Study of Blood Coagulation Parameters in Mlac:WR Rat Produced by the National Laboratory Animal Center
Keywords:
Mlac:WR rat, Blood coagulation, Prothrombin time (PT), Activated partial thromboplastin time (APTT), Coagulation factorsAbstract
Wistar rats have been used as animal models for testing the toxicity of pharmacological products. Blood coagulation tests are used to detect abnormalities in the blood clotting mechanism. Currently, the Wistar rats produced by the National Laboratory Animal Center have not been studied for their blood coagulation values. Therefore, this study measured the blood coagulation parameters, prothrombin time (PT) and activated partial thromboplastin time (APTT), in Mlac:WR rats using a SYSMEX CA-660 automated coagulation analyzer. The results showed that both sex and age significantly affected the mean PT and APTT values at the 95% confidence level (p < 0.05). In terms of stability, plasma samples stored at -20°C for 2 weeks prior to analysis tended to have shorter PT values but significantly prolonged APTT values (p < 0.001). Furthermore, Mlac:WR rats that received sterile water via oral gavage for 90 consecutive days showed no significant differences in coagulation values compared to the non-oral gavage group, except for the male APTT value, which significantly decreased in the oral gavage group (p < 0.001). This study demonstrates that sex, age, and variations in the daily routines of experimental animals, as well as pre-analytical sample storage conditions, can influence blood coagulation parameters in Wistar rats.
References
Gale AJ. Continuing education course #2: current understanding of hemostasis. Toxicol Pathol 2011; 39(1): 273-80.
Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth 2014; 58(5): 515-23.
Winter WE, Flax SD, Harris NS. Coagulation testing in the core laboratory. Lab Med 2017; 48(4): 295-313.
Kurata M, Horii I. Blood coagulation tests intoxicological studies--review of methods and their significance for drug safety assessment. J Toxicol Sci 2004; 29(1): 13-32.
Tomlinson L, Boone LI, Ramaiah L, Penraat KA, von Beust BR, Ameri M, et al. Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries. Vet Clin Pathol 2013; 42(3): 252-69.
Zaidi SRH, Rout P. Interpretation of blood clotting studies and values (PT, PTT, aPTT, INR, anti-factor Xa, D-dimer) [updated 2025 Oct 8]. In: StatPearls. [online]. Treasure Island, FL: StatPearls Publishing; 2026. [cited 2026 May 10]. Available from: URL: https://www.ncbi.nlm.nih.gov/books/NBK604215.
Levi M, Seligsohn U, Kaushansky K. Classification, clinical manifestations, and evaluation of disorders of hemostasis. In: Kaushansky K, Lichtman MA, Prchal JT, Levi MM, Press OW, Burns LJ, Caligiuri M, editors. Williams hematology. 9th ed. New York: McGraw-Hill Education; 2016. p. 1985-1992.
Organisation for Economic Co-operation and Development (OECD). Test Guideline No. 408: Repeated dose 90-day oral toxicity study in rodents. [online]. 2025; [cited 2026 May 10]; [17 screens]. Available from: URL: https://www.oecd.org/content/dam/oecd/en/publications/reports/2018/06/test-no-408-repeated-dose-90-day-oral-toxicity-study-in-rodents_g1gh2931/9789264070707-en.pdf.
Bonnichsen M, Dragsted N, Hansen AK. The welfare impact of gavaging laboratory rats. Anim Welf 2005; 14(3): 223-7.
Brown AP, Dinger N, Levine BS. Stress produced by gavage administration in the rat. Contemp Top Lab Anim Sci 2000; 39(1): 17-21.
Clements PJM, Bolon B, McInnes E, Mukaratirwa S, Scudamore C. Chapter 17, Animal models in toxicologic research: rodents. In: Haschek and Rousseaux's handbook of toxicologic pathology Vol. 1. 4th ed. London: Academic Press; 2022. p. 653-694.
Clinical and Laboratory Standards Institute (CLSI). Collection, transport, and processing of blood specimens for testing plasma-based coagulation assays and molecular hemostasis assays; approved guideline. 5th ed. [online]. 2008; [cited 2026 May 10]; [11 screens]. Available from: URL: https://webstore.ansi.org/preview-pages/clsi/preview_h21-a5.pdf.
