Accurate results in the clinical laboratory a guide to error detection and correction

ACCURATE RESULTS IN THE CLINICAL LABORATORY A Guide to Error Detection and Correction SECOND EDITION Edited by AMITAVA DASGUPTA, PHD, DABCC Professor of Pathology and Laboratory Medicine University of Texas McGovern Medical School Houston, TX, United States JORGE L SEPULVEDA, MD, PHD Professor of Pathology and Cell Biology Columbia University Vagelos College of Physicians and Surgeons New York, NY, United States List of contributors Susan J Hsiao, MD, PhD Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United States Amid Abdullah, MD University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada Maria P Alfaro, PhD Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, United States Chris Altomare, BS United States Laura M Jacobsen, MD Department of Pediatrics, Division of Endocrinology, University of Florida, College of Medicine, Gainesville, FL, United States DRUGSCAN Inc., Horsham, PA, Kamisha L Johnson-Davis, PhD Department of Pathology, University of Utah School of Medicine, ARUP Laboratories, Salt Lake City, UT, United States Leland Baskin, MD University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada Steven C Kazmierczak, PhD Department of Pathology, Oregon Health & Science University, Portland, OR, United States Lindsay A.L Bazydlo, PhD Department of Pathology, University of Virginia, Charlottesville, VA, United States Jessica M Boyd, PhD Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Calgary Laboratory Services, Calgary, AB, Canada Elaine Lyon, PhD Clinical Services Laboratory, HudsonAlpha Institute for Biotechnology, Huntsville, AL, United States Larry A Broussard, PhD Department of Clinical Laboratory Sciences, Louisiana State University Health Sciences Center, New Orleans, LA, United States Gwendolyn A McMillin, PhD Department of Pathology, University of Utah School of Medicine, ARUP Laboratories, Salt Lake City, UT, United States Violeta Cha´vez, PhD Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX, United States Christopher Naugler, MD University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada Elena G Nedelcu, MD Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States Alex Chin, PhD University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada Andy Nguyen, MD Department of Pathology and Laboratory Medicine, University of Texas McGovern Medical School, Houston, TX, United States Anthony G Costantino, PhD DRUGSCAN Inc., Horsham, PA, United States Amitava Dasgupta, PhD, DABCC Department of Pathology and Laboratory Medicine, University of Texas McGovern Medical School, Houston, TX, United States Octavia M Peck Palmer, PhD Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States; Department of Clinical and Translational Science, University of Pittsburgh School, Pittsburgh, PA, United States Pradip Datta, PhD Siemens Healthineers, Newark, DE, United States Robert A DeSimone, MD Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, United States Amy L Pyle-Eilola, PhD Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, United States Uttam Garg, PhD Department of Pathology and Laboratory Medicine, Children’s Mercy Hospitals and Clinics, The University of Missouri School of Medicine, Kansas City, MO, United States S.M Hossein Sadrzadeh, PhD Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Calgary Laboratory Services, Calgary, AB, Canada Neil S Harris, MD Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville, FL, United States Jorge L Sepulveda, MD, PhD Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States Joshua Hayden, PhD Department of Pathology and Laboratory Medicine, Weill Cornell Medical Center, New York, NY, United States xi xii LIST OF CONTRIBUTORS Brian Rudolph Shy, MD, PhD Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States George Vlad, PhD Department of Pathology & Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY, United States Aaron Stella, PhD University of Massachusetts Lowell, Lowell, MA, United States Amer Wahed, MD Department of Pathology and Laboratory Medicine, University of Texas McGovern Medical School, Houston, TX, United States Yvette C Tanhehco, PhD Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York-Presbyterian Hospital, New York, NY, United States Ashok Tholpady, MD Department of Pathology and Laboratory Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, United States William E Winter, MD Department of Pediatrics, Division of Endocrinology, University of Florida, College of Medicine, Gainesville, FL, United States; Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville, FL, United States Christina Trambas, MD, PhD Chemical Pathologist, Chemical Pathology Department, Melbourne Pathology, Collingwood, VIC, Australia Alison Woodworth, PhD Pathology and Laboratory Medicine, University of Kentucky Medical Center, Lexington, KY, United States Foreword (from the first edition) Clinicians must make decisions from information presented to them, both by the patient and ancillary resources available to the physician Laboratory data generally provide quantitative information, which may be more helpful to physicians than the subjective information from a patient’s history or physical examination Indeed, with the prevalent pressure for physicians to see more patients in a limited timeframe, laboratory testing has become a more essential component of a patient’s diagnostic work-up, partly as a timesaving measure but also because it does provide information against which prior or subsequent test results, and hence patients’ health, may be compared Tests should be ordered if they could be expected to provide additional information beyond that obtained from a physician’s first encounter with a patient and if the results could be expected to influence a patient’s care Typically, clinicians use clinical laboratory testing as an adjunct to their history taking and physical examination to help confirm a preliminary diagnosis, although some testing may establish a diagnosis, for example molecular tests for inborn errors of metabolism Microbiological cultures of body fluids may not only establish the identity of an infecting organism, but also establish the treatment of the associated medical condition In outpatient practice clinicians primarily order tests to assist them in their diagnostic practice, whereas for hospitalized patients, in whom a diagnosis has typically been established, laboratory tests are primarily used to monitor a patient’s status and response to treatment Tests of organ function are used to look for drug toxicity and the measurement of the circulating concentrations of drugs with narrow therapeutic windows is done to ensure that optimal drug dosing is achieved and maintained The importance of laboratory testing is evident when some physicians rely more on laboratory data than a patient’s own assessment as to how he or she feels, opening them to the criticism of treating the laboratory data rather than the patient In the modern, tightly regulated, clinical laboratory in a developed country few errors are likely to be made, with the majority labeled as laboratory errors occurring outside the laboratory itself One study from 1995 showed that when errors were made 75% still produced results that fell within the reference interval (when perhaps they should not) [1] Half of the other errors were associated with results that were so absurd that they were discounted clinically Such results clearly should not have been released to a physician by the laboratory and could largely be avoided by a simple review by human or computer before being verified However, the remaining 12.5% of errors produced results that could have impacted patient management The prevalence of errors may be less now than previously, since the quality of analytical testing has improved, but the ramifications of each error are not likely to be less The consequences of an error vary depending on the analyte or analytes affected and whether the patient involved is an inpatient or outpatient If the patient is an inpatient a physician, if suspicious about the result, will likely have the opportunity to verify the result by repeating the test or other tests addressing the same physiological functions, before taking action However, if the error occurs with a specimen from an outpatient causing an abnormal result to appear normal, that patient may be lost to follow-up and present later with advanced disease Despite the great preponderance of accurate results clinicians should always be wary of any result that does not seem to fit with the patient’s clinical picture It is, of course, equally important for physicians not to dismiss any result that they not like as a “laboratory error” The unexpected result should always prompt an appropriate follow-up The laboratory has a responsibility to ensure that physicians have confidence in its test results while still retaining a healthy skepticism about unexpected results Normal laboratory data may provide some assurance to worried patients who believe that they might have a medical problem, an issue seemingly more prevalent now with the ready accessibility of medical information available through computer search engines Yet both patients and physicians tend to become overreliant on laboratory information, either not knowing or ignoring the weakness of laboratory tests, in general A culture has arisen of physicians and patients believing that the published upper and lower limits of xiii xiv FOREWORD (FROM THE FIRST EDITION) the reference range (or interval) of a test define normality They not realize that such a range has probably been derived from 95% of a group of presumed healthy individuals, not necessarily selected with respect to all demographic factors or habits that were an appropriate comparative reference for a particular patient Even if appropriate, in 20 individuals would be expected to have an abnormal result for a single test In the usual situation in which many tests are ordered together the probability of abnormal results in a healthy individual increases in proportion to the number of tests ordered Studies have hypothesized that the likelihood of all of 20 tests ordered at the same time falling within their respective reference intervals is only 36% The studies performed to derive the reference limits are usually conducted under optimized conditions such as the time since the volunteer last ate, his or her posture during blood collection and, often the time of day Such idealized conditions are rarely likely to be attained in an office or hospital practice Factors affecting the usefulness of laboratory data may arise in any of the preanalytical, analytical or postanalytical phase of the testing cycle Failures to consider these factors constitute errors If these errors occur prior to collection of blood or after results have been produced, while still likely to be labeled as laboratory errors because they involve laboratory tests, the laboratory staffs are typically not liable for them Yet the staff does have the responsibility to educate those individuals who may have caused them to ensure that such errors not recur If practicing clinicians were able to use the knowledge that experienced laboratorians have about the strengths and weaknesses of tests it is likely that much more clinically useful information could be extracted from existing tests Outside the laboratory, physicians rarely are knowledgeable about the intra- and interindividual variation observed when serial studies are performed on the same individuals For some tests a significant change for an individual may occur when his/her test values shift from toward one end of the reference interval toward the other Thus a test value does not necessarily have to exceed the reference limits for it to be abnormal for a given patient If the preanalytical steps are not standardized when repeated testing is done on the same person, it is more likely that trends in laboratory data may be missed