Reference Intervals from Hospital-Based Data for Hematologic and Serum Chemistry Values in Dogs

병원자료에 근거한 혈액 및 혈액화학 검사항목의 참고구간 설정

  • Kwon, Young-Wook (Dogvill Animal Hospital) ;
  • Pak, Son-Il (School of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
  • 권영욱 (도그빌 동물병원) ;
  • 박선일 (강원대학교 수의학부대학.동물의학종합연구소)
  • Published : 2010.02.28

Abstract

Reference interval is critical for interpreting laboratory results, monitoring response to therapy and predicting the prognosis of the patients in clinical settings. The aim of the present study was to update established reference intervals for routine hematologic and serum chemistry values for a population of clinically healthy dogs (range, 1-8 years) seen in an animal hospital. Blood was obtained by venipuncture while animals were physically restrained, and samples were analyzed for 9 chemistries on MS9-5H (Melot Schloesing Lab, France) and 6 hematology on Vet Test 8008 (IDEXX, USA). Data from 105 dogs (52 males and 53 females) for hematology and 113 dogs (37 males and 76 females) for chemistry were used to determine reference intervals using the parametric, nonparametric and bootstrap methods. Prior to analysis, all parameters were tested for normal distribution using Anderson-Darling criterion. Of the 9 biochemical analytes, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, total protein, and glucose concentrations did not fit normal distribution for both original and transformed data. All but eosinophil count satisfied normal distribution for either original or transformed data. Parametric method can be used for original cholesterol concentrations, RBC, WBC, and neutrophil counts. This technique can also be used for power-transformed values of blood urea nitrogen concentrations and for logarithm of lymphocyte and monocyte counts. Non-parametric or bootstrap method was the preferred choice for the remaining 7 biochemical parameters and eosinophil count as they did not follow normal distributions. All three statistical techniques performed in similar reference intervals. When establishing reference intervals for clinical laboratory data, it is essential to assess the distribution of the original data to increase the accuracy of the interval, and non-parametric or bootstrap methods are of alternative for the data that do not fit normal distribution.

References

  1. Brun-Hansen HC, Kampen AH, Lund A. Hematologic values in calves during the first 6 months of life. Vet Clin Pathol 2006; 35: 182-187. https://doi.org/10.1111/j.1939-165X.2006.tb00111.x
  2. Ceriotti F, Hinzmann R, Panteghini M. Reference intervals: the way forward. Ann Clin Biochem 2009; 46: 8-17. https://doi.org/10.1258/acb.2008.008170
  3. Chan MK, Seiden-Long I, Aytekin M, Quinn F, Ravalico T, Ambruster D, Adeli K. Canadian Laboratory Initiative on Pediatric Reference Interval Database (CALIPER): pediatric reference intervals for an integrated clinical chemistry and immunoassay analyzer, Abbott ARCHITECT ci8200. Clin Biochem 2009; 42: 885-891. https://doi.org/10.1016/j.clinbiochem.2009.01.014
  4. Concordet D, Geffré A, Braun JP, Trumel C. A new approach for the determination of reference intervals from hospitalbased data. Clin Chim Acta 2009; 405: 43-48. https://doi.org/10.1016/j.cca.2009.03.057
  5. Hansen AM, Garde AH, Eller NH. Estimation of individual reference intervals in small sample sizes. Int J Hyg Environ Health 2007; 210: 471-478. https://doi.org/10.1016/j.ijheh.2007.01.012
  6. Kaneco JJ, Harvey JW, Bruss ML. Clinical biochemistry of domestic animals. 5th ed. New York: Academic press. 1997: 1-20.
  7. Linnet K. Two-stage transformation systems for normalization of reference distributions evaluated. Clin Chem 1987; 33: 381-386.
  8. Linnet K. Testing normality of transformed data. Appl Statist 1988; 37: 180-186. https://doi.org/10.2307/2347337
  9. Linnet K. Estimation of the limit of detection with a bootstrap-derived standard error by a partly non-parametric approach. Application to HPLC drug assays. Clin Chem Lab Med 2005; 43: 394-399. https://doi.org/10.1515/CCLM.2005.071
  10. Lumsden JH. Normal or reference values: questions and comments. Vet Clin Pathol 1998; 27: 102-106. https://doi.org/10.1111/j.1939-165X.1998.tb01027.x
  11. Michael DW, Harold T. Small animal clinical diagnosis by laboratory methods. 4th ed. New York: Saunders. 2004: 96-97.
  12. NCCLS (National Committee for Clinical Laboratory Standards). How to define and determine reference intervals in the clinical laboratory. Approved guidelines NCCLS document C28-A, NCCLS. Villanova. 1995.
  13. Nelson RW, Couto CG. Small animal internal medicine. 2nd ed. New York: Mosby. 2003: 1160-1173.
  14. Petitclerc C, Solberg HE. Approved recommendation (1987) on the theory of reference values. Part 2. Selection of individuals for the production of reference values. J Clin Chem Clin Biochem 1987; 25: 639-644.
  15. Petitclerc C. Normality: the unreachable star? Clin Chem Lab Med 2004; 42: 698-701. https://doi.org/10.1515/CCLM.2004.119
  16. Reed AH, Wu GT. Evaluation of a transformation method for estimation of normal range. Clin Chem 1974; 20: 576-581.
  17. Ruan C, Wu Y, Okada T, Motoi S, Kondo T, Jiang M, Xin X, Peng L, Ichihara K, Ikeda Y. Studies on reference intervals for platelet counts in three cities in China and one in Japan. Thromb Haemost 2002; 88: 111-114.
  18. Solberg HE. Approved recommendations (1987) on the theory of reference values. Part 5. Statistical treatment of collected reference values. Determination of reference limits. J Clin Chem Clin Biochem 1987; 25: 656-656.
  19. Solberg HE, Grasbeck R. Reference values. Adv Clin Chem 1989; 27: 1-79. https://doi.org/10.1016/S0065-2423(08)60181-X
  20. Solberg HE. The IFCC recommendation on estimation of reference intervals. The RefVal program. Clin Chem Lab Med 2004; 42: 710-714. https://doi.org/10.1515/CCLM.2004.121
  21. Thienpont LM, Van Uytfanghe K, De Leenheer AP. Reference measurement systems in clinical chemistry. Clin Chim Acta 2002; 323: 73-87. https://doi.org/10.1016/S0009-8981(02)00188-2
  22. Trowbridge EA, Reardon DM, Bradey L, Hutchinson D, Warren CW. Automated haematology: construction of univariate reference ranges for blood cell count and size. Med Lab Sci 1989; 46: 23-32.