Comparative Clinical Pathology

, Volume 28, Issue 1, pp 11–20 | Cite as

Toxicologic veterinary clinical pathology—how is it different from diagnostic clinical pathology?

  • Barbara Beust
  • Elizabeth Fiona McInnesEmail author
Review Article


Veterinary clinical pathology is a board examination specialized discipline in veterinary medicine focused on the study and understanding of animal disease based on measured variables and analytes, predominantly in peripheral blood, but also other body fluids, and their diagnostic significance. In clinical veterinary medicine, clinical pathology has been established as a standard component of the diagnostic process for decades, similar to human clinical medicine. Likewise, the collection of clinical pathology data in laboratory animals is an established standard practice in preclinical studies in drug development. However, non-pathologists such as toxicologists and study directors in the pharmaceutical and agrochemical industries can find it difficult to understand the relevance of the clinical pathology data. This review will outline and discuss certain important differences between diagnostic and toxicologic clinical pathology (TCP) and list some typical examples mainly in hematology and clinical chemistry including some important contextual considerations in addition to treatment-related changes in peripheral blood, such as urine; in-life observations; and histopathology. Most importantly, while in clinical diagnostics, the main question is whether an animal or patient is sick or healthy, and in case of obvious disease, what exactly the animal is suffering from, the question in toxicologic clinical pathology is whether there are treatment-related effects that can be determined based on dose-dependent differences in laboratory data between treated groups and the control group with or without statistical significance and of adverse relevance. As in clinical diagnostics, some very specific preanalytic but also analytic considerations are required for scientifically and toxicologically sound final data analysis, interpretation, and reporting.