There is an onus on everyone involved in test ordering and test performance to standardize the processes to facilitate the maximal extraction of information from the laboratory data The combined goal should be of pursuit of information rather than just data Laboratory information systems provide the potential to integrate all laboratory data that can then be integrated with clinical and other diagnostic information by hospital information systems Laboratory actions to highlight values outside the reference interval on their comprehensive reports of test results to physicians with codes such as “H” or “L” for high and low values exceeding the reference interval have tended to obscure the actual numerical result and to cement the concept that the upper and lower reference limits define normality and that the presence of one of these symbols necessitates further testing The use of the reference limits as published decision limits for national programs for renal function, lipid or glucose screening has again placed a greater burden on the values than they deserve Every measurement is subject to analytical error, such that repeated determinations will not always yield the same result, even under optimal testing conditions Would it then be more appropriate to make multiple measurements and use an average to establish the number to be acted upon by a clinician? Much of the opportunity to reduce errors (in the broadest sense) rests with the physicians who use test results Over-ordering leads to the possibility of more errors Inappropriate ordering, for example repetitive ordering of tests whose previous results have been normal, or ordering the wrong test or wrong sequence of tests to elucidate a problem should be minimized by careful supervision by attending physicians of their trainees involved in the direct management of their patients Laboratorians need to be more involved in teaching medical students so that when they become residents their test ordering practices are not learned from senior residents who had learned their habits from the previous generation of residents Blanket application of clinical guidelines or test order-sets has probably led to much misuse of clinical laboratory tests Many clinicians and laboratorians have attempted to reduce inappropriate test ordering, but the overall conclusion seems to be that education is the most effective means Unfortunately, the education needs to be continuously reinforced to have a lasting effect The education needs to address the clinical sensitivity of diagnostic tests, the context in which they are ordered and their half-lives Above all education needs to address issues of biological variation and preanalytical factors that may affect test values, possibly masking trends or making the abnormal result appear normal and vice versa FOREWORD (FROM THE FIRST EDITION) This book provides a comprehensive review of the factors leading to errors in all the areas of clinical laboratory testing As such it will be of great value to all laboratory directors and trainees in laboratory medicine and the technical staff who perform the tests in daily practice By clearly identifying problem areas, the book lays out the opportunities for improvement This book xv should be of equal value to clinicians, as to laboratorians, as they seek the optimal outcome from their care of their patients Reference [1] Goldschmidt HMJ, Lent RW Gross errors and workflow analysis in the clinical laboratory Klin Biochem Metab 1995;3:131e49 Donald S Young MD, Ph.D Professor of Pathology and Laboratory Medicine University of Pennsylvania Perelman College of Medicine, Philadelphia, PA Elsevier Radarweg 29, PO Box 211, 1000 AE Amsterdam, Netherlands The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States Copyright © 2019 Elsevier Inc All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/ permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility 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 Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN: 978-0-12-813776-5 For information on all Elsevier publications visit our website at https://www.elsevier.com/books-and-journals Publisher: Stacy Masucci Acquisition Editor: Tari Broderick Editorial Project Manager: Megan Ashdown Production Project Manager: Punithavathy Govindaradjane Cover Designer: Mark Rogers Typeset by TNQ Technologies Preface Clinical laboratory tests have significant impact on patient safety and patient management because more than 70% of all medical diagnosis are based on laboratory test results Physicians rely on hospital laboratories for obtaining accurate results and a falsely elevated or falsely lower value due to interference or pre-analytical errors may have significant influence on diagnosis and management of patients Usually, a clinician questions the validity of a test result if the result does not match with clinical evaluation of the patient and calls laboratory professionals for interpretation However, clinically significant inaccuracies in laboratory results may go unnoticed and mislead the clinicians into inappropriate diagnostic and therapeutic approaches, sometimes with very adverse outcomes The first edition of “Accurate Results in the Clinical Laboratory: A Guide to Error Detection and Correction” was published by Elsevier in 2013 and was intended as a guide to increase awareness of both clinicians and laboratory professionals about the various sources of errors in clinical laboratory tests and what can be done to minimize or eliminate such errors The first edition of the book had 22 chapters and was well received by readers Due to success of the first edition, Elsevier requested a second edition of the book In this edition, we not only updated all chapters of the first edition, but also added new chapters so that the second book could be a concise but comprehensive guide for both clinicians and laboratory professionals to detect errors and sources of misinterpretation in the clinical laboratory and to prevent or correct such results Recently, biotin interferences in immunoassays that utilize biotinylated antibodies have been described which may lead to wrong diagnosis of Grave’s disease due to falsely low TSH (sandwich assay that shows negative interference due to biotin) but falsely elevated T3, T4 and FT4 (competitive immunoassays showing positive biotin interferences) The Food and Drug Administration reported a fatal outcome due to a falsely low troponin value as a result of negative interference of biotin in the troponin assay Because people take megadoses of biotin, this is a serious public health concern Therefore, we added a new chapter (Chapter 8) Another new chapter (Chapter 16) is also added to discuss issues of false negative results in toxicology due to the difficulty in detecting certain drugs such as synthetic cathinone (bath salts) and synthetic cannabinoids (spices) Chapter 27 is also added to discuss sources of errors in flow cytometry Moreover, Chapters 29e31 are also newly added chapters in the second edition The objective of this second edition book is to provide a comprehensive guide for laboratory professionals and clinicians regarding sources of errors and misinterpretation in the clinical laboratory and how to resolve such errors and identify discordant specimens Accurate laboratory result interpretation is essential for patient safety This book is intended as a practical guide to laboratory professionals and clinicians who deal with erroneous results on a regular basis We hope this book will help them to be aware of such sources of errors and empower them to eliminate such errors when feasible or to account for known sources of variability when interpreting changes in laboratory results We would like to thank all contributors for taking time from their busy professional demands to write chapters Without their dedicated contributions this project would never materialize We also thank our families for putting up with us for the last year when we spent many hours during weekends and evenings writing chapters and editing this book Finally our readers will be the judges of the success of this project If our readers find this book useful, all the hard work of contributors and editors will be rewarded Respectfully Submitted Amitava Dasgupta Houston, TX xvii Jorge L Sepulveda New York, NY C H A P T E R Variation, errors, and quality in the clinical laboratory Jorge L Sepulveda Department of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States INTRODUCTION The analytical assay measured the concentration of the analyte corresponding to its “true” level (compared to a “gold standard” measurement) within a clinically acceptable margin of error (the total acceptable analytical error (TAAE)) The report reaching the clinician contained the right result, together with interpretative information, such as a reference range and other comments, aiding clinicians in the decision-making process Recent studies demonstrated that in vitro diagnostic tests are performed in up to 96% of patients and that up to 80% of clinical decisions involve consideration of laboratory results [1] In addition, approximately 40e94% of all objective health record data are laboratory results [2e4] Diagnostic errors accounted for 26e78% of identified medical errors [5] and nearly 60% of malpractice claims [6], and were involved in 17% of adverse effects due to medical errors in one large study [7] Undoubtedly, appropriate ordering and interpretation of accurate test results are essential for major clinical decisions involving disease identification, classification, treatment, and monitoring Factors that constitute an accurate laboratory result involve more than analytical accuracy and can be summarized as follows: Failure at any of these steps can result in an erroneous or misleading laboratory result, sometimes with adverse outcomes For example, interferences with point-of-care glucose testing due to treatment with maltose containing fluids have led to failure to recognize significant hypoglycemia and to mortality or severe morbidity [11] The right test, with the right costs and right method, was ordered for the right patient, at the right time, for the right reason [8]: the importance of appropriate test selection cannot be minimized as studies have shown that at least 20% of all test orders are inappropriate [9], up to 68% of tests ordered not contribute to improve patient management [10] and conversely tests were not ordered when needed in nearly 50% of patients [9] The right sample was collected on the right patient, at the correct time, with appropriate patient preparation The right technique was used collecting the sample to avoid contamination with intravenous fluids, tissue damage, prolonged venous stasis, or hemolysis The sample was properly transported to the laboratory, stored at the right temperature, processed for analysis, and analyzed in a manner that avoids artifactual changes in the measured analyte levels Accurate Results in the Clinical Laboratory, Second Edition https://doi.org/10.1016/B978-0-12-813776-5.00001-7 ERRORS IN CLINICAL LABORATORY Errors can occur in all the steps in the laboratory testing process, and such errors can be classified as follows (see Table 1.1): Pre-analytical steps, encompassing the decision to test, transmission of the order to the laboratory for analysis, patient preparation and identification, sample collection, and specimen processing Analytical assay, which produces a laboratory result Post-analytical steps, involving the transmission of the laboratory data to the clinical provider, who uses the information for decision making Although minimization of analytical errors has been the main focus of developments in laboratory medicine, the other steps are more frequent sources of erroneous Copyright © 2019 Elsevier Inc All rights reserved TABLE 1.1 VARIATION, ERRORS, AND QUALITY IN THE CLINICAL LABORATORY Types of error in the clinical laboratory TABLE 1.1 Types of error in the clinical laboratory.dcont’d