Lemini C, Jaimez R, Franco Y. Gender and inter-species influence on coagulation tests of rats and mice. Thromb Res 2007; 120(3): 415-9.
Goyal VK, Kakade S, Pandey SK, Gothi AK, Nirogi R. Determining the effect of storage conditions on prothrombin time, activated partial thromboplastin time and fibrinogen concentration in rat plasma samples. Lab Anim 2015; 49(4): 311-8.
Ingram GI, Hills M. The prothrombin time test: effect of varying citrate concentration. Thromb Haemost 1976; 36(1): 230-6.
Adcock DM, Kressin DC, Marlar RA. Effect of 3.2% vs 3.8% sodium citrate concentration on routine coagulation testing. Am J Clin athol 1997; 107(1): 105-10.
O'Brien SR, Sellers TS, Meyer DJ. Artifactual prolongation of the activated partial thromboplastin time associated with emoconcentration in dogs. J Vet Intern Med 1995; 9(3): 169-70.
Kurata M, Noguchi N, Kasuga Y, Sugimoto T, Tanaka K, Hasegawa T. Prolongation of PT and APTT under excessive anticoagulant in plasma from rats and dogs. J Toxicol Sci 1998; 23(2): 149-53.
Quick AJ, Stanley-Brown M, Bancroft FW. A study of the coagulation defect in hemophilia and in jaundice. Am J Med Sci 1935; 190(4): 501-11.
Jolly DW, Kadis BM, Nelson TE Jr. Estrogen and prothrombin synthesis. The prothrombinogenic action of estrogen. Biochem Biophys Res Commun 1977; 74(1): 41-9.
Kaplan AP, Silverberg M. The coagulation-kinin pathway of human plasma. Blood 1987; 70(1): 1-15.
Cushman M. Effects of hormone replacement therapy and estrogen receptor modulators on markers of inflammation and coagulation. Am J Cardiol 2002; 90(1 Suppl 1): F7-F10.
Tabata H, Nakamura S, Matszawa T. Some species differences in the false prolongation of prothrombin times and activated partial thromboblastin times in toxicology. Comp Haematol Int 1995; 5: 140-4.
Boehm O, Zur B, Koch A, Tran N, Freyenhagen R, Hartmann M, et al. Clinical chemistry reference database for Wistar rats and C57/BL6 mice. Biol Chem 2007; 388(5): 547-54.
Patel S, Patel S, Kotadiya A, Patel S, Shrimali B, Joshi N, et al. Age-related changes in hematological and biochemical profiles of Wistar rats. Lab Anim Res 2024; 40(1): 7. (12 pages).
Casella S, Giannetto C, Fazio F, Giudice E, Piccione G. Assessment of prothrombin time, activated partial thromboplastin time, and fibrinogen concentration on equine plasma samples following different storage conditions. J Vet Diagn Invest 2009; 21(5): 674-8.
Favaloro EJ, Funk DM, Lippi G. Pre-analytical variables in coagulation testing associated with diagnostic errors in hemostasis. Lab Med 2012; 43(2): 1-10.
Woodhams B, Girardot O, Blanco MJ, Colesse G, Gourmelin Y. Stability of coagulation proteins in frozen plasma. Blood Coagul Fibrinolysis 2001; 12(4): 229-36.
Zürcher M, Sulzer I, Barizzi G, Lämmle B, Alberio L. Stability of coagulation assays performed in plasma from citrated whole blood transported at ambient temperature. Thromb Haemost 2008; 99(2): 416-26.
Seligsohn U, Zivelin A, Bar-Shani S. Cold-promoted activation of factor VII: is it a problem under blood bank conditions? Haemostasis 1983; 13(3): 186-91.
Saito H, Ratnoff OD. Alteration of factor VII activity by activated Fletcher factor (a plasma kallikrein): a potential link between the intrinsic and extrinsic blood-clotting systems. J Lab Clin Med 1975; 85(3): 405-15.
Obeagu EI. Stress-induced hemostasis: mechanisms and implications for health. Ann Med Surg (Lond) 2025; 87(6): 3300-9.
von Känel R, Mills PJ, Fainman C, Dimsdale JE. Effects of psychological stress and psychiatric disorders on blood coagulation and fibrinolysis: a biobehavioral pathway to coronary artery disease?. Psychosom Med 2001; 63(4): 531-44.
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