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Comparison of Thromboelastography, Conventional Coagulation Tests and Clotting Time in Preclinical Investigations of Anticoagulant Drugs in Rodents
  • Xinrong Yang,   
  • Boning Huang,   
  • Ping Tang,   
  • Liuqing Lin,   
  • Baoqin Lin *

Received: 11 Sep 2024 | Revised: 24 Oct 2024 | Accepted: 28 Oct 2024 | Published: 22 Apr 2025

Abstract

Background: This aimed to compare thromboelastography (TEG), conventional coagulation tests (CCTs) and clotting time (CT) during the detection of coagulation in rodents. Methods: The TEG, CCTs and CT were detected in blood samples from the abdominal aorta to assess the coagulation system in rodents administered with anticoagulants. Similarly, the CT test was performed on blood samples from the retro-orbital venous plexus of mice. Subsequently, the sensitivity of CT to detect coagulation changes in mice administered with different anticoagulants was assessed. Finally, factors influencing the clotting time were investigated, including the sources of blood samples, laparotomy, fasting, irrigation, gender, and different technicians. Results: TEG failed to detect rivaroxaban-induced changes in the coagulation system of rats. In contrast, APTT, PT, and CT were significantly prolonged following rivaroxaban administration in rats. APTT and PT exhibited higher sensitivity compared to the clotting time. Furthermore, the clotting time of mice was more sensitive relative to that of rats. Moreover, laparotomy, fasting, irrigation, and gender did not influence the clotting time, however, different technicians did. Conclusion: In summary, TEG may not be an appropriate method for assessing the impact of drug-induced prolongation of clotting time in rodents. CCTs and CT are effective screening methods for anticoagulant agents. Besides, the CT appears to be ideal for application in the primary screening of anticoagulant drugs in mice, while CCTs are suitable for rats.