PRE-ANALYTICAL ANALYTICAL Test ordering • High analytical turnaround time • Instrument caused random error • Instrument malfunction • QC failure • QC not completed • Duplicate Order • Ordering provider not identified • Ordered test not performed (include add-ons) • Order misinterpreted (test ordered intended test) • Inappropriate/outmoded test ordered • Order not pulled by specimen collector Sample collection • Unsuccessful phlebotomy • Traumatic phlebotomy • Patient complaint about phlebotomy • Check-in not performed (in the LIS) • Wrong patient preparation (e.g., non-fasting) • Therapeutic drug monitoring test timing error Specimen transport • Inappropriate sample transport conditions • Specimen leaked in transit • Specimen damaged during transport • Specimen damaged during centrifugation/analysis Specimen identification • • • • • • • • Specimen unlabeled • Specimen mislabeled: No Name or ID on tube • Specimen mislabeled: No Name on tube • Specimen mislabeled: Incomplete ID on tube • Wrong specimen label • Wrong name on tube • Wrong ID on tube • Wrong blood type Date/time missing Collector’s initials missing Label illegible Two contradictory labels Overlapping labels Mismatch requisition/label Specimen information misread by automated reader High pre-analytical turnaround time • Delay in receiving specimen in lab • Delay in performing test • STAT not processed urgently Specimen quality • Specimen contaminated with infusion fluid • Specimen contaminated with microbes • Specimen too old for analysis • Hemolyzed • Clotted or platelet clumps Specimen containers • No specimens received/ Missing tube • Specimen lost in laboratory • Wrong specimen type • Inappropriate container/tube type • Wrong tube collection instructions • Wrong preservative/ anticoagulant • Insufficient specimen quantity for analysis • Tube filling error (too much anticoagulant) • Tube filing error (too little anticoagulant) • Empty tube • Test perform by unauthorized personnel • Results discrepant with other clinical or laboratory data • Testing not completed • Wrong test performed (different from test ordered) POST-ANALYTICAL • • • • Report not completed Delay in reporting results Critical results not called Delay in calling critical results • Results reported incorrectly • Results reported incorrectly from outside laboratory • Results reported to wrong provider • Reported questionable results, detected by laboratory • Reported questionable results, detected by clinician • Failure to append proper comment • Read back not done • Results misinterpreted • Failure to act on results of tests OTHER • • • • Proficiency test failure Product wastage Product not delivered timely Product recall • • • • Employee injury Safety failure Environmental failure Damage to equipment results An analysis indicated that pre-analytical errors accounted for 62% of all errors, with post-analytical representing 23% and analytical 15% of all laboratory errors [12] The most common pre-analytical errors included incorrect order transmission (at a frequency of approximately 3% of all orders) and hemolysis (approximately 0.3% of all samples) [13] Other frequent causes of preanalytical errors include the following: • Patient identification error • Tube filling error, empty tubes, missing tubes, or wrong sample container • Sample contamination or collected from infusion route • Inadequate sample temperature Particular attention should be paid to patient identification because errors in this critical step can have severe consequences, including fatal outcomes, for example, due to transfusion reactions or misguided therapeutic decisions To minimize identification errors, health care systems are using point-of-care identification systems, which typically involve the following: Handheld devices connected to the laboratory information systems (LIS) that can objectively identify the patient by scanning a patient-attached bar code, typically a wrist band I SOURCES OF ERRORS IN CLINICAL LABORATORIES: AN OVERVIEW INDEX testing process for drug confirmation, 244e246 urine samples, 243 Drug Enforcement Administration (DEA), 259e261 Drug-drug interactions, 224 Drug-herb interactions, 297, 306e312, 312t Drugs of abuse (DAU), 69 POC devices, 452e454 testing, 233 Drunkometer, 461 DRVVT See Dilute Russell viper venom time (DRVVT) DSTRs See Delayed serologic transfusion reaction (DSTRs) DT See Delirium tremens (DT) DTRs See Delayed transfusion reactions (DTRs) DUI See Driving under the influence (DUI) DW See Dextrose in water (DW) DWI See Driving while intoxicated (DWI) Dysfibrinogenemia, 395 E EC See N-Ethylcathinone (EC) ECD See Extracellular domain (ECD) Echinacea, 295 ECHOs See Environmental Influences on Child Health Outcomes (ECHOs) EDDP See 2-Ethylidene-1,5-dimethyl-3,3diphenylpyrolidine (EDDP) EDs See Emergency departments (EDs) EDTA See Ethylenediamine tetraacetic acid (EDTA) Efavirenz, 240 EGCG See Epigallocatechin 3-gallate (EGCG) EGFR See Epidermal growth factor receptor (EGFR) eGFR See Estimated glomerular filtration rate (eGFR) Egg white disease, 87 EGTA See Ethyleneglycol-tetraacetic acid (EGTA) EIA See Enzyme immunoassay (EIA) ELECSYS automated immunoassay system, 70e71 Electrolyte analysis, 116e128 analytical issues, 124 calcium, 116, 119 CO2 assay, 121 magnesium, 116, 119 phosphate, 121e122, 124 physiologic pre-analytical issues, 119e122 specimen issues, 122e124 Electrolytes, 218 Electrophoresis, 366 ELISA See Enzyme-linked immunosorbent assay (ELISA) EMCDDA See European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) Emergency departments (EDs), 174, 271 EMIT See Enzyme multiplied immunoassay (EMIT) Endocrine hormone measurements, 165 Endocrinology testing ACTH, 171e172 adrenal function tests, 176e178 aldosterone and rennin, 177e178 cortisol, 176e177 GH, 170e171 gonadal and reproductive medicine, 179e180 hCG, 174e175 hormonal analysis, 166e170 assay specificity, 166 biotin ingestion-associated interference, 168e170 HAMAs, RF, heterophile antibodies, 167e168 high-dose hook effect, 166e167 macro-complexes, 167 hormones including insulin, 181 IGF-I, 180 age, 180 binding proteins, 180 sex, 180 LH/FSH, 173 pre-analytical considerations, 165e166 prenatal testing, 181e182 Prl, 173e174 PTH, 178e179 sample collection and processing, 165e166 testing of hormones secreted by pituitary, 170e174 thyroid function tests, 175e176 CT, 176 thyroglobulin, 175e176 TSH, 172e173 Endogenous antibodies, 172 Endogenous interferences, 218 See also Heterophilic antibodies interfering substances, 227 substances, and laboratory tests evaluation of, 65 hemolysis, 58e63 icterus and, 64e65 lipemia, 63e64 Enoxacin, 237 Enterovirus, 378 Environmental Influences on Child Health Outcomes (ECHOs), 46 Enzymatic assays, 101 creatinine assays, 108e109 hydrolysis, 263e264 methods, 127 Enzymatic alcohol assays, 277e281 existing automated testing methods, 278e281 cross reactivity with alcohols, 279e280 elevated lactate and LDH, 280e281 Enzyme immunoassay (EIA), 324e327 Enzyme multiplied immunoassay (EMIT), 70, 220 477 Enzyme-linked immunosorbent assay (ELISA), 70e71, 175, 397 Ephedra, 302 Ephedrine, 236, 300e301 Ephedrone, 259te260t Epicatechin, 300 Epicatechin gallate, 300 Epidermal growth factor receptor (EGFR), 207, 353e354 Epigallocatechin, 300 Epigallocatechin 3-gallate (EGCG), 300 ERBB2 gene, 206 ERNDIM See European Research Network for evaluation and improvement of screening, Diagnosis and treatment of Inherited Disorders of Metabolism (ERNDIM) Errors, in clinical laboratory, 3e6, 4t active, analytical, clinical acceptability, cognitive vs noncognitive, and cross-contamination of specimens, 37 latent/system, minimization, approaches to, 5e6 outcomes, post-analytical, pre-analytical, random, 7, 7f reporting of, 5, 6f sources, systematic, 7, 7f TAE, 7, 7f Errors in transfusion, 439e440 Erythrocytes, 13 Eskalith, 228 Estazolam (ProSom), 252 Estimated glomerular filtration rate (eGFR), 103e105, 452 Estradiol assays, 166 Estrogens, 166 Ethanol, 120 determination using automated analyzers alcohol measurement methods, 275e276 eliminating interferences in alcohol assays, 281e284 enzymatic alcohol assays, 277e281 markers of ethanol ingestion, 284e287 pharmacodynamics, 272e273 pharmacokinetics, 273e275 quantity of ethanol consumed for drinking levels, 272t toxic alcohols, 287e288 ingestion markers, 284e287 biochemical abnormalities, 287 ethyl glucuronide, ethyl sulfate, PEth, FAEEs, 286e287 OG, 285e286 Ethnicity/race effect, on clinical laboratory test results, 54 Ethyl glucuronide, 286e287 478 Ethyl sulfate, 286e287 N-Ethyl-N-(2-hydroxy-3-sulfopropyl)m-toluidine (TOOS), 149 N-Ethylcathinone (EC), 259te260t Ethylenediamine tetraacetic acid (EDTA), 11, 111e112, 165e166, 341e342, 387, 391 potassium, 18 spray-dried potassium, 18 Ethyleneglycol-tetraacetic acid (EGTA), 127 2-Ethylidene-1,5-dimethyl-3,3diphenylpyrolidine (EDDP), 237e238, 250 screening, 238 Ethylone, 259te260t European Directive 2004/24/EC, 295e296 European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), 240, 259e261 European Research Network for evaluation and improvement of screening, Diagnosis and treatment of Inherited Disorders of Metabolism (ERNDIM), 368 Everolimus, 225 Exercise effect, on clinical laboratory test results, 52e53, 54t EXO/SAP See Exonuclease I and shrimp alkaline phosphatase (EXO/SAP) Exogenous factors, 178e179 Exogenous interferences, 218 Exonuclease I and shrimp alkaline phosphatase (EXO/SAP), 351 Extensive chromatographic separation, 267 Extracellular domain (ECD), 206 Extravascular hemolysis, 441 F FAA See Federal Aviation Administration (FAA) FAAS See Flame atomic absorption spectrometry (FAAS) FAD See Flavin adenine dinucleotide (FAD) FAEEs See Fatty acid ethyl esters (FAEEs) FAES See Flame atomic emission spectrophotometry (FAES) Failure review analysis and corrective action system (FRACAS), 5e6 False negatives, 244, 332 results in toxicology abuse of NPS, 257e259 confirmation of NPS, 267e269 limitations of NPS immunoassays, 266e267 NPS in biological matrix, 264e266 False positive, 244 AFP, 199 osmotic fragility test, 391 sickle cell solubility test, 323 Falsely-high WBC counts, 388 FAO defects See Fatty acid oxidation defects (FAO defects) INDEX FASDs See Fetal alcohol spectrum disorders (FASDs) Fasting and clinical laboratory test results, 12 effect, on clinical laboratory test results, 50 lipid profiles, 134e135 Fatty acid concentration, 216 Fatty acid ethyl esters (FAEEs), 286e287 Fatty acid oxidation defects (FAO defects), 372e373 Fatty liver, 273 FCS See Forward scatter (FCS) FDA See U.S Food and Drug Administration (FDA) FDP See Fibrin/Fibrinogen Degradation Products (FDP) Febrile nonhemolytic transfusion reactions (FNHTRs), 441e442 Federal Aviation Administration (FAA), 459e460 Fenofibrate, 177, 236 Fentanyl, 236 analogues abuse, 258e259, 260f screening, 238 Fenugreek, 303, 303t Fetal alcohol spectrum disorders (FASDs), 273 FFPE See Formalin fixation and paraffin embedding (FFPE) Fibrin/Fibrinogen Degradation Products (FDP), 396 Fibrin/Fibrinogen Split Products (FSP), 396 Fibrinogen, 18e19, 329 Fibrinolysis products, 396e397 Ficus carica (Fig leaves), 303 FISH See Fluorescence in situ hybridization (FISH) Flame atomic absorption spectrometry (FAAS), 228e229 Flame atomic emission spectrophotometry (FAES), 228e229 Flavin adenine dinucleotide (FAD), 115 Flavonoids, 303 FLC immunoassay See Free light chain immunoassay (FLC immunoassay) Flow analysis, 408e410 Flow cytometry, 401 analysis of fluids, 413 cell doublets, 407e408, 407f cell viability, 401e404 clotting, cell clumping and laminar flow, 406e407 human factor, 419e421 case scenario, 419e421 Mab therapies, 410e413 paraproteins and flow analysis, 408e410 platelet aggregates, 408 sample transit times, 404e406 specimen quality, 401e413 technological challenges in, 413e419 compensation, 413e414 spillover beyond compensation, 414e416 strange case of calcium oxalate and CSF, 418e419 Tandem dyes, 416e418, 417t Flow intracellular staining techniques, 402e403 Fluids, flow cytometry analysis of, 413 Flunitrazepam (Rohypnol), 252e253 Fluorescence in situ hybridization (FISH), 206, 339e340, 355e356 Fluorescent polarization immunoassay (FPIA), 70, 220 Fluoride, 30 Fluorochrome-labeled antihuman globulin, 332 Fluorometer, 339 3-Fluoromethcathinone (3-FMC), 259te260t 4-Fluoromethcathinone (4-FMC), 259te260t Fluorophores, 414e415 Fluoxetine, 216 Flurazepam, 252 3-FMC See 3-Fluoromethcathinone (3-FMC) 4-FMC See 4-Fluoromethcathinone (4-FMC) FNHTRs See Febrile nonhemolytic transfusion reactions (FNHTRs) Follicle stimulating hormone (FSH), 46, 172 Food ingestion and clinical laboratory test results, 49 Food-drug interactions, 217 Formaldehyde, 287 Formalin fixation and paraffin embedding (FFPE), 337e338 Foărster resonance energy transfer (FRET), 416e417 Forward scatter (FCS), 407e408 Fosphenytoin, 224e225 Foxglove See Digitalis purpurea (foxglove) FPD See Freezing point depression (FPD) FPIA See Fluorescent polarization immunoassay (FPIA) FRACAS See Failure review analysis and corrective action system (FRACAS) Fragmented genomic DNA, 353 Fragmented red cells, 389 Free hemoglobin, 59e60 “Free insulin”, 181 Free light chain immunoassay (FLC immunoassay), 330e331 Free T4 See Free thyroxine (FT4) Free thyroxine (FT4), 48, 172 Free-flowing puncture technique, 396 Freezing point depression (FPD), 285 FRET See Foărster resonance energy transfer (FRET) FSH See Follicle stimulating hormone (FSH) FSP See Fibrin/Fibrinogen Split Products (FSP) FT4 See Free thyroxine (FT4) a-Fucosidase (FUCA1 gene), 374 Fuel cell based technology, 462t INDEX Functional assays, 401 Functional sensitivity, 153 Furanocoumarins, 313e314 Furanylfentanyl, 259 G G6PD See Glucose-6-phosphate dehydrogenase (G6PD) GAA gene See a-Glucosidase (GAA gene) a-Galactosidase (GLA gene), 374 b-Galactosidase (GLB1 gene), 374 Gallocatechin, 300 Gamma-glutamyl transferase (GGT), 30e31, 46, 48, 111e112, 146e147, 202, 297e298 analytical issues, 147 Gan Cao, 300e301 Garlic, 295, 303, 303t, 306 Gas chromatography (GC), 245e246, 277, 288, 462 Gas chromatography mass spectrometry (GCeMS), 177, 235e236, 241, 244e245, 265e266, 366, 369e371, 452e453 Gastro-esophageal reflux disease (GERD), 466 breath alcohol analysis and, 466 Gastrointestinal stromal tumors (GISTs), 356e357 GC See Gas chromatography (GC) GCeMS See Gas chromatography mass spectrometry (GCeMS) GDH See Glucose dehydrogenase (GDH) Gel separator tubes, 30 GenBank, 344 Gene duplications, 358e359 Gene expression microarrays, 340 Genetic polymorphisms, 217 Genetic variation, 343e344 Genotyping, 358, 373 GERD See Gastro-esophageal reflux disease (GERD) Germander See Teucrium chamaedrys (Germander) Germline databases, 342e343 variants, 353 GFR See Glomerular filtration rate (GFR) GGT See Gamma-glutamyl transferase (GGT) GH See Growth hormone (GH) GHRH See Growth hormone-releasing hormone (GHRH) Ginger, 295, 303, 303t Ginkgo biloba, 295, 306 drug interactions with, 311 Ginseng, 295, 303, 303t GISAH See Global Information System on Alcohol and Health (GISAH) GISTs See Gastrointestinal stromal tumors (GISTs) Gitelman syndrome, 305 GLA gene See a-Galactosidase (GLA gene) Glanzmann’s thrombasthenia, 390 Glass tubes, 16 GLB1 gene See b-Galactosidase (GLB1 gene) Global Information System on Alcohol and Health (GISAH), 271 Glomerular filtration rate (GFR), 46, 48, 54e55, 103, 217 Glucagon, 181 Glucose, 303 analysis, 113e116 interferences in, 115e116 methodology, 115 pre-analytical considerations, 114e115 assay, 103 fasting and, 12 methodological issue of POC devices, 452 Glucose dehydrogenase (GDH), 115e116 Glucose oxidase, 115 reaction, 101 Glucose-6-phosphate dehydrogenase (G6PD), 33e34 a-Glucosidase (GAA gene), 374 b-Glucuronidase (GUSB gene), 374 Glucuronidation, 263e264 Glucuronide conjugates, 252 moiety, 239 Glue sniffing, 466, 467t Glutamate dehydrogenase, 110 g-Glutamyl-p-nitroaniline, 147 Glycerol kinase, 136 P-Glycoprotein, 51 Glycosyl phosphatidyl inositol (GPI), 199, 441 Glycosylated hemoglobin, 303 Goldenseal, 306 Gonadal and reproductive medicine, 179e180 GOT1 gene, 143 GOT2 gene, 143 Gotu kola See Centella asiatica (Gotu kola) Gout, 112 GPI See Glycosyl phosphatidyl inositol (GPI) GPT gene, 143e144 Grapefruit juice-drug interactions, 313e314, 314t Green tea extract, 300, 301t Group O strains, 324e325 Growth hormone (GH), 170e171, 171t Growth hormone-releasing hormone (GHRH), 170 Gurmar See Gymnema sylvestre (gurmar) GUSB gene See b-Glucuronidase (GUSB gene) Gymnema sylvestre (gurmar), 303, 303t H H2O2-based methods See Hydrogen peroxide-based methods (H2O2-based methods) HAAA See Human anti-animal antibodies (HAAA) 479 Hair, 243, 265 Haldane effect, 130 Haloperidol, 216 HAMA See Human anti-mouse antibody (HAMA) Handheld devices, Haplotypes, 353 Haptoglobin, 59 HARA See Human anti-rabbit (HARA) HAV See Hepatitis A virus (HAV) Hb Bart’s, 323e324 Hb S See Hemoglobinopathy S (Hb S) HbA See Hemoglobin A (HbA) HbA2 See Hemoglobin A2 (HbA2) HbA20 , 323, 323t HbAS See Sickle cell trait (HbAS) HbC See Hemoglobin C (HbC) HbD See Hemoglobin D (HbD) HBD See Hydroxybutyrate Dehydrogenase (HBD) HbE See Hemoglobin E (HbE) HbF See Hemoglobin F (HbF) HbG See Hemoglobin G (HbG) HBR See Heterophilic blocking reagent (HBR) HbS See Hemoglobin S (HbS) HBsAg See Hepatitis B surface antigen (HBsAg) HbSS See Sickle cell disease (HbSS) HBV See Hepatitis B virus (HBV) HCC See Hepatocellular carcinoma (HCC) HCD See Heavy chain disease (HCD) HCFA See Health Care Financing Administration (HCFA) hCG See Human chorionic gonadotropin (hCG) hCGb core fragment (hCG-bcf), 174 HCT See Hematocrit (HCT) HCV See Hepatitis C virus (HCV) HDFN See Hemolytic disease of fetus and newborn (HDFN) HDL See High density lipoprotein (HDL) HDL-C See High-density lipoproteinassociated cholesterol (HDL-C) HDV See Hepatitis D virus (HDV) HE4 See Human epididymis protein (HE4) Health and Human Services (HHS), 244 HHS-certified laboratories, 253, 254t Health care failure modes and effects analysis (HFMEA), 5e6 Health Care Financing Administration (HCFA), 102 Heart failure (HF), 154 Heavy chain disease (HCD), 330 Heavy metals, 313 Hemagglutination, 389e390 Hematocrit (HCT), 13, 387 delta checks, 38e39 effect in breath alcohol analysis, 464 Hematogones, 403e404 Hematological malignancies, 428 Hematology testing, errors in, 387, 389e391, 391te392t cold agglutinins, 389e390 480 Hematology testing, errors in (Continued ) cryoglobulins, 390 errors related to sample collection, transport and storage, 391e392 false positive osmotic fragility test, 391 hemoglobin measurement and RBC count, 388 MCV and related measurements, 388 platelet count, 389 pseudothrombocytopenia, 390 spurious leukocytosis, 391 WBC counts and WBC differential count, 388e389 Hemoglobin (Hgb), 15, 59, 142, 341e342 disorders, 323, 323t errors in Hgb measurement, 388 variants, 455 Hemoglobin A (HbA), 322 Hemoglobin A1c (HbA1c), 18, 454 Hemoglobin A2 (HbA2), 323 Hemoglobin C (HbC), 322e323, 323t Hemoglobin D (HbD), 323, 323t Hemoglobin E (HbE), 323, 323t Hemoglobin F (HbF), 130e131, 323e324, 454 Hemoglobin G (HbG), 323, 323t Hemoglobin O (HbO, 323, 323t Hemoglobin S (HbS), 322e323, 323t Hemoglobinopathies, 388 Hemoglobinopathy detection challenges in, 321e324, 324t HIV testing, 324e325 diagnosis errors, 322e324 Hb S, 324 HbA2, 323 HbF, 323 hemoglobin disorders, 323t methodologies, 322t Hemoglobinopathy S (Hb S), 324 Hemoglobinopathy screening, 322 Hemolysis, 22e23, 217e218, 441 causes, 57e58 effect on laboratory tests, 58e63 in vitro, 59t, 60e62, 61t in vivo, 59e60, 59t Hemolytic disease of fetus and newborn (HDFN), 426 Hemolytic transfusion reactions (HTR), 426 Hemostasis, 395 Henry’s law, 460 Hep2 cells See Human epithelial tumor cell line cells (Hep2 cells) Heparin, 18e19, 395, 397e398, 455 Hepatic iron, 444 Hepatic lipase, 147e148 Hepatitis infection, 325e326 testing, 325e327 hepatitis B serology, 326, 326t hepatitis C serology, 326e327 Hepatitis A virus (HAV), 325e326 Hepatitis B surface antigen (HBsAg), 167e168, 326 Hepatitis B virus (HBV), 325e326 INDEX Hepatitis C virus (HCV), 326e327 Hepatitis D virus (HDV), 325e326 Hepatitis E virus (HEV), 325e326 Hepatocellular carcinoma (HCC), 191e192, 198 Hepatocellular toxicity, 298 Hepatotoxicity, 298 Hepcidin, 160 Heptafluorobutyric anhydride (HFBA), 245e247 HER2 See Human epidermal growth factor receptor (HER2) Herbal life, 301t Herbal medicines, 223e224 Herbal remedies, 295 Herbal supplements and abnormal liver function tests, 297e301 abnormal thyroid function tests, 305e306 adulteration with oral hypoglycemic agents, 304e305 affecting laboratory test, 297 abnormal laboratory test results, 297t with antidiabetic activity, 303t associated with kidney damage, 301e302 associated with liver damage, 300e301, 301t chaparral, 300 coltsfoot, 299 comfrey, 299 drug interactions with ginkgo biloba, 311 drug-herb interactions, 306e312, 312t FDA warnings to toxic herbs, 296e297 germander, 299 grapefruit juice-drug interactions, 313e314, 314t green tea extract, 300 and hypoglycemia, 303e305 hypokalemia, 305 issues with variable active ingredients and poor manufacturing practice, 296 kava, 298e299 kava-drug interactions, 311 kelp, 305e306 licorice, 305 overview, 295e296 pennyroyal, 300 St John’s wort interaction with various drugs, 306e309 warfarin interactions with, 310e311 Herbs adulterated with western drugs, 312e313 interfering with digoxin immunoassays, 314 Herceptin, 192 Hereditary persistence of fetal hemoglobin (HPFH), 323 Heroin, 236e237, 249 Heteroblock, 80 Heterogeneous immunoassays, 70e71 Heterophile antibodies, 167e168, 177, 180, 197 interferences, 75e78, 176 detection and correction, 79e81 mechanism, 76 problematic, 77e78 removal of interfering substances, 80e81 Heterophilic blocking reagent (HBR), 80 Heterophilic interference, 75 Hetrophilic antibody interference in tumor markers testing, 206e207 HEV See Hepatitis E virus (HEV) HEXA gene See b-Hexosaminidase (HEXA gene) Hexagonal phospholipid neutralization procedure, 397e398 Hexokinase, 115e116 b-Hexosaminidase (HEXA gene), 374 HF See Heart failure (HF) HFBA See Heptafluorobutyric anhydride (HFBA) HFMEA See Health care failure modes and effects analysis (HFMEA) Hgb See Hemoglobin (Hgb) HHA See 3,4-Dihydroxyamphetamine (HHA) HHb See Deoxyhemoglobin (HHb) HHH See HyperornithinemiaHyperammonemiaHomocitrullinuria (HHH) HHMA See 3,4Dihydroxymethamphetamine (HHMA) HHS See Health and Human Services (HHS) HI RBC antigens See High-incidence RBC antigens (HI RBC antigens) High density lipoprotein (HDL), 47e49 High molecular mass glycoprotein, 205e206 High performance liquid chromatography (HPLC), 241, 321, 322t High-density lipoprotein-associated cholesterol (HDL-C), 134 High-dose hook effect, 166e167, 174 High-incidence RBC antigens (HI RBC antigens), 432e433 High-resolution mass spectrometric (HR-MS), 261 Hirudin, 19 HIV See Human immunodeficiency virus (HIV) HIV testing challenges in, 324e325 combined antibody antigen tests, 325 confirmation tests, 325 rapid HIV antibody tests, 325 methods, 325t HLA See Human leukocyte antigen (HLA) HLA 5701, 357 HLA-B locus *5701 allele, 357 HLA-B*15:02 allele, 357e358 HMA See 4-Hydroxy-3-methoxy amphetamine (HMA) INDEX HMMA See 4-Hydroxy-3methoxymethamphetamine (HMMA) Homogeneous immunoassays, 70 Hook effect See Prozone effect Hormonal analysis, 166e170 assay specificity, 166 biotin ingestion-associated interference, 168e170 HAMAs, RF, heterophile antibodies, 167e168 high-dose hook effect, 166e167 macro-complexes, 167 Hormones, 181 See also Endocrinology testing assay interferences, 173 secreted testing by pituitary, 170e174 ACTH, 171e172 GH, 170e171 LH/FSH, 173 Prl, 173e174 TSH, 172e173 HPA See Human platelet antigen (HPA) HPFH See Hereditary persistence of fetal hemoglobin (HPFH) HPLC See High performance liquid chromatography (HPLC) HPLC-tandem mass spectrometry (HPLC-MS/MS), 368e369 HPPH See 5-(p-Hydroxyphenyl)-5phenylhydantoin (HPPH) HR-MS See High-resolution mass spectrometric (HR-MS) hTHTR2 (thiamine transporter), 87 HTR See Hemolytic transfusion reactions (HTR) Huang Qin, 300e301 Human anti-animal antibodies (HAAA), 78e79, 204e205 Human anti-mouse antibody (HAMA), 75e76, 78, 167e168, 197, 206e207, 454 Human anti-rabbit (HARA), 79 Human chorionic gonadotropin (hCG), 47, 76, 167e168, 174e175, 192, 203e205 diet, 50 false positive, 204e205 high-dose hook effect, 174 persistent low levels, 203e204 tests, 454 Human epidermal growth factor receptor (HER2), 192, 206 Human epididymis protein (HE4), 192 Human epithelial tumor cell line cells (Hep2 cells), 332 Human factor, 419e421 Human genetic variation, 358 Human immunodeficiency virus (HIV), 321 HIV-1/HIV-2 differentiation immunoassay, 325 types and groups, 325t Human leukocyte antigen (HLA), 353, 357, 441 Human platelet antigen (HPA), 443 Humidity, 31 Hybridization of primers, 344 probes, 344 Hydrochloric acid (HCl), 47, 245 Hydrocodone, 237, 250 Hydrogen peroxide-based methods (H2O2-based methods), 108e109 Hydrolysis, 263e264 Hydromorphone, 237, 250 4-Hydroxy-3-methoxy amphetamine (HMA), 248 4-Hydroxy-3-methoxymethamphetamine (HMMA), 248 Hydroxybutyrate Dehydrogenase (HBD), 281 Hydroxychloroquine, 239 Hydroxycut, 296e297, 301t Hydroxyl groups, 271 5-(p-Hydroxyphenyl)-5-phenylhydantoin (HPPH), 225 Hydroxyurea, 323 25-Hydroxyvitamin D (25-OHD), 179 Hyper-proinsulinopathies, 181 Hypercalcemia, 48 Hyperglycemia, 113 Hyperinsulinic hypoglycemia, 113 Hyperinsulinism, 165 Hyperornithinemia-HyperammonemiaHomocitrullinuria (HHH), 369 Hyperprolactinemia, 166t Hyperuricemia, 112 Hypogammaglobulinemia, 330 Hypoglycemia, 113 herbal supplements and, 303e305 Hypokalemia, 305 Hypotension, 444 Hypouricemia, 112 I ICP-MS See Inductively-coupled plasma mass spectrometry methods (ICP-MS) Icterus effect on laboratory tests, 64e65 ICU See Intensive care unit (ICU) ID See Infectious disease (ID) IDMS See Isotope dilution mass spectrometry (IDMS) IDSA See Infectious Diseases Society of America (IDSA) a-Iduronidase (IDUA gene), 374 IEF See Isoelectric focusing (IEF) IEM See Inborn errors of metabolism (IEM) IFCC See International Federation of Clinical Chemistry (IFCC) IFE studies See Immunofixation studies (IFE studies) Ig See Immunoglobulins (Ig) IGF binding protein-3 (IGFBP-3), 180 IGF-I See Insulin-like growth factor I (IGF-I) IgG See Immunoglobulin G (IgG) IIR See Immunoglobulin inhibiting reagent (IIR) 481 Illumina platforms, 342 Immulite, 70e71 assays, 84 Immunoassays, 101, 165e166, 244, 250, 266, 452 analytes, 73t antibodies in, 69e70 biotin in, 83 CEDIA, 70 competition, 69 EMIT, 70 HAAA, 78e79 HAMA, 75e76, 78 heterogeneous, 70e71 homogeneous, 70 interferences, 234e241 amphetamines, 234 benzodiazepines, 239e240 buprenorphine screening, 239 cannabinoids, 240e241 fentanyl screening, 238 methadone/EDDP screening, 238 opiates screening assays, 237e238 opioids, 236e237 from over counter and prescription medication, 236 oxycodone screening, 238e239 limitations, 72, 75 LOCI, 70 methods and assay principle, 69e71 nephelometric, 70 overview, 69 plasma in, 71 reagents, 71e72 RIA, 70e71 sandwich, 69e70 for screening of drugs of abuse in urine interferences, 234e241 LC-MS for confirmation, 241 specimen adulteration, 234 specimen types for, 72 technologies, 219e220 types, 69, 71t Immunodiagnostic Systems immunoassays, 84 Immunofixation studies (IFE studies), 330 Immunoglobulin G (IgG), 341e342, 426e427 Immunoglobulin inhibiting reagent (IIR), 80 Immunoglobulins (Ig), 75e76, 172, 426e427 Immunology and serology testing, 329 ANA, 331e332 hemoglobinopathy detection challenges in, 321e324, 324t diagnosis errors, 322e324 hemoglobin disorders, 323t methodologies, 322t hepatitis testing, 325e327 hepatitis B serology, 326, 326t hepatitis C serology, 326e327 monoclonal protein detection, 329e331 capillary zone electrophoresis, 330 CSF electrophoresis, 331 482 Immunology and serology testing (Continued ) FLC immunoassay, 330e331 hypogammaglobulinemia, 330 IFE studies, 330 Immunometric immunoassays See Sandwich immunoassays Immunophenotype, 407, 411, 420 Immunosuppressants, 225e227, 226t analytical variables, 226e227 case example, 227 drug metabolites, 226 endogenous interfering substances, 227 pre-analytical variables, 226 IMPDH See Inosine monophosphate dehydrogenase (IMPDH) IMx See MEIAtacrolimus (IMx) In vitro hemolysis, 15, 59e62, 59t, 61t In vitro metabolism, 216 In vitro spiking studies, 84 In vivo hemolysis, 59e62, 59t, 61t Inborn errors of metabolism (IEM), 365 indels See Insertion-deletion variants (indels) Individualized Quality Control Plan (IQCP), 382e383, 456 Inductively-coupled plasma mass spectrometry methods (ICP-MS), 228e229 Indwelling catheters for blood specimen collection, 21e23 Infectious disease (ID), 454 Infectious Diseases Society of America (IDSA), 379 INFINITI platform, 351 Infrared based technology, 462t Infrared spectroscopy (IR spectroscopy), 461e462 Inherited metabolic disorders, 365e366 Inhibition mechanisms, 341 Inorganic phosphate, 127 Inosine monophosphate dehydrogenase (IMPDH), 225e226 INR See International normalized ratio (INR) Insertion-deletion variants (indels), 353 Insulin, 181 Insulin-like growth factor I (IGF-I), 38, 180 age, 180 binding proteins, 180 sex, 180 INT See Iodonitrotetrazolium violet dye (INT) “Intact PTH”, 178 Intensive care unit (ICU), 109 Interferences, 206, 221e224 in basic blood bank testing, 427e436 in ABO/Rh typing, 428 in antibody identification, 429 case studies, 429e436 in digoxin measurement, 221e224 from over counter and prescription medication, 236 Interfering substances, 178 INDEX Internal standard (IS), 245 International Federation of Clinical Chemistry (IFCC), 148e149, 280e281 International normalized ratio (INR), 19, 51, 306, 311, 359, 455 International Organization for Standardization (ISO), 261 International Society of Blood Transfusion (ISBT), 439 Intestinal lipase, 147e148 Intraductal papillary mucinous neoplasm (IPMN), 201e202 Intravascular hemolysis, 330 Intravenous immunoglobulin (IVIG), 126 Intravenous lines for blood specimen collection, 21e23 Iodine pentoxide, 461 Iodonitrotetrazolium violet dye (INT), 276 Ion-selective electrodes See Ion-specific electrodes (ISEs) Ion-specific electrodes (ISEs), 124, 228e229 Ionized calcium, 33 IonTorrent platforms, 342 IPMN See Intraductal papillary mucinous neoplasm (IPMN) IQCP See Individualized Quality Control Plan (IQCP) IR spectroscopy See Infrared spectroscopy (IR spectroscopy) Iron chelation therapy, 445 chelators, 445t overload, 444e445, 444t studies, 156e160 emerging markers in iron metabolism, 159e160 IS See Internal standard (IS) ISBT See International Society of Blood Transfusion (ISBT) ISEs See Ion-specific electrodes (ISEs) ISO See International Organization for Standardization (ISO) Isobaric compounds, 369 Isobaric substances, 267 Isoelectric focusing (IEF), 321e322, 322t Isopropyl alcohol, 467t Isotope dilution mass spectrometry (IDMS), 105 Ivacaftor, 360 IVIG See Intravenous immunoglobulin (IVIG) Ivy ground See Coccinia indica (Ivy ground) J Jaffe reaction, 101 Jaffe-based methods, 106e108 Jambrulin, 313 Jendrassik and Grof method (J/G method), 133 Juvenile myelomonocytic leukemia (JMML), 323 JWH-018, 258 K Kampo medicines, 300e301 Kava, 295, 298e299, 301t, 306 kava-drug interactions, 311 Kavain, 298 Kavalactones, 298 Kelp, 305e306 Ketoacidosis, 108 2-Ketoacids, 369e371 Ketogenic diet, 49e50, 467t Kidney damage, herbal supplements associated with, 301e302 Kinetic interaction ofmicroparticle in solution (KIMS), 70 KIT (kinase receptor), 356e357 Klonopin See Clonazepam KOH See Potassium hydroxide (KOH) Kombucha Tea, 301 KRAS, 353e355 L L/P reaction See Lactate-to-Pyruvate reaction (L/P reaction) Laboratory developed tests (LDTs), 366, 378 Laboratory information systems (LIS), 4, 35, 38, 451 Lactate analysis, 131e132 analytical issues, 131e132 Lactate dehydrogenase (LDH), 15, 29, 58, 101, 146, 279e281, 280t analysis, 149e150 Lactate oxidase, 131e132 Lactate, 131 Lactate-to-Pyruvate reaction (L/P reaction), 280e281 Lactovegetarians, 49e50 Laminar flow, 406e407 Lanoxin, 221 Lapses, Laser, 413 Latent errors, Latex agglutination, 396 inhibition method, 452e453 LC See Liquid chromatography (LC) LC-MS See Liquid-chromatography mass spectrometry (LC-MS) LC-MS/MS See Liquid chromatographytandem mass spectrometry (LC-MS/MS) LD See Lactate dehydrogenase (LDH) LDH See Lactate dehydrogenase (LDH) LDL See Low density lipoprotein (LDL) LDL-C See Low density lipoprotein cholesterol (LDL-C) LDTs See Laboratory developed tests (LDTs) Leech (Hirudo medicinalis), 19 Lepirudin, 398 LescheNyhan syndrome, 112 Leukoagglutination, 391 Leukocyte reduction (LR), 441e442 Levofloxacin, 237 Levomepromazine, 238 INDEX LH See Luteinizing hormone (LH) LH/FSH See Luteinizing hormone/ follicle stimulating hormone (LH/FSH) Librium See Chlordiazepoxide Licorice, 302, 305 Ligand assays, 101 LightCycler technology, 350 Limit of detection (LOD), 244 Limit of quantitation (LOQ), 244 Linear ion trap, 268 Lipase analysis, 147e149 analytical issues, 148e149 Lipemia effect on laboratory tests, 64 interference effects of, 63e64 Lipid profile analysis, 134e136 analytical issues, 135e136 fasting and nonfasting lipid profiles, 134e135 pre-analytical considerations, 135 LipoKinetics, 301 LipoKinetix, 296e297, 301t Lipophilic drugs, 217 Lipoprotein lipase, 147e148, 216 Liquid chromatography (LC), 246e247 Liquid chromatography-tandem mass spectrometry (LC-MS/MS), 72, 177, 179, 220, 241, 244e246, 257, 366, 369 Liquid detection formats, 340 Liquid heparin, 128 Liquid-chromatography mass spectrometry (LC-MS), 176, 241, 246, 366 Liquid-liquid extraction (LLE), 263 LIS See Laboratory information systems (LIS) LISS See Low ionic strength solution (LISS) Lithane, 228 Lithiumcarbonate, 228 Liver, 297e298 herbal supplements associated with liver damage, 300e301, 301t toxicity, 301 LLE See Liquid-liquid extraction (LLE) Lobelia, 302 LOCI See Luminescent oxygen channeling immunoassay (LOCI) LOD See Limit of detection (LOD) LOQ See Limit of quantitation (LOQ) Lorazepam (Ativan), 252 Low density lipoprotein (LDL), 63e64 Low density lipoprotein cholesterol (LDL-C), 49e50, 134 Low ionic strength solution (LISS), 429 LR See Leukocyte reduction (LR) Lu-Shen-Wan, 314 Lumacaftor/ivacaftor, 360 Luminescent oxygen channeling immunoassay (LOCI), 70 Luminex xMAP technology, 72 Luminex xTAG assay, 358 Lung function and breath alcohol analysis, 464 Lupus anticoagulant screening assays, 397e398 Luteinizing hormone (LH), 46, 172 Luteinizing hormone/follicle stimulating hormone (LH/FSH), 173 Lymphoma, 203 Lysosomal storage disorders, 373e374 M M protein See Monoclonal protein (M protein) m-CPP See Metabolitemchlorophenylpiperazine (m-CPP) Ma huang, 300e302, 301t MAB 33, 80 Mab therapies See Monoclonal humanized antibody therapies (Mab therapies) Macro-complexes, 167 Macro-enzymes, 75e76 Macroanalytes, 75e76 Macroprolactin, 173e174 Magnesium assays, 127 electrolyte analysis, 116, 119 Major histocompatibility complex (MHC), 202e203 MALDI See Matrix-assisted laser desorption (MALDI) MALDI-TOF See Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) Malignancies heparin-like anticoagulants, 395 Malignant disorders, 389e390 Mammalian target of rapamycin (mTOR), 225e226 Manchurian Fungus tea See Kombucha Tea Manchurian Mushroom tea See Kombucha Tea Mandrake, 302 MAPK See Mitogen activated protein kinase (MAPK) Marijuana metabolite, 251e252 Mass spectrometer and library searching, 268e269 methods, 263 Mass spectrometry (MS), 165, 176, 219e221, 233, 257 Mass spectroscopy See Mass spectrometry (MS) Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF), 380 Matrix-assisted laser desorption (MALDI), 268 Maximum reaction velocity (Vmax), 278 bk-MBDB, 259te260t MCH See Mean corpuscular hemoglobin (MCH) MCHC See Mean corpuscular hemoglobin concentration (MCHC) 483 MCV See Mean corpuscular volume (MCV) MDA See 3,4Methylenedioxyamphetamine (MDA) MDEA See Methylenedioxyethylamphetamine (MDEA) MDMA See 3,4Methylenedioxymethamphetamine (MDMA) bk-MDMA, 259te260t MDPV See 4Methylenedioxypyrovalerone (MDPV) MDRD See Modified Diet of Renal Disease (MDRD) Mean corpuscular hemoglobin (MCH), 158, 387 Mean corpuscular