Gierse JK, Staten NR, Casperson GF, et al. Cloning, expression, and selective inhibition of canine cyclooxygenase-1 and cyclooxygenase-2. Vet Ther 2002;3:270–280.
Jones CJ, Budsberg SC. Physiologic characteristics and clinical importance of the cyclooxygenase isoforms in dogs and cats. J Am Vet Med Assoc 2000;217:721–729.
Gambaro G, Perazella MA. Adverse renal effects of anti-inflammatory agents: evaluation of selective and non-selective cyclooxygenase inhibitors. J Intern Med 2003;253:643–652.
Schafer AI. Effects of nonsteroidal anti-inflammatory therapy on platelets. Am J Med 1999;106:25S–36S.
Streppa HK, Jones CJ, Budsberg SC. Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs in canine blood. Am J Vet Res 2002;63:91–94.
Kawai S, Nishida S, Kato M, et al. Comparison of cyclooxygenase-1 and -2 inhibitory activities of various nonsteroidal anti-inflammatory drugs using human platelets and synovial cells. Eur J Pharmacol 1998;347:87–94.
Fitzgerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. New Engl J Med 2001;345:433–442.
Patrignani P, Sciulli MG, Manarini S, et al. COX-2 is not involved in thromboxane biosynthesis by activated human platelets. J Physiol Pharmacol 1999;50:661–667.
Johnson GJ, Leis LA, Dunlop PC. Thromboxane-insensitive dog platelets have impaired activation of phospholipase C due to receptor-linked G-protein dysfunction. J Clin Invest 1993;92:2469–2479.
Catella-Lawson F, Crofford LJ. Cyclooxygenase inhibition and thrombogenicity. Am J Med 2001;110:28S–32S.
Cohen RA, Shepard JT, Vanhoutte PM. Inhibitory role of the endothelium in the response of isolated coronary arteries to platelets. Science 1983;221:273–274.
Cheng Y, Austin SC, Rocca B, et al. Role of prostacyclin in the cardiovascular response to thromboxane A2. Science 2002;296:539–541.
Catalfamo JL, Dodds WJ. Isolation of platelets from laboratory animals. In:Hawiger J, ed.Methods in enzymology. Vol 169. San Diego Academic Press Inc, 1989;27–34.
Donahue SM, Otto CM. Thromboelastography: a tool for measuring hypercoagulability, hypocoagulability and fibrinolysis. J Vet Emerg Crit Care 2005;15:9–16.
Gurbel PA, Murugesan SR, Lowry DR, et al. Plasma thromboxane and prostacyclin are linearly related and increased in patients presenting with acute myocardial infarction. Prostaglandins Leukot Essent Fatty Acids 1999;61:7–11.
Hickford FH, Barr SC, Erb HN. Effect of carprofen on hemostatic variables in dogs. Am J Vet Res 2001;62:1642–1646.
McAdam BF, Catella-Lawson F, Mardini IA, et al. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A 1999;96:272–277.
Hwang DH. Species variation in platelet aggregation. In:Longnecker GL, ed.The platelets, physiology and pharmacology. New York: Academic Press Inc, 1985;289–305.
Freeman MB, Sicard GA, Valentin LI, et al. The association of in vitro arachidonic acid responsiveness and plasma thromboxane levels with early platelet deposition on the luminal surface of small-diameter grafts. J Vasc Surg 1988;7:554–561.
Boudreaux MK, Dillon AR, Ravis WR, et al. Effects of treatment with aspirin or aspirin/dipyridamole combination in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs. Am J Vet Res 1991;52:1992–1999.
Jackson ML, Searcy GP, Olexson DW. Effect of oral phenylbutazone on whole blood platelet aggregation in the dog. Can J Comp Med 1985;49:271–277.
McCrath DJ, Cerboni E, Frumento RJ, et al. Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction. Anesth Analg 2005;100:1576–1583.
Kazakos GM, Papazoglou LG, Rallis T, et al. Effects of meloxicam on the haemostatic profile of dogs undergoing orthopaedic surgery. Vet Rec 2005;157:444–446.
Catella F, Nowak J, Fitzgerald GA. Measurement of renal and non-renal eicosanoid synthesis. Am J Med 1986;81:23–29.
Todd MK, Goldfarb AH, Kauffman RD, et al. Combined effects of age and exercise on thromboxane B2 and platelet activation. J Appl Phys 1994;76:1548–1552.
Shimada Y, Kutsumi Y, Nishio H, et al. Role of platelets in myocardial ischemia-reperfusion injury in dogs. Jpn Circ J 1997;61:241–248.
Oei HH, Zoganas HC, Sakane Y, et al. Inhibition of thromboxane biosynthesis in splanchnic ischemia shock. Circ Shock 1986;18:95–106.
Edstrom LE, Balkovich M, Slotman GJ. Effect of ischemic skin flap elevation on tissue and plasma thromboxane A2 and prostacyclin production: modification by thromboxane synthetase inhibition. Ann Plast Surg 1988;20:106–111.
Durante W, Sunahara FA. Cardiovascular effects of high frequency ventilation—the possible involvement of thromboxane. Prostaglandins Leukot Med 1987;28:127–139.
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Objective—To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs.
Animals—8 client-owned dogs with clinical signs of osteoarthritis.
Procedures—Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E2, platelet thromboxane B2 (TXB2), and free serum TXB2 and 6-keto-prostaglandin F (PGF)-1α concentrations.
Results—Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and α-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E2 decreased after treatment with carprofen or deracoxib, and platelet TXB2 production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1α did not change significantly after treatment with any of the drugs, although the ratio of free TXB2 to 6-keto-PGF-1α decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib.
Conclusions and Clinical Relevance—At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.
Supported by an interdepartmental grant from the Section of Clinical Studies, Philadelphia, Veterinary Hospital of the University of Pennsylvania and Dr. B. Driessen. Mr. Meredith was supported by Merck & Company Incorporated and the National Institutes of Health.
Presented in part as an abstract at the International Veterinary Emergency and Critical Care Symposium, Atlanta, September 2005, and at the Association of Veterinary Anesthesiologists annual meeting, Atlanta, October, 2005.
The authors thank Dr. Sandra Z. Perkowski and Lisa Reynolds for assistance with prostanoid evaluation.