Effects of acepromazine maleate on platelet function assessed by use of adenosine diphosphate activated– and arachidonic acid– activated modified thromboelastography in healthy dogs

Bobbi J. Conner Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Rita M. Hanel Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Bernard D. Hansen Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Alison A. Motsinger-Reif Bioinformatics Research Center, Department of Statistics, College of Agriculture and Life Sciences

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Makoto Asakawa Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Clifford R. Swanson Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Abstract

Objective—To evaluate the effect of acepromazine maleate administered IV on platelet function assessed in healthy dogs by use of a modified thromboelastography assay.

Animals—6 healthy adult mixed-breed dogs.

Procedures—Dogs received each of 3 treatments (saline [0.9% NaCl] solution [1 to 2 mL, IV] and acepromazine maleate [0.05 and 0.1 mg/kg, IV]) in a randomized crossover study with a minimum 3-day washout period between treatments. From each dog, blood samples were collected via jugular venipuncture immediately before and 30 and 240 minutes after administration of each treatment. A modified thromboelastography assay, consisting of citrated kaolin–activated (baseline assessment), reptilase-ADP–activated (ADP-activated), and reptilase-arachidonic acid (AA)–activated (AA-activated) thromboelastography, was performed for each sample. Platelet inhibition was evaluated by assessing the percentage change in maximum amplitude for ADP-activated or AA-activated samples, compared with baseline values. Percentage change in maximum amplitude was analyzed by use of Skillings-Mack tests with significance accepted at a family-wise error rate of P < 0.05 by use of Bonferroni corrections for multiple comparisons.

Results—No significant differences were found in the percentage change of maximum amplitude from baseline for ADP-activated or AA-activated samples among treatments at any time.

Conclusions and Clinical Relevance—Platelet function in dogs, as assessed by use of a modified thromboelastography assay, was not inhibited by acepromazine at doses of 0.05 or 0.1 mg/kg, IV. This was in contrast to previous reports in which it was suggested that acepromazine may alter platelet function via inhibition of ADP and AA.

Abstract

Objective—To evaluate the effect of acepromazine maleate administered IV on platelet function assessed in healthy dogs by use of a modified thromboelastography assay.

Animals—6 healthy adult mixed-breed dogs.

Procedures—Dogs received each of 3 treatments (saline [0.9% NaCl] solution [1 to 2 mL, IV] and acepromazine maleate [0.05 and 0.1 mg/kg, IV]) in a randomized crossover study with a minimum 3-day washout period between treatments. From each dog, blood samples were collected via jugular venipuncture immediately before and 30 and 240 minutes after administration of each treatment. A modified thromboelastography assay, consisting of citrated kaolin–activated (baseline assessment), reptilase-ADP–activated (ADP-activated), and reptilase-arachidonic acid (AA)–activated (AA-activated) thromboelastography, was performed for each sample. Platelet inhibition was evaluated by assessing the percentage change in maximum amplitude for ADP-activated or AA-activated samples, compared with baseline values. Percentage change in maximum amplitude was analyzed by use of Skillings-Mack tests with significance accepted at a family-wise error rate of P < 0.05 by use of Bonferroni corrections for multiple comparisons.

Results—No significant differences were found in the percentage change of maximum amplitude from baseline for ADP-activated or AA-activated samples among treatments at any time.

Conclusions and Clinical Relevance—Platelet function in dogs, as assessed by use of a modified thromboelastography assay, was not inhibited by acepromazine at doses of 0.05 or 0.1 mg/kg, IV. This was in contrast to previous reports in which it was suggested that acepromazine may alter platelet function via inhibition of ADP and AA.

Contributor Notes

Dr. Conner's present address is Department of Companion Animal Clinical Studies, Faculty of Veterinary Medicine, University of Pretoria, Onderstepoort 0110, Republic of South Africa.

Supported by the Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University.

Presented as an oral presentation at the 34th American College of Veterinary Anesthesiologists Annual Meeting, Chicago, September 2009.

Address correspondence to Dr. Hanel (rita_hanel@ncsu.edu).
  • 1.

    Smith SA. The cell-based model of coagulation. J Vet Emerg Crit Care (San Antonio) 2009; 19:310.

  • 2.

    Barr SC, Ludders JW, Looney AL, et al. Platelet aggregation in dogs after sedation with acepromazine and atropine and during subsequent general anesthesia and surgery. Am J Vet Res 1992; 53:20672070.

    • Search Google Scholar
    • Export Citation
  • 3.

    Kanaho Y, Kometani M, Sato T, et al. Mechanism of inhibitory effect of some amphiphilic drugs on platelet aggregation induced by collagen, thrombin or arachidonic acid. Thromb Res 1983; 31:817831.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Jain MK, Eskow K, Kuchibhotla J, et al. Correlation of inhibition of platelet aggregation by phenothiazines and local anesthetics with their effects on a phospholipid bilayer. Thromb Res 1978; 13:10671075.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Buchanan GR, Martin V, Levine PH, et al. The effects of “anti-platelet” drugs on bleeding times and platelet aggregation in normal human subjects. Am J Clin Pathol 1977; 68:355359.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Simeonova G, Dinev DN, Todorova II, et al. Influence of hypothermia and acidosis upon some indices of blood coagulation in three schemes of anaesthesia in dogs. Vet Arhiv 2005; 75:233242.

    • Search Google Scholar
    • Export Citation
  • 7.

