Objective—To determine effects of therapeutic dosages of aspirin, carprofen, deracoxib, and meloxicam on platelet function and systemic prostaglandin concentrations in healthy dogs.
Animals—10 hound-crossbred dogs.
Procedures—Aspirin (10 mg/kg, PO, q 12 h), carprofen (4.4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), meloxicam (0.1 mg/kg, PO, q 24 h), and a placebo were administered for 7 days in a random order to each of 10 healthy dogs; there was a 21-day washout period between subsequent treatments. One-stage prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and plasma concentrations of thromboxane (TX)B2 and 6-keto prostaglandin (PG)F1α were measured before and after treatment administration. Platelet function was assessed by use of a platelet-function analyzer and aggregation.
Results—Aspirin, carprofen, and meloxicam did not significantly affect platelet function. Deracoxib caused a mild decrease in platelet aggregation induced by 50μM ADP. Platelet number, Hct, PT, aPTT, and plasma TXB2 and 6-keto PGF1α concentrations were unchanged after NSAID administration. Meloxicam administration resulted in a significant decrease in fibrinogen concentration, but results remained within the laboratory reference interval.
Conclusions and Clinical Relevance—Oral administration of commonly used NSAIDs at therapeutic dosages in healthy dogs did not alter plasma TXB2 and 6-keto PGF1α concentrations. Deracoxib administration resulted in a minor abnormality in platelet aggregation. Anti-inflammatory doses of aspirin did not affect platelet function as measured by use of optical aggregometry and a platelet-function analyzer. Further evaluation of the effects of aspirin and cyclooxygenase-2–selective inhibitors on hemostasis should be performed.
Objective—To describe the effects of prednisone and acetylsalicylic acid (ASA) on results of thromboelastography in healthy dogs.
Animals—16 male mixed-breed dogs.
Procedures—Dogs were randomly assigned to 3 treatment groups (4 dogs/group) that received prednisone (median dose, 2.07 mg/kg), ASA (median dose, 0.51 mg/kg), or both drugs, PO, every 24 hours from days 0 through 6. Another group received no treatment (control dogs; n = 4). Thromboelastography variables (reaction time, clotting time, α-angle, maximum amplitude [MA], global clot strength, coagulation index, and percentage of clot lysis at 60 minutes [CL60]) were evaluated in blood samples collected (prior to drug administration in treated dogs) on days 0 (baseline), 2, 4, and 6.
Results—Administration of ASA alone did not alter TEG variables. For treatment effect, mean global clot strength was increased in the prednisone and drug combination groups, compared with values for control dogs; MA was also increased in the prednisone and drug combination groups, compared with that of controls. For treatment-by-time effect, median CL60 was increased in the prednisone group on day 6, compared with baseline value in the same dogs and with median CL60 of the control group on day 6. Median CL60 was also increased in the drug combination group on day 6, compared with the baseline value and with that of the control group on day 6.
Conclusions and Clinical Relevance—Prednisone administered at approximately 2 mg/kg/d, PO, for 7 days with or without concurrently administered ASA increased clot strength and decreased clot lysis in healthy dogs.
To describe daily changes in serum concentrations of hyaluronic acid (HA), a biomarker of endothelial glycocalyx degradation, in dogs with septic peritonitis and to determine whether relationships exist among serum concentrations of HA and biomarkers of inflammation and patient fluid status.
8 client-owned dogs.
Serum samples that had been collected for a previous study and stored at −80°C were used. Blood samples were collected at admission and daily thereafter during hospitalization and were analyzed for concentrations of HA and interleukins 6, 8, and 10. Patient data including acute patient physiologic and laboratory evaluation score, type and amount of fluids administered daily, and daily CBC and lactate concentration results were recorded. To determine the significant predictors of HA concentration, a general linear mixed model for repeated measures was developed.
All dogs survived to discharge. Concentrations of HA ranged from 18 to 1,050 ng/mL (interquartile [25th to 75th percentile] range, 49 to 119 ng/mL) throughout hospitalization. Interleukin-6 concentration was a significant predictor of HA concentration as was total administered daily fluid volume when accounting for interleukin-6 concentration. When fluid volume was analyzed independent of inflammatory status, fluid volume was not a significant predictor. Concentrations of HA did not significantly change over time but tended to increase on day 2 or 3 of hospitalization.
CONCLUSIONS AND CLINICAL RELEVANCE
Results supported the theory that inflammation is associated with endothelial glycocalyx degradation. Dogs recovering from septic peritonitis may become more susceptible to further endothelial glycocalyx damage as increasing fluid volumes are administered.
OBJECTIVE To determine whether canine protein C (CnPC) had antichemotactic effects on canine neutrophils, whether endothelial protein C receptor (EPCR) was expressed on canine neutrophils, and the role of EPCR in neutrophil chemotaxis.
SAMPLE Neutrophils isolated from blood samples from healthy dogs (n = 6) and sick dogs with (2) or without (3) an inflammatory leukogram.
PROCEDURES Neutrophils were analyzed by reverse transcriptase PCR assay and flow cytometry for detection of EPCR mRNA and protein expression, respectively. Neutrophils were incubated with CnPC zymogen or canine activated protein C (CnAPC), with or without RCR-379 (an anti–human EPCR antibody). Neutrophils were then allowed to migrate through a filter membrane toward a chemokine. Untreated neutrophils served as positive control samples. Migration was quantified by fluorescence measurement, and chemotaxis index (Chx) values (fluorescence of test sample/fluorescence of positive control sample) were computed.
RESULTS The cDNA for EPCR was amplified, and EPCR expression was detected on neutrophil surfaces. Obtained Chx values were significantly higher in cells treated with RCR-379 than in cells treated with CnPC or CnAPC alone. The Chx values for neutrophils treated with RCR-379 were not significantly different from 1, whereas those for neutrophils treated without RCR-379 were significantly less than 1. The effects of RCR-379 on neutrophil migration were independent of concentration or activation status of protein C.
CONCLUSIONS AND CLINICAL RELEVANCE Canine neutrophils expressed EPCR, and inhibition of neutrophil chemotaxis by CnPC and CnAPC depended on EPCR. Interventions with EPCR signaling may have therapeutic application in dogs.