Small Animal CLINICAL DIAGNOSIS LABORATORY METHODS by Small Animal CLINICAL DIAGNOSIS LABORATORY METHODS by FIFTH EDITION Michael D. Willard, DVM, MS, DACVIM Professor of Small Animal Medicine Department of Small Animal Medicine and Surgery College of Veterinary Medicine Texas A&M University College Station, Texas Harold Tvedten, DVM, PhD, DACVP, DECVCP Professor Emeritus Department of Pathobiology and Diagnostic Investigations College of Veterinary Medicine Michigan State University East Lansing, Michigan Department of Clinical Sciences Faculty of Veterinary Medicine Swedish University of Agricultural Sciences Uppsala, Sweden 3251 Riverport Lane St. Louis, Missouri 63043 SMALL ANIMAL CLINICAL DIAGNOSIS BY LABORATORY METHODS, FIFTH EDITION ISBN: 978-1437706574 Copyright © 2012, 2004, 1999, 1994, 1989 by Saunders, an imprint of Elsevier Inc. All rights reserved. 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Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted ISBN: 978-1437706574 Vice President: Linda Duncan Content Strategy Director: Penny Rudolph Content Development Specialist: Brandi Graham Publishing Services Manager: Julie Eddy Project Manager: Jan Waters Design: Teresa McBryan Working together to grow libraries in developing countries Printed in the United States of America www.elsevier.com | www.bookaid.org | www.sabre.org Last digit is the print number: 9 8 7 6 5 4 3 2 1 Contributors Jeanne A. Barsanti, DVM, MS, DACVIM Mark C. Johnson, DVM, DACVP (Clinical Josiah Meigs Distinguished Teaching Professor, Emeritas Pathology) Small Animal Internist, Emeritas Clinical Associate Professor Department of Small Animal Medicine and Surgery Department of Veterinary Pathobiology The University of Georgia Teaching Hospital College of Veterinary Medicine & Biomedical Sciences The University of Georgia Texas A&M University Athens, Georgia College Station, Texas Dawn Merton Boothe, DVM, MS, PhD, DACVIM, Ned F. Kuehn, DVM, MS, DACVIM DACVP Chief of Internal Medicine Services Professor Michigan Veterinary Specialists Department of Physiology and Pharmacology Southfield, Michigan College of Veterinary Medicine Director, Clinical Pharmacology Laboratory Michael R. Lappin, DVM, PhD, DACVIM Auburn University Professor Auburn, Alabama Department of Veterinary Clinical Sciences College of Veterinary Medicine and Biomedical Sciences Sharon A. Center, DVM, DACVIM Colorado State University Professor Fort Collins, Colorado Department of Veterinary Clinical Sciences College of Veterinary Medicine Gwendolyn J. Levine, DVM Cornell University Veterinary Clinical Associate Ithaca, New York Department of Pathology College of Veterinary Medicine & Biomedical Sciences Stephen P. DiBartola, DVM, DACVIM Texas A&M University Associate Dean for Administration and Curriculum College Station, Texas Professor of Medicine Department of Veterinary Clinical Sciences Jonathan M. Levine, DVM, DACVIM (Neurology) College of Veterinary Medicine Assistant Professor of Neurology/Neurosurgery The Ohio State University Department of Small Animal Clinical Sciences Columbus, Ohio College of Veterinary Medicine & Biomedical Sciences Texas A&M University Sonya G. Gordon, DVM, DVSc, DACVIM College Station, Texas Associate Professor Department of Small Animal Medicine and Surgery Richard W. Nelson, DVM, DACVIM College of Veterinary Medicine & Biomedical Sciences Professor of Internal Medicine Texas A&M University Department of Medicine and Epidemiology College Station, Texas School of Veterinary Medicine University of California Paula Martin Imerman, BS, MS, PhD Davis, California Clinician and Associate Scientist Department of Veterinary Diagnostic and Production Gary Osweiler, DVM, MS, PhD, DABVT Animal Medicine Professor College of Veterinary Medicine Department of Veterinary Diagnostic and Production Iowa State University Animal Medicine Ames, Iowa Veterinary Toxicologist Veterinary Diagnostic Laboratory Cheri A. Johnson, DVM, MS, DACVIM College of Veterinary Medicine Professor Iowa State University Department of Small Animal Clinical Sciences Ames, Iowa College of Veterinary Medicine Michigan State University East Lansing, Michigan v vi    Contributors Rose E. Raskin, DVM, PhD, DACVP David C. Twedt, DVM, DACVIM Professor of Veterinary Clinical Pathology Professor Department of Comparative Pathobiology Department of Veterinary Clinical Sciences School of Veterinary Medicine College of Veterinary Medicine and Biomedical Sciences Purdue University Colorado State University West Lafayette, Indiana Fort Collins, Colorado Jennifer S. Thomas, DVM, PhD, DACVP Douglas J. Weiss, DVM, PhD Associate Professor Professor Emeritus Department of Pathobiology and Diagnostic Department of Veterinary Biomedical Sciences Investigation College of Veterinary Medicine College of Veterinary Medicine University of Minnesota Michigan State University St. Paul, Minnesota East Lansing, Michigan Preface Our intent has been to help veterinarians and veterinary students appropriately select and accurately interpret laboratory tests in as simple, practical, and rapid a manner as possible. The popularity of the first and then subsequent editions has surprised and pleased us. Simple is good. With age one forgets the small details and remembers only the major principles that get one through the day. As with the first four editions, this fifth edition of Small Animal Clinical Diagnosis by Laboratory Methods is intended to present organized methods of answering commonly asked questions that reflect the problems frequently encountered with interpretation of laboratory test