hemoglobin concentration (MCHC), 387 Mean corpuscular volume (MCV), 38e39, 158, 287, 387 errors in MCV and related measurements, 388 Medications, 235 interference from over counter and prescription, 236 Medullary thyroid carcinoma (MTC), 176 MEIA See Microparticle enzyme immunoassay (MEIA) MEIAtacrolimus (IMx), 227 Meigs’ syndrome, 197 Melanin, 265, 341e342 “Mellanby Effect”, 272 Melt analysis, 350 Melt temperature (TM), 350 Menopausal period and clinical laboratory test results, 47 Mentha pulegium (Pennyroyal), 300 Mephedrone, 259te260t MEPS See Micro-extraction by packed sorbent (MEPS) Messenger ribonucleic acid (mRNA), 360 Metabolitem-chlorophenylpiperazine (m-CPP), 236 Metabolites, 263e264 Methadone, 236, 250, 453 screening, 238 Methamfepramone, 259te260t Methamphetamine, 234e235, 247 Methanol, 467t poisoning, 466 Methcathinone, 259te260t Methedrone, 259te260t Methemoglobin, 59e60 Methicillin-resistant Staphylococcus aureus (MRSA), 454 Methotrexate, 216 4-Methyl pyrazole, 279 N-Methyl-N-t-butyldimethylsilyl trifluoroacetamide (MTBSTFA), 245e247 Methylene blue, 442 484 3,4-Methylenedioxy-N-methylcathinone, 259te260t 3,4-Methylenedioxyamphetamine (MDA), 234, 246 Methylenedioxyethylamphetamine (MDEA), 246 3,4-Methylenedioxymethamphetamine (MDMA), 234, 246, 258e259 4-Methylenedioxypyrovalerone (MDPV), 258e259, 259te260t 4-Methylmethcathinone (4-MMC), 259te260t Methylone, 259te260t Methylthiotetrazolium (MTT), 276 N-Methyltrimethylsilyltrifluoroacetamide (MSTFA), 245e246 Methysticin, 298 mf agglutination See Mixed-field agglutination (mf agglutination) MGUS See Monoclonal gammopathy of undetermined significance (MGUS) MHC See Major histocompatibility complex (MHC) MIC See Minimal inhibitory concentration (MIC) Micro-extraction by packed sorbent (MEPS), 266 Microalbuminuria, urinary albumin measurements to detecting, 142e143 Microarrays, 340 b2 Microglobulin (B2M), 202e203 Microparticle enhanced immunoassay See Microparticle enzyme immunoassay (MEIA) Microparticle enzyme immunoassay (MEIA), 218, 220 Midazolam (Versed), 252 pharmacokinetics, 296 Mineralocorticoid receptor antagonists, 177e178 Minimal inhibitory concentration (MIC), 380 Misidentification errors, specimens and clinical laboratory tests, 37e40 Mistletoe, 301t Mitochondrial FAO, 372e373 Mitogen activated protein kinase (MAPK), 353e354 Mixed technology, 462t Mixed-field agglutination (mf agglutination), 428e429 4-MMC See 4-Methylmethcathinone (4-MMC) Modification of Diet in Kidney Disease See Modified Diet of Renal Disease (MDRD) Modified Diet of Renal Disease (MDRD), 54e55, 103e105 limitations, 105e106 Molecular diagnostic analyses, error sources in amplification methods amplification inhibitors, 340e341 commonly encountered inhibitors and sources, 341e342 INDEX inhibition mechanisms, 341 monitoring for amplification inhibition, 342 PCR, 340 SDA, 340 strategies to prevents inhibition, 342 TMA, 340 causes of false positive and false negative results contamination, 344 false negative result of PCR testing for N meningitidis, 343e344 mispriming/cross reactivity of primers and probes, 344 sequence mismatch between primer and target DNA, 343e344 molecular methods amplification methods, 340e342 hybridization methods, 339e340 microarrays, 340 nucleotide sequencing, 342e343 pre-analytical issues, 337e339 nucleic acid extraction, 339 specimen assessment, 338 specimen collection, 337e338 specimen storage and transport, 338 quality management, 344e345 Molecular diagnostics, 337 Molecular technologies, 349 Molecular testing, 349 applications, 353e358 BCR/Abl, 355e356 HLA 5701, 357 HLA-B*15:02, 357e358 host factors influencing response to infectious disease, 357 KIT, 356e357 KRAS, 353e355 targeted therapies for tumor/somatic variant detection, 353 case studies, 361 genes in, 354t method description, 349e353 multi-variant panels, 350e351 sequencing, 351e353 targeted single variant detection, 349e350 pharmacogenetics of metabolic enzymes, 358e360 precision medicine and pediatrics, 360e361 Momordica charantia (bitter melon), 303, 303t 6-Monoacetyl morphine (6-MAM) See 6-acetylmorphine (6-AM) Monoamine alkaloid, 258e259 Monoclonal antibodies, polyclonal antibodies vs., 71 Monoclonal bands, 329 Monoclonal gammopathy, 329e331 Monoclonal gammopathy of undetermined significance (MGUS), 331 Monoclonal humanized antibody therapies (Mab therapies), 410e413 Monoclonal protein (M protein), 329, 331 detection, 329e331 Morphine, 236, 239, 249 Mouse monoclonal antibodies, 167, 167t MPA See Mycophenolic acid (MPA) MPA-glucuronide (MPAG), 226 MRM See Multiple reaction monitoring (MRM) mRNA See Messenger ribonucleic acid (mRNA) MRSA See Methicillin-resistant Staphylococcus aureus (MRSA) MS See Mass spectrometry (MS); Multiple sclerosis (MS) MSTFA See N-Methyltrimethyl silyltrifluoroacetamide (MSTFA) MTBSTFA See N-Methyl-N-tbutyldimethylsilyl trifluoroacetamide (MTBSTFA) MTC See Medullary thyroid carcinoma (MTC) mTOR See Mammalian target of rapamycin (mTOR) MTT See Methylthiotetrazolium (MTT) Multi-variant panels, 350e351 Multiple reaction monitoring (MRM), 220, 267e268, 369, 372e373 Multiple sclerosis (MS), 87e88 Multiplexed POC assays, 454 Multiplexing, 72 Mycobacteria tuberculosis, 454 Mycophenolate mofetil, 225e226 Mycophenolic acid (MPA), 225e226 Myeloblasts, 403e404 Myeloma, 409 Myocardial infarction, 151 N NAD+ See Nicotinamide adenine dinucleotide (NAD+) Nanodrop, 339 NaOH See Sodium hydroxide (NaOH) NAPA See N-Acetylprocainamide (NAPA) Naphylopyrovalerone, 259te260t Naphyrone, 259te260t NASBA See Nucleic acid sequence based amplification (NASBA) National Children’s Health Study (NCS), 46 National Committee for Clinical Laboratory Standards (NCCLS), 396 National Comprehensive Cancer Network (NCCN), 200 National Forensic Laboratory Information System (NFLIS), 259e261 National Glycohemoglobin Standardization Program (NGSP), 454 National Health and Safety Network (NHSN), 439, 444 National Institute on Alcohol Abuse and Alcoholism (NIAAA), 271 485 INDEX National Laboratory Certification Program (NLCP), 251 National Survey on Drug Use and Health (NSDUH), 271 Natural Medicine Comprehensive Database, 295 NCCLS See National Committee for Clinical Laboratory Standards (NCCLS) NCCN See National Comprehensive Cancer Network (NCCN) NCS See National Children’s Health Study (NCS) Near-patient testing See Point-of-care testing (POC testing) Negative interference of biotin, 83e84 Neisseria meningitidis, PCR testing false negative result for, 343e344 Neoplasia, 391 Nephelometric immunoassays, 70 NETs See Neutrophil extracellular traps (NETs) Neuron Specific enolase, 207 Neutral buffered formalin, 338 Neutrophil aggregation, 388e389 Neutrophil extracellular traps (NETs), 404 New psychoactive substances (NPS), 257 abuse, 257e259 in biological matrix, 264e266 confirmation of NPS, 267e269 mass spectrometers and library searching, 268e269 immunoassays, 266e267 Newborn meconiumdrug screening, 243e244 Newer urine biomarkers of prostate cancer, 196 Next-generation sequencing (NGS), 342e343, 349, 353 incorrect zygosity call for variant detection, 343 NFLIS See National Forensic Laboratory Information System (NFLIS) NGS See Next-generation sequencing (NGS) NGSP See National Glycohemoglobin Standardization Program (NGSP) NHSN See National Health and Safety Network (NHSN) NIAAA See National Institute on Alcohol Abuse and Alcoholism (NIAAA) Nicotinamide adenine dinucleotide (NAD+), 109 Nicotinamide adenine dinucleotide reduced form (NADH), 275e276 4-Nitrophenyl phosphate, 147 NLCP See National Laboratory Certification Program (NLCP) Non-beverage ethanol, 283 Non-competitive immunoassays, 167 Non-creatinine chromogens, 106 Non-hyperinsulinic hypoglycemia, 113 Non-seminomatous germ cell tumors (NSGCTs), 198, 205 Non-ST-elevation AMI (NSTEMI), 152 Non-waived devices, 456 Noncognitive errors, Nonfasting lipid profiles, 134e135 Noni juice, 49 Nopal, 303, 303t Nortriptyline, 227 Nova StatSensor, 108 Novel psychoactive substances (NPSs), 240 NPS See New psychoactive substances (NPS) NPSs See Novel psychoactive substances (NPSs) NRBC See Nucleated red cells (NRBC) NSDUH See National Survey on Drug Use and Health (NSDUH) NSGCTs See Non-seminomatous germ cell tumors (NSGCTs) NSTEMI See Non-ST-elevation AMI (NSTEMI) NT-pro-BNP, 155e156 Nucleases, 339 Nucleated red cells (NRBC), 388 Nucleic acid sequence based amplification (NASBA), 340 Nucleic acids, 337 See also Molecular diagnostics extraction, 339, 342 hybridization, 339 Nucleotide sequencing NGS, 342e343 Sanger sequencing, 342 Nusinersen See SPINRAZA Nutraceuticals effect, on clinical laboratory test results, 51 O O2Hb See Oxyhemoglobin (O2Hb) OCBQ See Office of Compliance and Biologics Quality (OCBQ) Ocfentanil, 259 Octagam, 116 OFD See Order of draw (OFD) Office of Compliance and Biologics Quality (OCBQ), 439 Ofloxacin, 237 OG See Osmole gap (OG) 25-OHD See 25-Hydroxyvitamin D (25-OHD) Oligoclonal bands, 331 On-site testing See Point-of-care testing (POC testing) Onshido, 300e301 OPA See Ortho-phthalaldehyde (OPA) Opiates, 236e237, 248 screening assays, 237e238 Opioids, 236e237, 248e251 codeine, 249e250 heroin, 249 hydrocodone, 250 hydromorphone, 250 interpretation of opioid results, 250e251 methadone, 250 morphine, 249 oxycodone, 250 oxymorphone, 250 Oral fluid, 262, 266 Order of draw (OFD), 19 for BCT, 19e21, 20t Organic acid disorders, 372e373, 373t Oriental weight loss products, 300e301 Ortho Clinical Diagnostics Vitros assays, 84 Ortho Vitros amylase slide, 148e149 Ortho Vitros dry chemistry method, 110 Ortho-phthalaldehyde (OPA), 369 OSM See Osmolality (OSM) OSMc See Calculated osmolality (OSMc) Osmolality (OSM), 285 Osmole gap (OG), 285e286 Osmotic fragility test, 391 Ostwald solubility coefficient See Blood/ breath partition ratio OTC See Over-the-counter (OTC) Ovarian cancer, 196 emerging biomarkers in diagnosis, 197e198 Over-the-counter (OTC), 246 Oxalate, 30 Oxazepam (Serax), 252 Oxazepam-glucuronide, 239 Oxidase ethanol methods, 279e280 2-Oxoglutarate, 143 Oxycodone, 236, 250 screening, 238e239 OxyElite Pro, 296e297 OxyELITE Pro, 296e297, 301t Oxygen parameters, 129e130 Oxygen-sensitive electrode, 101 Oxyhemoglobin (O2Hb), 130 Oxymorphone, 250 P P5P See Pyridoxal-5’-phosphate (P5P) PACU See Post-anesthesia care unit (PACU) Pancreatic lipase, 147e148 Pancreatic polypeptide, 181 Panhypogammaglobulinemia, 330 Panitumumab, 353e354 Paper chromatography, 452e453 Paper-based vertical flow microarray, 454 Papillary and follicular carcinomas, 175 PAPP-A See Pregnancy-associated polypeptide-A (PAPP-A) Paramagnetic particles (PMP), 70e71 Paraprotein See Monoclonal protein (M protein) Paraproteins, 408e410, 409f Parathyroid hormone (PTH), 165, 178e179 assays for 25-OHD, 179 Paroxysmal nocturnal hemoglobinuria (PNH), 60 Particle-enhanced turbidimetric inhibition immunoassay (PETINIA), 224e225 “Patient first” approach, 383 486 Patient preparation, for laboratory test results body posture, 12 fasting, 12 overview, 12 pCO2 See Pressure of carbon dioxide (pCO2) PCOS See Polycystic ovarian syndrome (PCOS) PCP See L-Phenylcyclohexylpiperidine (PCP) PCR See Polymerase chain reaction (PCR) Pediatrics, precision medicine and, 360e361 Pefloxacin, 237 PEG See Polyethylene glycol (PEG) Pennyroyal, 301t, 302 Pennyroyal See Mentha pulegium (Pennyroyal) Pentafluoropropionic acid anhydride (PFPA), 245e247 PEP See Phosphoenolpyruvate (PEP) Peppermint, 295 Percent [-2]proPSA, 195 Perineal trauma, 194 Persistent low levels of hCG, 203e204 Pesticides, 313 PEth See Phosphatidylethanol (PEth) PETINIA See Particle-enhanced turbidimetric inhibition immunoassay (PETINIA) PFA-100/200, 397 PFPA See Pentafluoropropionic acid anhydride (PFPA) PGx See Pharmacogenomics (PGx) Ph1 chromosome See Philadelphia chromosome (Ph1 chromosome) Phantom hCG, 204 Pharmacodynamics, 217 of ethanol, 272e273 Pharmacogenetics of metabolic enzymes, 358e360 CYP2D6 enzyme, 358e359 hemostasis, 359e360 testing for targeted therapies, 349 Pharmacogenomics (PGx), 350 Pharmacokinetics, 263 of ethanol, 273e275 select bodily fluids amenable to ethanol