Pathology
Blue Cross Blue Shield Association
Directot Coagulation Laboratory
Atlanta, CA, USA Department of Internal Medicine and Pathology
University of Michigan
H e r b e r tF .P o l e s k y " , ,
. Ann Arbor, MI, USA
Former Professorof Laboratory Medicine and Pathology
University of Minnesota School of Medicine
Rangaraj it't lll:t)
Selvarangan
Assistant Professorof Pediatrics
Minneapolis, MN, USA
University of Missouri School of Medicine;
Director of Clinical Microbiology and Virology
A . Kon e t iR a o " ,'. Laboratories
Professorof Medicine, Thrombosis Researchand
Children's Mercy Hospital
Pharmacology
Kansas City, MO, USA
Assistant Dean, MD PhD Program
Division of Hematology and Thromboembolic Diseases ames
.f J'''{11
Sharp ttU"1.
Temple University School of Medicine Director of Laboratories
Philadelphia,PA, USA Department of Pathology
VassarBrothers Medical Center
R o g e rS . R i l e y ' , . r i i! ] i r i " l Medical Directot Medical Technology Program
Director of Coagulation and Professorof Pathology Department of Medical Laboratory Sciences
Department of Pathology Marist College
Virginia Commonwealth University Poughkeepsie, NY, USA
Richmond, VA, USA Michael B. Smith ,r.'r!.:
Assistant Professorand Director
R h o n d a K . R o b y : .r : i : i
. Division of Clinical Microbiology
SeniorForensic Specialist Department of Pathology
Applied Biosystems University of Texas Medical Branch
FosterCity, CA, USA Galveston, TX, USA
16. A v r u m S p i r a tl ) David S.Viswanatha&.4$FKCf){;
Assistant
Professor Senior AssociateConsultant
MED PulmonaryCenter Division of Hematopathology Mayo Clinic;
BostonUniversity AssociateProfessor
Boston,MA, USA Mayo Clinic College of Medicine
Rochester,MN, USA
Constance Stein$)1r6.]
K.
Associate
Professor
Department Pathology
of
CarlosAlberto von Mtihlen tutl] Fht]
Full Professor Rheumatologyand Internal Medicine
of
UpstateMedicalUniversity
PontificalCatholicUniversitySchoolof Medicine
SyracusgNY, USA
Porto Alegre,RS,Brazil
Ma r t i n St e i n a u )frl l
l
Division of Viral and Rickettsial Diseases David H. Walker to4["]
National Center for Infectious Diseases Professorand Chairman
Atlanta, GA, USA Department of Pathology
University of Texas Medical Branch
Ro b e r tL . Su n h e i me r{$tu l I (A q (.p iSC gls
r Calveston, TX, USA
AssociateProfessor
Department of Clinical Laboratory Science
Robert A. Webster flh [-]
SUNY Upstate Medical University
AssistantProfessor
Syracuse,NY, USA
Departments Pathology,
of Biochemistryand Clinical
Sco t t T e n n e tD N l P l l F A C P C C
r IA LaboratoryScience
Division of Castroenterology,Maimonides Medical Center Associate Directot RushMedicalLaboratories
AssistantProfessorof Medicine, Mount Sinai School of Directot CoreLaboratory
Medicine RushUniversity Medical Center
Director, Medical Education and Research Chicago, USA
IL,
BrooklynGl.com
Brooklyn, NY, USA RuthS.Weinstock Phlf,
tu4D
Professorof Medicine and Chief, Endocrinology, Diabetes
CourtneyD. Thornburgh4[) and Metabolism
Lecturer,
Department Pediatrics Communicable
of and Department of Medicine
Diseases SUNY Upstate Medical University
Universityof Michigan Syracuse,NY, USA
Ann Arbor, MI, USA
GregoryA. Threatte ,.1* DavidS.W ilkinsonM D Phil
Professorand Chairman Professorand Chair
Department of Pathology Department of Pathology
SUNY Upstate Medical University Virginia Commonwealth University
Syracuse,NY, USA Richmond. VA, USA
P h i l i p . T i e r n oJ r P h D
M JeffreyL. Winters MD
Directot Clinical Microbiology and Immunology Professor Laboratory
Assistant of Medicine
AssociateProfessot Departments of Microbiology and Department Transfusion
of Medicine
Pathology Mayo Clinic Collegeof Medicine
New York University Medical Center Rochester, USA
MN,
NewYork, NY, USA
Elizabeth
Unger,,ttlPiiil Brent L.Wood ,tD Pht)
TeamLeader AssociateProfessorof Laboratory Medicine
Human Papillomavirus Department of Laboratory Medicine
Laboratory
National Centerfor InfectiousDiseases University of Washington
Atlanta, GA"USA Seattle,WA, USA
NeerjaVajpayeeMD Gail L.Woods ,!iD
Clinical Assistant Professor Director, Clinical Laboratories
Department of Pathology Professorof Pathology
Division of Hematopathology Department of Pathology
SUNY Upstate Medical University University of Arkansasfor Medical Sciences
Syracuse,NY, USA Little Rock, AR, USA
17. Margaret
Yungbluth
MD MichaelE.ZenilmanMD
Staff Pathologist Clarenceand Mary Dennis Professor
and Chairman
Departmentof Pathology Departmentof Surgery
