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Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs

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  • 1 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens GA 30602
  • | 2 Department of Clinical Studies, Matthew J Ryan Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
  • | 3 Department of Clinical Studies, Matthew J Ryan Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104
  • | 4 Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens GA 30602
  • | 5 Department of Clinical Studies, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104
  • | 6 Section of Critical Care and Anesthesia, Widener Large Animal Hospital, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19382
  • | 7 Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095
  • | 8 Department of Clinical Studies, Matthew J Ryan Hospital, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104

Abstract

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.

Abstract

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.

Contributor Notes

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.

Address correspondence to Dr. Brainard.