determination, 274t factors, 215e216 of NPS, 261e262 Pharmacological effects, 243 Phe-Pro-Argchloromethylketone (PPACK), 165e166 Phencyclidine, 252 Phenobarbital, 216 L-Phenylcyclohexylpiperidine (PCP), 252 Phenytoin, 216, 224e225 analytical variables, 225 case example, 225 pre-analytical variables, 225 PHI See Prostate Health Index (PHI) Philadelphia chromosome (Ph1 chromosome), 355 INDEX Phlebotomy, 165 Phosphate, 29, 121e122, 124 assays, 127e128 Phosphatidylethanol (PEth), 284e287 Phosphoenolpyruvate (PEP), 127 Phosphoinositol-3 kinase (PI3K), 353e354 Piper methysticum, 298 Piperazines, 257 Pituitary-gonadal axis, 46 Plantago ovata (Psyllium), 303 Plasma, 72 components, 13te14t serum vs., 12e13 for clinical laboratory analysis, 12e15 specimens, 15 water with indirect methods, 124e126 Plasma cells, 410 Plasma renin activity (PRA), 177 Plasma separator tubes (PSTs), 34e35 re-centrifugation, 34, 35t Plasma water fraction (PWF), 124 Plastic tubes, 16 Platelet (PLT), 441e442 agglutination, 390 aggregates, 408, 408f aggregation testing, 397 antagonists, 359e360 errors in platelet count, 389 satellitism, 390 Platelet neutralization procedure (PNP), 397e398 Platelet-rich plasma (PRP), 397 PLT See Platelet (PLT) PMP See Paramagnetic particles (PMP) Pneumatic tube systems, 29e30 PNH See Paroxysmal nocturnal hemoglobinuria (PNH) PNP See Platelet neutralization procedure (PNP) POC testing devices, 451, 455 design, 451 guidelines for using, 455e456 methodological issues, 452e455 blood gas, 455 cardiac markers, 454 coagulation meters, 455 diabetes markers, 454 drugs of abuse, 452e454 glucose, 452 ID, 454 metabolites, 452 multiplexed POC assays, 454 pregnancy tests, 454 Point-of-care (POC) See also POC testing devices assays, 72, 113 identification systems, 4e5 meters, 13e14 Pokeroot, 302 Poly MAB 33, 80 Polyagglutination, 428e429 Polyclonal antibodies, monoclonal antibodies vs., 71 Polycystic ovarian syndrome (PCOS), 173 Polyethylene glycol (PEG), 70, 167, 174, 282, 429 Polymerase chain reaction (PCR), 325e326, 338, 340, 349e350 false negative result for N meningitidis, 343e344 inhibitors, 341t Polymorphic variants, 358 Pores, 116e118 Positive interference of biotin, 83e84 Post-analytical errors, 3, Post-analytical errors in microbiology laboratory, 380e381 reporting, 380e381 Post-anesthesia care unit (PACU), 445 Post-transfusion purpura, 443 Postmenopausal woman, 203e204 Potassium EDTA, 18 Potassium hydroxide (KOH), 245 Potassium oxalate, 19 Potassium permanganate, 461 Potentiometry, 127 PPACK See Phe-ProArgchloromethylketone (PPACK) PPAR a agonists See Proliferator-activated receptor a agonists (PPAR a agonists) PQQ See Pyrrol-quinoline quinone (PQQ) PRA See Plasma renin activity (PRA) Prazepam (Centrax), 252 Pre-analytical errors, in microbiology laboratory, 377e380 Prealbumin, 50 Precision medicine and pediatrics, 360e361 Pregnancy tests, 454 Pregnancy-associated polypeptide-A (PAPP-A), 181e182 Preservatives in urine, 72 Pressure of carbon dioxide (pCO2), 124 Prickly pear cactus See Nopal Primary sclerosing cholangitis (PSC), 200 Prl See Prolactin (Prl) Probe chemistries, 350 Procalcitonin, 454 Proficiency testing (PT), 382 Prolactin (Prl), 166e167, 173e174 Proliferator-activated receptor a agonists (PPAR a agonists), 143e144 Promazine, 238 proPSA See PSA produced as proantigen (proPSA) Propyl alcohol, 467t Prostate cancer, 193e194 Prostate Health Index (PHI), 195 Prostate specific antigen (PSA), 48, 180, 191e196 BPH, 193 cPSA, 195 elevated PSA in prostate cancer and conditions, 193e194 expression and processing, 193 false positive and unexpected PSA results, 195e196 487 INDEX newer urine biomarkers of prostate cancer, 196 percent [-2]proPSA, 195 serum free and bound, 194e195 testing, 194 Prostatitis, 193e194 Protein, total, 141e143 Prothrombin time (PT), 18, 395 errors in measurement, 395 Protoon-cogene Neu See Human epidermal growth factor receptor (HER 2) Prozone effect, 75, 81 PRP See Platelet-rich plasma (PRP) PSA See Prostate specific antigen (PSA) PSA produced as proantigen (proPSA), 193 PSC See Primary sclerosing cholangitis (PSC) Pseudoagglutination, 432 Pseudodeficiency, 374 Pseudoephedrine, 236 Pseudohyponatremia, 63, 122e123, 123t Pseudomonas aeruginosa, 380 Pseudothrombocytopenia, 390 PSTs See Plasma separator tubes (PSTs) Psyllium See Plantago ovata (Psyllium) PT See Proficiency testing (PT); Prothrombin time (PT) PTH See Parathyroid hormone (PTH) PTT measurement, errors in, 395 Pulse oxymetry, 130 Purification, 339 PWF See Plasma water fraction (PWF) Pyridoxal-5’-phosphate (P5P), 143 Pyrogram, 352e353 Pyrosequencing, 351e353, 355 Pyrovalerone, 259te260t Pyrrol-quinoline quinone (PQQ), 115 Q Q-wave AMI, 152 QA See Quality assurance (QA) QC See Quality control (QC) qPCR See Quantitative PCR (qPCR) qRT-PCR See Quantitative RT-PCR (qRT-PCR) Qualitative assays, QC for, 345 Quality See also Total quality management (TQM) defined, 6e7 improvement, 382e383 of laboratory operations, 6e9 management, 344e345 Quality assurance (QA), 6e7, 366e368, 440 Quality control (QC), 6e7, 344e345, 366e368, 382e383 for qualitative assays, 345 for quantitative assays, 345 Quantitative assays, QC for, 345 Quantitative PCR (qPCR), 341, 350 Quantitative RT-PCR (qRT-PCR), 355e356 Quazepam (Doral), 252 Qubit, 339 Quenching, 416 Quetiapine, 238 Quinolone antibiotics, 237 R Rabbit erythrocyte stroma (RES), 436 Rabbit erythrocyte stromal test (RESt), 435 Radiative Energy Attenuation (REA), 276 Radio frequency identification (RFID), 39 Radioimmunoassay (RIA), 70e71, 173 Radioimmunoassays, 221e222 Radiometer ABL800, 108 Random error (RE), 7, 7f Randox Biochip, 454 Randox Laboratories’ Biochip arrays, 72 Ranitidine, 236 Rapid 5-min Clot Serum Tube (RST), 19 RBC See Red blood cell (RBC) RCA See Root cause analysis (RCA) RCF See Relative centrifugal force (RCF) RCV See Reference change value (RCV) RDW See Red cell distribution width (RDW) RE See Random error (RE) REA See Radiative Energy Attenuation (REA) Real time DNA sequencing, 352 Real time PCR, 340, 350 Receiver operator characteristic (ROC), 194 Recipient isohemagglutinins, 440 Recognition and prevention of errors, 168 Recombinant immunoblot assay (RIBA), 327 Red blood cell (RBC), 321, 425, 439 agglutination, 428e429 Ags, 426 alloimmunization, 441 count, 387 errors in, 388 phenotype, 427 Red cell distribution width (RDW), 387 Reference change value (RCV), 7, 8t Relative centrifugal force (RCF), 34 RES See Rabbit erythrocyte stroma (RES) Respiratory viral assays, 337 Respiratory viruses, 378 RESt See Rabbit erythrocyte stromal test (RESt) Resveratrol, 303 Reverse transcriptase-PCR (RT-PCR), 355e356 Revolutions per minute (RPM), 34 RF See Rheumatoid factor (RF) RFID See Radio frequency identification (RFID) Rhabdomyolysis, 302 Rhesus blood group D antigen (RhD), 39 typing, 426 Rheumatoid factor (RF), 75e77, 167e168, 199, 396e397 RIA See Radioimmunoassay (RIA) RIBA See Recombinant immunoblot assay (RIBA) Rifampicin, 237 RIN See RNA integrity number (RIN) Risk of ovarian malignancy algorithm (ROMA), 197 Risperidone, 238 Rituximab, 410e411 RNA, 338 RNA integrity number (RIN), 339 ROC See Receiver operator characteristic (ROC) Roche Elecsys immunoassays, 84 Roche KIMS methadone assay, 238 ROMA See Risk of ovarian malignancy algorithm (ROMA) Room temperature (RT), 28e29 plastic syringe transportation at, 32 Root cause analysis (RCA), 5e6, 420 Rotational TEG (ROTEG), 397 ROTEG See Rotational TEG (ROTEG) ROTEM See Rotational TEG (ROTEG) Rouleaux phenomenon, 432 Routine testing, 366 Royal jelly, 51 RPM See Revolutions per minute (RPM) RST See Rapid 5-min Clot Serum Tube (RST) RT See Room temperature (RT) RT-PCR See Reverse transcriptase-PCR (RT-PCR) Russian tarragon See Artemisia dracunculus (Russian tarragon) S Salicin, 302 SAMHSA See Substance abuse and mental health services administration (SAMHSA) Sandwich immunoassays, 69e70 Sanger sequencing, 342, 351, 354e355 Sarcosine, 108, 368e369 Sassafras, 302 SCCAs See Squamous cell carcinoma antigens (SCCAs) Scorpion primers, 355 SCr See Serum creatinine (SCr) SCV See Significant change value (SCV) SD See Standard deviation (SD) SDA See Strand-displacement amplification (SDA) SE See Systematic error (SE) Seaweed See Kelp Secondary ion, 263 Selected ion monitoring (SIM), 220 Semi-synthetic alkaloids, 248 Semiconductor, 462t Senna, 302 Septic transfusion reaction, 442e443 Sequencing, 351e353 dideoxy, 352e353 DNA, 351 nucleotide, 342e343 real time DNA, 352 Sanger, 342, 351, 354e355 whole exome, 343 Serologic RBC phenotype, 425 Serology testing See Immunology and serology testing 488 Serum, 72 CEA concentration, 199e200 components, 14t epididymis protein-4, 197 free PSA, 194e195 osmolality, 285 plasma vs., 12e13 for clinical laboratory analysis, 12e15 protein, 218 specimens, 15 Serum creatinine (SCr), 103e105 Serum ethanol, 284 concentration, 272t Serum glutamate-oxaloacetate transaminase (SGOT) See Aspartate aminotransferase (AST) Serum glutamate-pyruvate transaminase (SGPT) See Alanine aminotransferase (AST) Serum protein electrophoresis (SPEP), 329 See also Monoclonal protein (M protein) negative, 330e331 problems encountered in, 329t Serum separator gel tubes (SST), 17e18, 34 Sex hormone binding globulin (SHBG), 168 Sex steroid measurements, 180 SHBG See Sex hormone binding globulin (SHBG) Sho-Saiko-to, 300e301 Shou-Wu-Pian, 300e301 SI See Staining index (SI) Sialylated Lewis See Carbohydrate antigen 19e9 (CA-19e9) Sickle cell disease (HbSS), 324 Sickle cell trait (HbAS), 324 Siemens Healthineers, 84 Significant change value (SCV), Silica binding method, 339 SIM See Selected ion monitoring (SIM) Single nucleotide resolution, 351 Single nucleotide variants (SNVs), 353 Sirolimus, 225 Six Sigma, 5e6 SJS See Steven-Johnson syndrome (SJS) Skin puncture for blood specimen collection, 21e22 Skullcap, 301t SMA See Spinal muscular atrophy (SMA) SMN See Survival motor neuron (SMN) Smoldering myeloma, 331 SNVs See Single nucleotide variants (SNVs) Sodium hydroxide (NaOH), 245 Solid phase extraction (SPE), 241, 245, 263 Soluble transferrin receptor (sTfR), 52e53, 159 Somatic variants, 353 Somatostatin See Somatotropin releaseinhibitory hormone (SRIH) Somatotropin release-inhibitory hormone (SRIH), 170, 181 INDEX SOPs See Standard operating procedures (SOPs) Soy, 295 SPE See Solid phase extraction (SPE) Specialized testing, 366 Specimen validity tests (SVT), 244 Specimens adulteration, 234 blood, 13e15 components of, 14t centrifugation of, 33e35 chilled, 31 contamination, 19 cross-contamination, and clinical laboratories results, 37 dilution, 234 in immunoassays, 72 misidentification, and laboratory testing, 37e40 overview, 12e15 transportation, 27e33 temperature effects during, 30e31 time, 27e30 urine, 23e24 validity testing, 253e254 Spectrophotometer, 339 SPEP See Serum protein electrophoresis (SPEP) Spermicide nonoxynol-9, 196 Spinal muscular atrophy (SMA), 360e361 SPINRAZA, 360 Spray-dried potassium EDTA, 18 Spurious leukcopenia, 388, 390 Spurious leukocytosis, 391 Spurious leukopenia, 388 Squamous cell carcinoma antigens (SCCAs), 207 SRIH See Somatotropin release-inhibitory hormone (SRIH) SSA/Ro antigen, 332 SST See Serum separator gel tubes (SST) ST-elevation AMI (STEMI), 152 St John’s wort, 295e296, 306 drug interactions with, 309te310t interaction with various drugs, 306e309 Stability, 263 Staining index (SI), 415 Standard deviation (SD), 6e7 Standard operating procedures (SOPs), 439 Standards for Reporting Diagnostic Accuracy (STARD), 287e288 Staphylococcus aureus, 382 Star alleles See Haplotypes STARD See Standards for Reporting Diagnostic Accuracy (STARD) STEMI See ST-elevation AMI (STEMI) “Step ladder” pattern, 330 Sterile body fluids, 337e338 Steven-Johnson syndrome (SJS), 357e358 sTfR See Soluble transferrin receptor (sTfR) Stoppers lubricants, 16e17 Strand-displacement amplification (SDA), 340 Streptavidin, 83 Streptomyces avidinii, 83 Structural variants (SVs), 353 Substance abuse and mental health services administration (SAMHSA), 233, 244 Substituted specimen, 253e254 Substrate concentration, 