Clinical pathology Toxicology Hematology Biochemistry Urinalysis 


  1. Abbas AK, Lichtman AHH (2014) Cellular and molecular immunology, 8th edn. Elsevier, AmsterdamGoogle Scholar
  2. Aulbach AD, Schultze E, Tripathi NK, Hall RL, Logan MR, Meyer DJ (2015) Factors affecting urine reagent strip blood results in dogs and nonhuman primates and interpretation of urinalysis in preclinical toxicology studies: a multi-institution contract research organization and biopharmaceutical company perspective. Vet Clin Pathol 44:229–233CrossRefGoogle Scholar
  3. Bennett JS, Gossett KA, McCarthy MP et al (2009) Effects of ketamine hydrochloride on serum biochemical and hematologic variables in rhesus monkeys (Macaca mulatta). Vet Clin Pathol 21:15–18Google Scholar
  4. Blank M, De Feice A, Goodsaid F, Harlow P, Hausner E, Jacobson-Kram D, Taylor W, Thompson A, Throckmorton D, Xiao S (2009) Review of Qualification Data for Biomarkers of Nephrotoxicity Submitted by the Predictive Safety Testing Consortium Biomarker Qualification Review Team Center for Drug Evaluation and Research. U.S. Food and Drug Administration.
  5. Burkhardt JE, Pandher K, Solter PF, Troth SP, Boyce RW, Zabka TS, Ennulat D (2011) Recommendations for the evaluation of pathology data in nonclinical safety biomarker qualification studies. Toxicologic Pathol 39:1129–1137CrossRefGoogle Scholar
  6. Camus MS, Flatland B, Freeman KP, Janice A, Cruz Cardona JA (2015) ASVCP quality assurance guidelines: external quality assessment and comparative testing for reference and in-clinic laboratories. Vet Clin Pathol 44:477–492CrossRefGoogle Scholar
  7. Christensen MB, Langhorn R, Goddard A, Andreasen EB, Moldal E, Tvarijonaviciute A, Kirpensteijn J, Jakobsen S, Persson F, Kjelgaard-Hansen M (2014) Comparison of serum amyloid A and C-reactive protein as diagnostic markers of systemic inflammation in dogs. Can Vet J 55:161–168Google Scholar
  8. Cray C, Zaias J, Altman NH (2009) Acute phase response in animals: a review. Comp Med 59:517–526Google Scholar
  9. Diehl K-H, Hull R, Morton D, Pfister R, Rabemampianina Y, Smith D, Vidal JM, van de Vorstenbosch C, European Federation of Pharmaceutical Industries Association and European Centre for the Validation of Alternative Methods (2001) A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol 21:15–23CrossRefGoogle Scholar
  10. Ennulat D, Walker D, Clemo F, Magid-Slav M, Ledieu D, Graham M, Botts S, Boone L (2010) Effects of hepatic drug- metabolizing enzyme induction on clinical pathology parameters in animals and man. Toxicol Pathol 38:810–828CrossRefGoogle Scholar
  11. Everds NE, Snyder PW, Bailey KL, Bolon B, Creasy DM, Foley GL, Rosol TJ, Sellers T (2013) Interpreting stress responses during routine toxicity studies: a review of the biology, impact, and assessment. Toxicol Pathol 41:560–614CrossRefGoogle Scholar
  12. FDA (2015) Code of federal regulations (CFR) Title 21, part 58, Good Laboratory Practice for nonclinical laboratory studies.
  13. Flatland B, Friedrichs KR, Klenner S (2014) Differentiating between analytical and diagnostic performance evaluation with a focus on the method comparison study and identification of bias. Vet Clin Pathol 43:475–486CrossRefGoogle Scholar
  14. Friedrichs KR, Harr KE, Freeman KP, Szladovits B, Walton RM, Barnhart KF, Blanco-Chavez J, American Society for Veterinary Clinical Pathology (2012) ASVCP reference interval guidelines: determination of de novo reference intervals in veterinary species and other related topics. Vet Clin Pathol 41:441–453CrossRefGoogle Scholar
  15. Geffre A, Braun JP, Trumel C, Concordet D (2009) Estimation of reference intervals from small samples: an example using canine plasma creatinine. Vet Clin Pathol 38:477–484CrossRefGoogle Scholar
  16. Grimes CN, Fry MM (2015) Nonregenerative anemia: mechanisms of decreased or ineffective erythropoiesis. Vet Pathol 52:298–311CrossRefGoogle Scholar
  17. Gunn-Christie RG, Flatland B, Friedrichs KR, Szladovits B, Harr KE, Ruotsalo K, Knoll JS, Wamsley HL, Freeman KP, American Society for Veterinary Clinical Pathology (ASVCP) (2012) ASVCP quality assurance guidelines: control of preanalytical, analytical, and postanalytical factors for urinalysis, cytology, and clinical chemistry in veterinary laboratories. Vet Clin Pathol 41:18–26CrossRefGoogle Scholar
  18. Hall RL, Everds NE (2003) Factors affecting the interpretation of canine and nonhuman primate clinical pathology. Toxicol Pathol 31:6–10CrossRefGoogle Scholar
  19. Heegaard PMH, Miller I, Sorensen NS, Soerensen KE, Skovgaard K (2013) Pig a1-acid glycoprotein: characterization and first description in any species as a negative acute phase protein. PLoS One 8:e68110CrossRefGoogle Scholar
  20. Honjo T, Kuribayashi T, Matsumoto M, Yamazaki S, Yamamoto S (2010) Kinetics of {alpha}2-macroglobulin and {alpha}1-acid glycoprotein in rats subjected to repeated acute inflammatory stimulation. Lab Anim 44:150–154CrossRefGoogle Scholar
  21. Jensen AL, Kjelgaard-Hansen M (2006) Method comparison in the clinical laboratory. Vet Clin Pathol 35:276–286CrossRefGoogle Scholar
  22. Kaneko J, Harvey J, Bruss M (2008) Clinical biochemistry of domestic animals, 6th edn. John Wiley & Sons, ChichesterGoogle Scholar
  23. Ramaiah L, Tomlinson L, Tripathi NK, Cregar LC, Vitsky A, Beust BV, Barlow VG, Reagan WJ, Ennulat D (2017) Principles for assessing adversity in toxicologic clinical pathology. Toxicol Pathol 45:260–266CrossRefGoogle Scholar
  24. Reagan WJ, Irizarry-Rovira A, Poitout-Belissent F, Bolliger AP, Ramaiah SK, Travlos G, Walker D, Bounous D, Walter G, Bone Marrow Working Group of ASVCP/STP (2011) Best practices for evaluation of bone marrow in nonclinical toxicity studies. Toxicol Pathol 39:435–438CrossRefGoogle Scholar
  25. Rütgen BC, Ramona König R, Sabine E, Hammer SE et al (2015) Composition of lymphocyte subpopulations in normal canine lymph nodes. Vet Clinical Pathol 44:58–69CrossRefGoogle Scholar
  26. Sellers RS, Morton D, Michael B et al (2007) Society of Toxicologic Pathology position Paper: organ weight recommendations for toxicology studies. Toxicol Pathol 35:751–755CrossRefGoogle Scholar
  27. Tomlinson L, Boone LI, Ramaiah L, Penraat KA, von Beust BR, Ameri M, Poitout-Belissent FM, Weingand K, Workman HC, Aulbach AD, Meyer DJ, Brown DE, MacNeill AL, Bolliger AP, Bounous DI (2013) Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries. Vet Clin Pathol 42:252–269CrossRefGoogle Scholar
  28. Vap LM, Harr KE, Arnold JE, Freeman KP, Getzy K, Lester S, Friedrichs KR, American Society for Veterinary Clinical Pathology (ASVCP) (2012) ASVCP quality assurance guidelines: control of preanalytical and analytical factors for hematology for mammalian and nonmammalian species, hemostasis, and crossmatching in veterinary laboratories. Vet Clin Pathol 41:8–17CrossRefGoogle Scholar
  29. Weiss DJ, Wardrop J (2010) Schalm’s veterinary hematology, 6th edn. Wiley-Blackwell, BostonGoogle Scholar
  30. Zamfir M, Prefontaine A, Copeman C, Poitout F, Provencher A (2014) Dilution of blood for hematology and biochemistry analysis in rats. ASVCP Annual Conference, Atlanta GA, Abstract. Vet Clin Pathol. 43:4CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  1. 1.CNE (Clinical and Nonclinical Experts GmbH)WinterthurSwitzerland
  2. 2.Internal Research CentreSyngenta LtdBracknellUK

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