Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs.
OBJECTIVE
To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs.


METHODS
8 client-owned dogs with clinical signs of osteoarthritis.


METHODS
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 E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha 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 alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib.


CONCLUSIONS
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.
Brainard
Benjamin M
BM
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens GA 30602, USA.
Meredith
Craig P
CP
Callan
Mary Beth
MB
Budsberg
Steven C
SC
Shofer
Francis S
FS
Driessen
Bernd
B
Otto
Cynthia M
CM
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004283:Dog Diseases / Q000188:drug therapy; D004285:Dogs; D005260:Female; D005786:Gene Expression Regulation; D006487:Hemostasis / Q000187:drug effects*; D008297:Male; D000077239:Meloxicam; D010003:Osteoarthritis / Q000188:drug therapy / Q000662:veterinary; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000235:genetics / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D000096926:Benzenesulfonamides
D001241:Aspirin; D002227:Carbazoles; D016861:Cyclooxygenase Inhibitors; D000077239:Meloxicam; D011453:Prostaglandins; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; C007005:carprofen; C471996:deracoxib; D000096926:Benzenesulfonamides