St FrancisHospital SUNYDownstateMedical Center
Evanston,IL, USA Brooklyn, NY, USA
Edmond Yunis
J. MD ShourongZhao MD MS
Professor Pathology
of Fellowof Hematopathology
HarvardMedicalSchool Departmentof Pathology
Boston,MA, USA Vi rginia Commonwealth University Health System
Richmond,VA, USA
18.
19. XIX
Preface
'fhe
role of clinical pathology and laboratory medicine conrinues to grow as servicesand the growth of new technologies to support them is the subject
the single largestcomponent of objective scientific data within the medical of Ch 6 The post-analysis processes of reponing, medical decision-
'Ihe
record of patients. ever-increasing ease with which conventional making, and interpretation of results are crucial to the utility of laboratory
laboratory anallses can be provided and the broadening diversity of lesting (Ch 7) Seleaion and interpretation of laboratory information and
measurements with esoteric assayscontribute to clinical management from results to achieve the most cost-effective and efficient medical problem
prenatal days to newbom screening through childhood, adulthood, and into solving with clinical laboratory testing is explored in Ch. 8 Statistical analysis
geriatric ages.This lifeJong trail of medical observations and laboratory test (Ch 9) is immensely imponant to all phases of monitoring laboratory
results is now being organized into a continuous and contemporaneous processesand decision making with some of its most explicit applications in
electronic medical record The challenge for fi,rture medicine lies in how best the area of quality control (Ch. 10). The multitude of laboratory results and
to use all of this information to provide counseling to patients about their reponing can only be managed by sophisticated information systems
behavior modifications and disease risk amelioration based on a wide that are an essential pan of any clinical laboratory (Ch. tt) and that are
range of medical data with an expanding core of generic resring, in becoming more important as the tools by which integration of clinical
addition to traditional measures of organ function and metabolism information at multiple levels can be made available to the physician
revealed through chemical, hematological, microbiological, and other client The choice of instrumentation, clinical laboratory automation, and
l a b o r a t o r yd i s c i p l i n e s computer systems in a laboratory largely determine its productivity
The expansion in knowledge of the human genome and its conversion (increased volume and variety of complex measurements/examinations) and
into proteomic phenotypes of the human body present a range of selection of the most expeditious laboratory service responsive to providers'
opportunities for exploring health and diseaseas never before practiced and patients'needsin terms ofaccess, cost, and quality. The financial impact
The methods of examination both for nucleic acids and protein expression and solutions to challenges for pathologists and all laboratorians from
of genes will surely transform the way that laboratories provide clinical managed care with capitated reimbursements and/or discounted service
diagnostic servicesfor decadesto come Numerous applications to clinical contracts are paramount to the survival of both the laboratories
testing have already come to fruition in microbiology, coagulation, tissue themselves and to the institutions they serve (Ch 12) A relatively new
typing genetic diseases,cancer and hematologic malignancies. The environ- challenge facing laboratories is preparednessand appropriate responsesto
ment provided by clinical laboratories rhat demands rigor in analysis, quality threats of bioterrorism on local, regional, and national levels (Ch 13)
control, professional competencies, and cost-effective operations will also These themes run through all 76 current, new updated and/or augmented,
foster the application of this new knowledge and these new methods into strengthened chapters that embrace each topic in a compelling manner
accepted standard of practice. We should expect lhat the most successfirl from patient specimen collection and processing to the reporting of
future practitioners of laboratory medicine will be those well versed in and results
prepared to pursue advances in informatics, basic analytic methods, Part II, Clinical Chemistry is now organized systematically to present