References 

  • 1.
    Khan, F.; Tritschler, T.; Kahn, S.R.; et al. Venous thromboembolism. Lancet 2021, 398, 64–77. https://doi.org/10.1016/S0140-6736(20)32658-1.
  • 2.
    Lutsey, P.L.; Zakai, N.A. Epidemiology and prevention of venous thromboembolism. Nat. Rev. Cardiol. 2023, 20, 248–262. https://doi.org/10.1038/s41569-022-00787-6.
  • 3.
    Fredenburgh, J.C.; Weitz, J.I. New anticoagulants: Moving beyond the direct oral anticoagulants. J. Thromb. Haemost. 2021, 19, 20–29. https://doi.org/10.1111/jth.15126.
  • 4.
    Kruger, P.C.; Eikelboom, J.W.; Douketis, J.D.; et al. Deep vein thrombosis: Update on diagnosis and management. Med. J. Aust. 2019, 210, 516–524. https://doi.org/10.5694/mja2.50201.
  • 5.
    Tritschler, T.; Kraaijpoel, N.; Le Gal, G.; et al. Venous Thromboembolism: Advances in Diagnosis and Treatment. JAMA 2018, 320, 1583–1594. https://doi.org/10.1001/jama.2018.14346.
  • 6.
    Di Nisio, M.; Van Es, N.; Büller, H.R. Deep vein thrombosis and pulmonary embolism. Lancet 2016, 388, 3060–3073. https://doi.org/10.1016/S0140-6736(16)30514-1.
  • 7.
    Cohen, T.; Haas, T.; Cushing, M.M. The strengths and weaknesses of viscoelastic testing compared to traditional coagulation testing. Transfusion 2020, 60, S6. https://doi.org/10.1111/trf.16073.
  • 8.
    Mao, C.; Xiong, Y.; Fan, C. Comparison between thromboelastography and conventional coagulation assays in patients with deep vein thrombosis. Clin. Chim. Acta 2021, 520, 208–213. https://doi.org/10.1016/j.cca.2021.06.019.
  • 9.
    Holcomb, J.B.; Minei, K.M.; Scerbo, M.L.; et al. Admission Rapid Thrombelastography Can Replace Conventional Coagulation Tests in the Emergency Department: Experience With 1974 Consecutive Trauma Patients. Ann. Surg. 2012, 256, 476–486. https://doi.org/10.1097/SLA.0b013e3182658180.
  • 10.
    Hartert, H. Blutgerinnungsstudien mit der Thrombelastographie, einem neuen Untersuchungsverfahren. Klin. Wochenschr. 1948, 26, 577–583. https://doi.org/10.1007/BF01697545.
  • 11.
    Redfern, R.E.; Fleming, K.; March, R.L.; et al. Thromboelastography-Directed Transfusion in Cardiac Surgery: Impact on Postoperative Outcomes. Ann. Thorac. Surg. 2019, 107, 1313–1318. https://doi.org/10.1016/j.athoracsur.2019.01.018.
  • 12.
    Pietri, L.D.; Montalti, R.; Bolondi, G.; et al. Intraoperative thromboelastography as a tool to predict postoperative thrombosis during liver transplantation. World J. Transplant. 2020, 10, 345–355. https://doi.org/10.5500/wjt.v10.i11.345.
  • 13.
    Subramanian, M.; Kaplan, L.J.; Cannon, J.W. Thromboelastography-Guided Resuscitation of the Trauma Patient. JAMA Surg. 2019, 154, 1152. https://doi.org/10.1001/jamasurg.2019.3136.
  • 14.
    Muzaffar, S.N.; Azim, A.; Siddiqui, S.S. Thromboelastography for Predicting Disseminated Intravascular Coagulation (DIC) in Sepsis. Shock 2022, 57, 759. https://doi.org/10.1097/SHK.0000000000001929.
  • 15.
    Ramiz, S.; Hartmann, J.; Young, G.; et al. Clinical utility of viscoelastic testing (TEG and ROTEM analyzers) in the management of old and new therapies for hemophilia. Am. J. Hematol. 2019, 94, 249–256. https://doi.org/10.1002/ajh.25319.
  • 16.
    Karon, B.S. Why is everyone so excited about thromboelastrography (TEG)? Clin. Chim. Acta 2014, 436, 143–148. https://doi.org/10.1016/j.cca.2014.05.013.
  • 17.
    Carroll, R.C.; Craft, R.M.; Langdon, R.J.; et al. Early evaluation of acute traumatic coagulopathy by thrombelastography. Transl. Res. 2009, 154, 34–39. https://doi.org/10.1016/j.trsl.2009.04.001.
  • 18.
    Voleisis, A.; Kazys, R.; Voleisiene, B.; et al. Ultrasonic method for monitoring the clotting process during whole blood coagulation. Ultrasonics 2017, 78, 146–151. https://doi.org/10.1016/j.ultras.2017.02.017.
  • 19.
    Biggs, R.; Macmillan, R.L. The Errors of Some Haematological Methods as They Are Used in a Routine Laboratory. J. Clin. Pathol. 1948, 1, 269–287. https://doi.org/10.1136/jcp.1.5.269.
  • 20.
    Heran, C.; Morgan, S.; Kasiewski, C.; et al. Antithrombotic efficacy of RPR208566, a novel factor Xa inhibitor, in a rat model of carotid artery thrombosis. Eur. J. Pharmacol. 2000, 389, 201–207. https://doi.org/10.1016/S0014-2999(99)00902-4.
  • 21.
    Perzborn, E.; Strassburger, J.; Wilmen, A.; et al. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939—An oral, direct Factor Xa inhibitor. J. Thromb. Haemost. 2005, 3, 514–521. https://doi.org/10.1111/j.1538-7836.2005.01166.x.
  • 22.
    Brill, J.B.; Badiee, J.; Zander, A.L.; et al. The rate of deep vein thrombosis doubles in trauma patients with hypercoagulable thromboelastography. J. Trauma. Acute Care Surg. 2017, 83, 413–419. https://doi.org/10.1097/TA.0000000000001618.
  • 23.
    Conversy, B.; Blais, M.C.; Dunn, M.; et al. Anticoagulant activity of oral rivaroxaban in healthy dogs. Vet. J. 2017, 223, 5–11. https://doi.org/10.1016/j.tvjl.2017.03.006.