    Palsgaard-Van Lue A, Jensen AL, Strøm H, et al. Comparative analysis of haematological, haemostatic, and inflammatory parameters in canine venous and arterial blood samples. Vet J 2007; 173:664668.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Bay JD, Scott MA, Hans JE, et al. Reference values for activated coagulation time in cats. Am J Vet Res 2000; 61:750753.

  • 9.

    Risselada M, Polyak MM, Ellison GW, et al. Postmortem evaluation of surgery site leakage by use of in situ isolated pulsatile perfusion after partial liver lobectomy in dogs. Am J Vet Res 2010; 71:262267.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Graham HA, Leib MS. Effects of prednisone alone or prednisone with ultralow-dose aspirin on the gastroduodenal mucosa of healthy dogs. J Vet Intern Med 2009; 23:482487.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Wiinberg B, Jensen AL, Rojkjaer R, et al. Validation of human recombinant tissue factor-activated thromboelastography on citrated whole blood from clinically healthy dogs. Vet Clin Pathol 2005; 34:389393.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Bauer N, Eralp O, Moritz A. Establishment of reference intervals for kaolin-activated thromboelastography in dogs including an assessment of the effects of sex and anticoagulant use. J Cardiothorac Vasc Anesth 2006; 20:531535.

    • Search Google Scholar
    • Export Citation
  • 13.

    Wiinberg B, Jensen AL, Rozanski E, et al. Tissue factor activated thromboelastography correlates to clinical signs of bleeding in dogs. Vet J 2009; 179:121129.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Sinnott VB, Otto CM. Use of thromboelastography in dogs with immune-mediated hemolytic anemia: 39 cases (2000–2008). J Vet Emerg Crit Care 2009; 19:484488.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Otto CM, Rieser TM, Brooks MB, et al. Evidence of hypercoagulability in dogs with parvoviral enteritis. J Am Vet Med Assoc 2000; 217:15001504.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Kristensen AT, Wiinberg B, Jessen LR, et al. Evaluation of human recombinant tissue factor-activated thromboelastography in 49 dogs with neoplasia. J Vet Intern Med 2008; 22:140147.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Wiinberg B, Jensen AL, Johansson PI, et al. Thromboelastographic evaluation of hemostatic function in dogs with disseminated intravascular coagulation. J Vet Intern Med 2008; 22:357365.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Craft RM, Chavez JJ, Bresee SJ, et al. A novel modification of the thromboelastograph assay, isolating platelet function, correlates with optical platelet aggregation. J Lab Clin Med 2004; 143:301309.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Egberg N, Nordström S. Effects of reptilase-induced intravascular coagulation in dogs. Acta Physiol Scand 1970; 79:493505.

  • 20.

    Brainard BM, Kleine SA, Papich MG, et al. Pharmacodynamic and pharmacokinetic evaluation of clopidogrel and the carboxylic acid metabolite SR 26334 in healthy dogs. Am J Vet Res 2010; 71:822830.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Brainard BM, Meredith CP, Callan MB, et al. Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs. Am J Vet Res 2007; 68:251257.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Bochsen L, Wiinberg B, Kjelgaard-Hansen M, et al. Evaluation of the TEG platelet mapping assays in blood donors. Thromb J 2007; 5:3.

  • 23.

    Skillings JH, Mack GA. On the use of a Friedman-type statistic in balanced and unbalanced block designs. Technometrics 1981; 23:171177.

  • 24.

    Chatfield M, Mander A. The Skillings-Mack test (Friedman test when there are missing data). Stata J 2009; 9:299305.

  • 25.

    Clemmons RM, Meyers KM. Acquisition and aggregation of canine blood platelets: basic mechanisms of function and differences because of breed origin. Am J Vet Res 1984; 45:137144.

    • Search Google Scholar
    • Export Citation
  • 26.

    McMichael M. Primary hemostasis. J Vet Emerg Crit Care 2005; 15:18.

  • 27.

    Feldman BF, Zinkl JG, Jain NC, et al. Platelet biology. In: Feldman BF, Zinkl JG, Jain NC, et al, eds. Schalm's veterinary hematology. 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2000;460.

    • Search Google Scholar
    • Export Citation
  • 28.

    Tantry US, Bliden KP, Gurbel PA. Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J Am Coll Cardiol 2005; 46:17051709.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Hashem A, Kietzmann M, Scherkl R. Pharmacokinetics and bioavailability of acepromazine in plasma of the dog. Dtsch Tierarztl Wochenschr 1992; 99:396398.

    • Search Google Scholar
    • Export Citation
  • 30.

    Mansell PD, Parry BW. Effect of acepromazine, xylazine and thiopentone on factor VIII activity and von Willebrand factor antigen concentration in dogs. Aust Vet J 1992; 69:187190.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Iselin BM, Willimann PFX, Seiffert B, et al. Isolated reduction of hematocrit does not compromise in vitro blood coagulation. Br J Anaesth 2001; 87:246249.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Shibata J, Hasegawa J, Siemens HJ, et al. Hemostasis and coagulation at a hematocrit level of 0.85: functional consequences of erythrocytosis. Blood 2003; 101:44164422.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Larsen OH, Ingerslev J, Sørensen B. Whole blood laboratory model of thrombocytopenia for use in evaluation of hemostatic interventions. Ann Hematol 2007; 86:217221.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34.

    Hughes JE. Troubleshooting tips for coagulation. Adv Med Lab Prof 2002; 14:1925.

  • 35.

    Castellone DD. Specimens for coagulation. Lab Med 1998; 29:467.

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