communications with clinical colleagues, and participation in national and laboratory examinations according to the diseases of organ systems It
international efforts to standardize and implement complex changes in begins with the evaluation of renal function, water, electrolytes,metabolic
our profession. It is at multiple levels of society that the laboratory can intermediates and molecules of nitrogen exchangg and acid-basebalance,
serve from individual patient testing through public health initiatives for that are so important in monitoring patients for critical care as well as in
diseaseprevention, and extending to industry and government policies for the management of parients with kidney and pulmonary disorders (Ch 14)
health care and its reform to support best practices and promote health -lhis
subject leads into the increasingly important laboratory evaluation of
and well being in a climate of limited financial resources bone metabolism and bone loss (Ch 15) Ever stronger emphasis is now
The 21"' edition of this book comes at nearly the century mark since its placed on carbohydrates in the laboratory diagnosis and management of
inception with its first publication in i908 lt has remained throughout diabetes mellitus and other disorders (Ch 16) Ch 17 is a new pre-
that time as the authoritative source of information for residents,students, sentation on studies of lipids and their abnormalities that are so irnportant
and other trainees in the discipline of clinical pathology and laboratory in cardiovascular disease risk assessment, while Ch 18 deals with the
medicine and for physicians and laboratorians in that practice The 21.1 immediate evaluation of heart diseaseand cardiac injury The role of specific
edition incorporates new discoveries and applications in all chapters to proteins of the blood and electrophoretic intelpretations are emphasized in
fulfill its mission of being a comprehensive textbook thar is up-to-date and Ch 19, while clinical enzymology is covered in Ch 20. Assessmentof liver
readable Most notable in the format of this edition is the use of color function is presented in Ch 21 and that of gastrointestinal and pancreatic
throughout the book with inclusion of many more images and graphical disorders in Ch 22 Toxicological anal)'sis and therapeutic drug monitoring
figures than before One of our goals has been to presenr laboratory are discussed in Ch. 23 with the complementary methods of evaluating
findings in a rendition as close as possible to actual practice as endocrine function in Ch 24 Ch 25, on reproductive and pregnanry
encountered in the real-life conditions of working at the bench. This testing, and Ch 26, on vitamins and trace metals, complete Part II.
approach has allowed each author the opportuniry to incorporate figures Part III, Urine and Other Body Fluids, covers basic examination of urine
that illustrate diagnostic principles and interpretations. (Ch 27) A special area of consideration is analysis of body fluids such as
Part I, The Clinical Laboratory deals with the organization, purposes, cerebrospinal fluid, synovial fluid, and serous fluid (Ch 28).
and practices of analysis, interpretation, and management within the Pan IV Flematology, updates the examination of blood and bone
clinical laboratory Overall, we have reorganized this section, for the sake marrow (Ch 29), hematopoiesis (Ch 30), and erythrocytic (Ch. 31) and
of clariry by considering, in order, pre-analytical, analytical and leukocytic (Ch 32) disorders. The rapidly growing area of flow cytometric
post-analytical aspects of laboratory testing Specifically, issues of analysis in hernatology is emphasized (Ch. 33). Immunohematology (Ch.
administrative organization and operations are discussedin Chs 1 and 2. 34) and transfusion medicine (Ch. 35) addresspre-transfusion testing and
The approach to proper specimen collection, transport, and handling and problem-solving of untoward or unexpected reactions as well as therapy
other pre-anal)'ticalvariables are described in Ch. 3 Principles ofanalysis, with blood products (components and derivatives). Chs 36 and 37 cover
instrumentation, and automation are covered in Chs 4 and 5. Extension of therapeutic applications of apheresisincluding collection, processing and
laboratory servicesbeyond that of a central laboratory in a hospital to the dispensing progenitor/stem cells from bone marrow, peripheral blood,
arena of outpatients along with the regulations covering those near-patient and cord blood coupled with tissue banking.