  • 24.
    Evans, L.A.; Tansey, C.; Wiebe, M.; et al. A prospective evaluation of rivaroxaban on haemostatic parameters in apparently healthy dogs. Vet. Med. Sci. 2019, 5, 317–324. https://doi.org/10.1002/vms3.161.
  • 25.
    Gentry, P.A. Comparative aspects of blood coagulation. Vet. J. Lond. Engl. 1997. 2004, 168, 238–251. https://doi.org/10.1016/j.tvjl.2003.09.013.
  • 26.
    Lechner, R.; Helm, M.; Müller, M.; et al. In-vitro study of species-specific coagulation differences in animals and humans using rotational thromboelastometry (ROTEM). BMJ Mil. Health 2019, 165, 356–359. https://doi.org/10.1136/jramc-2018-001092.
  • 27.
    Stettler, G.R.; Moore, E.E.; Moore, H.B.; et al. Thrombelastography indicates limitations of animal models of trauma-induced coagulopathy. J. Surg. Res. 2017, 217, 207–212. https://doi.org/10.1016/j.jss.2017.05.027.
  • 28.
    Wohlauer, M.V.; Moore, E.E.; Harr, J.; et al. A Standardized technique for performing thromboelastography in rodents. Shock 2011, 36, 524–526. https://doi.org/10.1097/SHK.0b013e31822dc518.
  • 29.
    Herrmann, R.; Thom, J.; Wood, A.; et al. Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban. Thromb. Haemost. 2014, 112, 989–995. https://doi.org/10.1160/TH13-07-0607.
  • 30.
    Dias, J.D.; Norem, K.; Doorneweerd, D.D.; et al. Use of Thromboelastography (TEG) for detection of new oral anticoagulants. Arch. Pathol. Lab. Med. 2015, 139, 665–673. https://doi.org/10.5858/arpa.2014-0170-OA.
  • 31.
    Giani, M.; Russotto, V.; Pozzi, M.; et al. Thromboelastometry, thromboelastography, and conventional tests to assess anticoagulation during extracorporeal support: A Prospective Observational Study. ASAIO J. 2021, 67, 196–200. https://doi.org/10.1097/MAT.0000000000001196.
  • 32.
    Kakkos, S.K.; Gohel, M.; Baekgaard, N.; et al. Editor’s Choice–European Society for Vascular Surgery (ESVS) 2021 Clinical practice guidelines on the management of venous thrombosis. Eur. J. Vasc. Endovasc. Surg. 2021, 61, 9–82. https://doi.org/10.1016/j.ejvs.2020.09.023.
  • 33.
    Hull, R.D.; Raskob, G.E.; Hirsh, J.; et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis. N. Engl. J. Med. 1986, 315, 1109–1114. https://doi.org/10.1056/NEJM198610303151801.
  • 34.
    Wannamethee, S.G.; Papacosta, O.; Lennon, L.; et al. Haematological variables and risk of future venous thromboembolism in the British Regional Heart Study on men. Combined D-dimer and APTT as a predictive test for thromboembolism? Br. J. Haematol. 2022, 198, 587–594. https://doi.org/10.1111/bjh.18288.
  • 35.
    Lippi, G.; Favaloro, E.J. Laboratory monitoring of warfarin in the era of direct oral anticoagulants. Lancet Haematol. 2015, 2, e223–e224. https://doi.org/10.1016/S2352-3026(15)00075-7.
  • 36.
    Chan, N.; Sobieraj-Teague, M.; Eikelboom, J.W. Direct oral anticoagulants: Evidence and unresolved issues. Lancet Lond. Engl. 2020, 396, 1767–1776. https://doi.org/10.1016/S0140-6736(20)32439-9.
  • 37.
    Perzborn, E.; Roehrig, S.; Straub, A.; et al. Rivaroxaban: A new oral factor Xa inhibitor. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 376–381. https://doi.org/10.1161/ATVBAHA.110.202978.
  • 38.
    Zhou, W.; Abdurahman, A.; Umar, A.; et al. Effects of cydonia oblonga miller extracts on blood hemostasis, coagulation and fibrinolysis in mice, and experimental thrombosis in rats. J. Ethnopharmacol. 2014, 154, 163–169. https://doi.org/10.1016/j.jep.2014.03.056.
  • 39.
    Doering, C.J.; Wagg, C.R.; Caulkett, N.A.; et al. Comparison of arterial and venous whole blood clot initiation, formation, and strength by thromboelastography in anesthetized swine. Blood Coagul. Fibrinolysis. 2014, 25, 20–24. https://doi.org/10.1097/MBC.0b013e328364672a.
  • 40.
    Groves, D.S.; Winegar, D.A.; Fernandez, L.G.; et al. Comparison of coagulation parameters in arterial and venous blood in cardiac surgery measured using the quantra system. J. Cardiothorac. Vasc. Anesth. 2019, 33, 976–984. https://doi.org/10.1053/j.jvca.2018.08.201.
  • 41.
    Schuurman, P.R.; Albrecht, K.W. Intraoperative changes of transcranial Doppler velocity: Relation to arterial oxygen content and whole-blood viscosity. Ultrasound Med. Biol. 1999, 25, 151–154. https://doi.org/10.1016/S0301-5629(98)00135-5.
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DOI
10.53941/ijddp.2025.100008
Issue
Volume 4, Issue 2
How to Cite
Yang, X.; Huang, B.; Tang, P.; Lin, L.; Lin, B. Comparison of Thromboelastography, Conventional Coagulation Tests and Clotting Time in Preclinical Investigations of Anticoagulant Drugs in Rodents. International Journal of Drug Discovery and Pharmacology 2025, 4 (2), 100008. https://doi.org/10.53941/ijddp.2025.100008.
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