278e279 Suprapubic aspiration, 23e24 Surfactants, 16 Survival motor neuron (SMN), 360 SVs See Structural variants (SVs) SVT See Specimen validity tests (SVT) Sympathomimetic amines, 246 Sympathomimetics, 234 Symphytum officinale (Comfrey), 299, 301t, 302 Synthetic cannabinoids, 257e259, 258f, 265 Synthetic cathinones, 257e259, 259f, 259te260t System errors, Systematic error (SE), 7, 7f Syto-16, 402 T T-APC synapsing, 407 T&S See Type and screen (T&S) TA-GVHD See Transfusion-associated graft versus host disease (TAGVHD) TAAE See Total acceptable analytical error (TAAE) TACO See Transfusion associated circulatory overload (TACO) Tacrolimus, 225 TAE See Total analytical error (TAE) Tandem dyes, 416e418, 417t Tapentadol, 238 TaqMan OpenArray PGx, 350 TaqMan technology, 350 Target cells, 388 Targeted pyrosequencing, 352e353 Targeted single variant detection, 349e350 Targeted therapies, 349 for tumor/somatic variant detection, 353 TAT See Turnaround time (TAT) TBG See Thyroxine-binding globulin (TBG) TBH See Tetrabutylammonium hydroxide (TBH) TBPA See Thyroxine-binding prealbumin (TBPA) TC See Total cholesterol (TC) TCAs See Tricyclic antidepressants (TCAs) TDM See Therapeutic drug management (TDM) TEG See Thromboelastography (TEG) Tegretol, 224 “Tekumut”, 305 Temazepam (Restoril), 252 Temperature and specimens transportation, 30e31 TEN See Toxic epidermal necrolysis (TEN) Testosterone, 12, 165, 273, 388 INDEX Tests, clinical laboratory cross-contamination of specimens and, 37 effects of centrifugation on, 33e35 patient preparation for See Patient preparation, for laboratory test results results of adults and, 46 aging and, 45e48 children and, 46 circadian rhythms, 12 diet and, 49e52 ethnicity/race, 54 exercise and, 52e53, 54t gender differences and, 48e49 geriatric population and, 48 hemolysis and, 58e63 icterus and, 64e65 lipemia and, 63e64 menopausal period and, 47 newborns, 46 nutraceuticals and, 51 specimen misidentification and, 37e40 storage conditions and, 36 Tetrabutylammonium hydroxide (TBH), 245e246 Tetrahydrocannabinol-9-carboxylic acid (THCA), 251e252 Teucrium chamaedrys (Germander), 299, 301t TFAA See Trifluoroacetic anhydride (TFAA) TG See Triglycerides (TG) TGAs See Thyroglobulin autoantibodies (TGAs) THAM See Tris(hydroxymethyl) aminomethane (THAM) THC See Delta-9-tetrahydrocannabinol (THC) THCA See Tetrahydrocannabinol-9carboxylic acid (THCA) The Joint Commission (TJC), 37e38 Therapeutic antibodies, 75e76, 78 Therapeutic drug management (TDM), 69, 215 algorithm for evaluating, 219f analytical interferences, 217e219, 218t mechanisms, 219e221 antidepressants and mood stabilizer, 227e229, 228t lithium, 228e229 TCAs, 227e228 carbamazepine, 224 analytical variables, 224 drug-drug interactions, 224 pre-analytical variables, 224 chromatography, 220e221 digoxin aldosterone antagonists, 223 analytical variables, 221 anti-digoxin immune fragments, 223 cardiac glycosides, 223 case example, 224 DLIF, 222e223 herbal medicines, 223e224 interferences with digoxin immunoassays, 222t measurement, 221e224 metabolites, 221e222 pre-analytical variables, 221 drug stability and, 215e216 endogenous interferences, 218 exogenous interferences, 218 immunosuppressants, 225e227, 226t analytical variables, 226e227 case example, 227 drug metabolites, 226 endogenous interfering substances, 227 pre-analytical variables, 226 interferences, 221e224 lithium, 228e229 analytical variables, 228e229 pre-analytical variables, 228 mass spectrometry, 219e221 phenytoin, 224e225 analytical variables, 225 case example, 225 pre-analytical variables, 225 pre-analytical factors affecting drug levels, 215e217, 216f in pregnant women, 217 TCAs, 227e228 analytical variables, 227e228 case example, 228 pre-analytical variables, 227 Therapeutic drug monitoring See Therapeutic drug management (TDM) Thermo Fisher Scientific TaqMan OpenArray, 358 Third generation tests, 324 Thixotropic gel, 30 Thixotropic polymeric gels, 282 Thrombin, 19 Thrombin time measurement (TT), 395 errors in, 395e397 dilution or contamination with anticoagulants, 396 fibrinolysis products and rheumatoid factor, 396e397 incorrectly filled tubes, 396 PFA-100/200, 397 traumatic phlebotomy, 396 Thrombocytopenia, 397 Thromboelastography (TEG), 395, 397e398 case study, 398 challenges in anticoagulants and lupus anticoagulant tests, 397e398 Thyroglobulin (Tg), 175e176 Thyroglobulin autoantibodies (TGAs), 176 Thyroid function immunoassays, 77 tests, 175e176 CT, 176 thyroglobulin, 175e176 Thyroid stimulating hormone (TSH), 52, 165, 167, 172e173 489 Thyrotropin, 165 Thyroxine-binding globulin (TBG), 168 Thyroxine-binding prealbumin (TBPA), 168 TIA See Turbidimetric immunoassay (TIA) TIBC See Total iron binding capacity (TIBC) Time-of-flight (TOF), 262, 268 Tissierella creatinini, 109 TJC See The Joint Commission (TJC) TMA See Transcription-mediated amplification (TMA) TMAH See Trimethylanilinium hydroxide (TMAH) TMCS See Trimethylchlorosilane (TMCS) TMPRSS2 See Transmembrane protease serine (TMPRSS2) TMS See Trimethylsilyl (TMS) TOF See Time-of-flight (TOF) Toluene, 467t TOOS See N-Ethyl-N-(2-hydroxy-3sulfopropyl)-m-toluidine (TOOS) Total acceptable analytical error (TAAE), Total analytical error (TAE), 7, 7f Total cholesterol (TC), 134 Total CO2, 127 Total iron binding capacity (TIBC), 156 Total quality management (TQM), 5e6 See also Quality Total testing process, 5e6 Tourniquet effect, 22 Toxic alcohols, 278, 287e288, 288t Toxic epidermal necrolysis (TEN), 357e358 TPC See N-Trifluoroacetyl-1-prolyl chloride (TPC) TQM See Total quality management (TQM) TRALI See Transfusion related acute lung injury (TRALI) Tramadol, 239 Transaminase levels, 146 Transcription-mediated amplification (TMA), 339e340 Transdermal alcohol sensors, 459 Transfusion, blood, 439 adverse effects of, 440e445 case study, 445 errors in, 439e440 Transfusion associated circulatory overload (TACO), 439, 443 Transfusion medicine tests, interferences in, 428 ABO/RhD typing, 425e427 antibody screen and extended panel, 426 Transfusion reaction allergic, 442 septic, 442e443 Transfusion related acute lung injury (TRALI), 439, 442e443 Transfusion-associated graft versus host disease (TA-GVHD), 439, 443e444 490 Transmembrane protease serine (TMPRSS2), 196 Transportation plastic syringe, at RT, 32 specimens, 27e33, 28te29t temperature effects during, 30e31 time, 27e30 Transrectal ultrasound (TRUS), 194 Transthyretin See Thyroxine-binding globulin (TBG) Transurethral resection of prostate (TURP), 193 Trastuzumab, 192 Traumatic phlebotomy, 396 Trazodone, 236 Triazolam (Halcion), 252 Tricyclic antidepressants (TCAs), 227e228 Trifluoroacetic anhydride (TFAA), 245e247 N-Trifluoroacetyl-1-prolyl chloride (TPC), 246e247 Triglycerides (TG), 134 gap, 288 and turbidity, 63 Triiodothyronine (TT3), 16, 48 Trimethylanilinium hydroxide (TMAH), 245e246 Trimethylchlorosilane (TMCS), 245e246, 369e371 Trimethylsilyl (TMS), 369e371 Triplet repeat disorders, 339e340 Tris(hydroxymethyl)aminomethane (THAM), 278 Troponin I Ultra assay, 84 Troponins, 151 TNNI1, TNNI2 and TNNI3, 151 TRUS See Transrectal ultrasound (TRUS) Tryptamines, 257 TSH See Thyroid stimulating hormone (TSH) TT See Thrombin time measurement (TT) TT3 See Triiodothyronine (TT3) Tumor markers, 208t AFP, 198e199 B2M, 202e203 CA 15e3, 205e206 CA 72e4, 207 CA-19e9, 201e202 CA-125, 196e198 CEA, 199e201 clinical application, 191e192, 192t detecting relapses, 192 diagnosis of cancer, 191e192 evaluating prognosis, 192 monitoring therapy, 192 screening and early detection of cancer, 191 frequently monitored tumor markers, 207 hCG, 203e205 hetrophilic antibody interference in tumor markers testing, 206e207 markers of breast cancer, 205e206 INDEX overview, 191 PSA, 193e196 BPH, 193 cPSA, 195 elevated PSA in prostate cancer and conditions, 193e194 expression and processing, 193 false positive and unexpected PSA results, 195e196 newer urine biomarkers of prostate cancer, 196 percent [-2]proPSA, 195 serum free and bound PSA, 194e195 testing, 194 Tumorigenesis, 191 Turbidimetric immunoassay (TIA), 70, 81 Turnaround time (TAT), 29e30, 381 TURP See Transurethral resection of prostate (TURP) Tussilago farfara (Coltsfoot), 299, 301t Type and screen (T&S), 425 U U.S Dried blood spots (DBS), 322 U.S Food and Drug Administration (FDA), 116, 295, 360, 378, 439 UFC See Urinary free cortisol (UFC) UGT See Uridine diphosphate glucuronyl transferase (UGT) UGT1A1 gene, 132 UHPLC See Ultra-high-performance liquid chromatography (UHPLC) UHPLC-MS/MS See Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) ULOL See Upper limit of linearity (ULOL) Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), 265 Ultra-high-performance liquid chromatography (UHPLC), 266 Ultradian rhythms, 12 Unexpected RBC antigen-like reactivity, 428e429 Unique molecular identifiers (UMIs), 343 United States Department of Defense, 460 United States of America (USA), 271 Upper limit of linearity (ULOL), 244 Uprizing, 296, 301t Urea analysis, 109e111 assay methods, 110e111 Urea Cycle Disorders Conference Group, 111e112 Urease, 110 Uric acid analysis, 112e113 analytical considerations, 112e113 Uridine diphosphate glucuronyl transferase (UGT), 253 Urinary excretion, 245, 250 Urinary free cortisol (UFC), 177 Urinary microalbumin, 452 Urine, 11, 233, 235t, 243, 264e265 electrophoresis, 330e331 ethanol result, 283 immunoassays, 72 preservatives in, 72 specimens, collection of, 23e24 clean catch specimen, 23 specimen labeling, 23 timing of, 23 USA See United States of America (USA) Usnic acid, 296e297, 301 V Valerian, 306 Valium See Diazepam Valproate, 371e372 Valproic acid, 216 Vanadium, 303 Vancomycin resistant S aureus (VRSA), 382 Vapor pressure dew point depression (VPD), 285 Vasoactive intestinal polypeptide (VIP), 18, 165e166, 181 VDBP See Vitamin D binding protein (VDBP) Venipuncture for blood specimen collection, 22 Verapamil, 238 Very low density lipoprotein cholesterol (VLDL-C), 52e53 Very low-density lipoprotein (VLDL), 49e50, 63e64, 134 VIP See Vasoactive intestinal polypeptide (VIP) Viral load monitoring, 337 Vitamin B, 168 Vitamin D binding protein (VDBP), 179 Vitamin K, 359 Vitros application, 276 Vitros dry chemistry method, 112 VKORC1 enzyme, 359e360 VLDL See Very low-density lipoprotein (VLDL) VLDL-C See Very low density lipoprotein cholesterol (VLDL-C) Volatile alcohols, 275 Volatile organic compounds, 466 VPD See Vapor pressure dew point depression (VPD) VRSA See Vancomycin resistant S aureus (VRSA) W WAA See Warm auto-Abs (WAA) Waived devices, 456 Warfarin, 455 interactions with, 310e311 warfarin-herb interactions, 311t Warm auto-Abs (WAA), 429 Warm ischemia time, 338 “Warmup protocol”, 413 WBC See White blood cell (WBC) 491 INDEX WBIT See Wrong blood in tube (WBIT) Western blot test, 325 Wharton’s jelly, 428e429 White blood cell (WBC), 331 count, 387 errors in, 388e389 WHO See World Health Organization (WHO) Whole blood, 12e15 analyzers, 108 components, 14t and lipemia visual detection, 63e64 storage of, 36 Whole exome sequencing, 343 Willow bark, 302 “Wolff-Chaikoff” effect, 305e306 World Health Organization (WHO), 271, 295, 298, 465 Wrong blood in tube (WBIT), 39, 427 X Xanthine, 112e113 XM testing See Crossmatch testing (XM testing) xTag, 350e351 Xylene, 467t Y Yangonin, 298 Yohimbe, 302 Yohimbine, 302 Z ZAP70, 406 Zexie, 300e301 Zhen Chu Cao, 300e301 “ZhenQi”, 304e305 Zinc protoporphyrin (ZPP), 313 Zinc protoporphyrin content (ZnPP), 160 Zwitterions, 321e322 ... review of the factors leading to errors in all the areas of clinical laboratory testing As such it will be of great value to all laboratory directors and trainees in laboratory medicine and the technical... percentages Bio TAAE, total allowable analytical error based on interindividual and intraindividual variation; CLIATAAE, total allowable analytical error based on Clinical Laboratory Improvement Act... 1.1 VARIATION, ERRORS, AND QUALITY IN THE CLINICAL LABORATORY Types of error in the clinical laboratory TABLE 1.1 Types of error in the clinical laboratory. dcont’d PRE-ANALYTICAL ANALYTICAL Test