results. Most authors have updated their chapters as opposed to writing new ones with the idea that they could focus on making them as timely as possible. New authors have been added in some areas. We have attempted to make this text as current as possible, but this goal borders on impossible in a profession that is continually advancing. References and pathophysiology have been kept to a minimum because this text is designed to be user-friendly to both the busy clinician in the middle of a hectic day, as well as the student who is learning the art/science of problem solving. Michael D. Willard and Harold Tvedten vii Dedicated to my wife, Gladys, without whom I could not have done this, nor would I have cared to do it. Michael D. Willard Dedicated to the thousands of veterinary students and veterinarians, hundreds of medical technicians, and tens of clinical pathology residents with whom I have shared tens of thousands of discussions on diagnosis with laboratory methods over the last 40 years. It is for them and with them that it is fun to come to work each day. Speakers at veterinary meetings need not fear my questions, for they are only questions I ask myself each day. Harold Tvedten 1  General Laboratory Concepts Harold Tvedten and Jennifer S. Thomas TEST SELECTION AND ASKING THE context of the history, physical examination, and other RIGHT QUESTION diagnostic findings in a patient. Unexpected results are common and should stimulate the clinician to reevaluate Veterinarians have many choices regarding laboratory the provisional diagnosis and look for additional diseases testing. Important factors include availability of reference or consider possible causes for erroneous laboratory laboratory testing, reliability and ease of in-clinic testing, results. Trends over several days are often more informa- cost-effectiveness, accuracy, and turnaround time. One tive than test results on a single day. Typically, not all test must determine what tests to perform in-clinic and what results that “should be” abnormal in a disease situation tests to send out to a veterinary reference laboratory or to are abnormal in each affected patient. a local human laboratory. Recent improvements in the automation and ease of use of analyzers designed for NOTE: A reasonable level of skepticism about laboratory in-clinic use are changing what is acceptable. Correct results should be maintained. choices vary with the needs and patient population of each veterinary clinic. No one answer fits all situations. To get a specific and meaningful answer from labora- When interpreting laboratory tests, it is important to tory testing, the diagnostician must ask a specific and keep in mind that reference intervals include the results meaningful question and understand whether a particular expected in 95% of normal animals. Thus 5% of results laboratory test is likely to yield a useful answer. As an in normal animals (i.e., 1 of 20) are expected to be example, compare the likely outcome of asking the fol- outside the reference intervals. If a profile of 20 tests is lowing questions: “Is the animal anemic?” “What is wrong performed, only 36% of normal animals would have all with the animal?” A microhematocrit procedure (in addi- 20 results within the 95% confidence interval reference tion to knowledge of the animal’s hydration status) will values. Diagnosticians must expect some false-positive usually answer the first specific question, but a serum and false-negative test results. No tests are 100% sensitive chemistry profile, complete blood count (CBC), urinaly- and 100% specific for a disease. sis, and fecal examination may or may not answer the second vague, nonspecific question. A clinician should NOTE: Only slightly more than one third of normal animals ask, “What will a high, low, or normal test result specifi- are likely to have “normal” results in all tests of a 20-test cally mean in terms of making a correct diagnosis, pro- profile. The clinician should not over interpret small changes viding accurate prognostic information, or choosing an from reference intervals. appropriate therapeutic plan?” If the answer is meaningful (i.e., it will change some action taken by the clinician), the Abnormal results in normal animals are often only test is worth the cost. Normal laboratory results may elimi- slightly above or below the reference interval. The mag- nate certain diseases (i.e., have high negative predictive nitude of a change helps determine one’s confidence value [NPV]) and can be as valuable as abnormal results. that a disease is present. Large alterations usually allow greater confidence that the animal is abnormal, because NOTE: To choose the appropriate test that will provide they are less likely the result of statistical chance. With a specific diagnostic answer, a very specific question must many tests, increasing magnitude of deviation from be asked. normal also reflects a more severe disease and worsening prognosis. Laboratory methods vary in their ability to provide SIMPLE STATISTICS AND PRACTICAL the same result when a sample is repeatedly analyzed (i.e., INTERPRETATIONS analytical precision). The coefficient of variation (CV) is often used to indicate the precision of an assay. Assays A reasonable level of skepticism about laboratory results with a low CV have a high degree of precision; small should be maintained. Clinicians should not believe all changes in results can be attributed to changes in the numbers. All laboratory data should be interpreted in the patient and not random variation in the assay itself. 1