Effects of carprofen, meloxicam and deracoxib on platelet function in dogs

Background: Cyclosporine has been shown to alter platelet plasma membranes and have a hypercoagulable effect in humans, leading to thromboembolic complications.Hypothesis/Objectives: Our hypothesis was that by modulating platelet reactivity, cyclosporine increases the risk of thromboembolic complications. The objective was to determine the effects of cyclosporine on primary hemostasis in normal dogs.Animals: Eight healthy, intact female dogs. Methods: A repeated-measures design utilized flow cytometry to evaluate platelet expression of platelet reactivity markers (P-selectin and phosphatidylserine) and COX-1 and COX-2 during the administration of 2 cyclosporine dosages (19 mg/kg q12h [immunosuppressive dosage] and 5 mg/kg q24h [atopy dosage]). Urine 11-dehydro-thromboxane-B 2 (11-dTXB 2 ) concentration was normalized to urine creatinine concentration, and platelet function was analyzed by PFA-100.Results: After a week of the immunosuppressive dosage, all platelet reactivity markers showed a significant decrease in mean fluorescent intensity (MFI). After the atopy dosage, only P-selectin and COX-2 MFI demonstrated a change from baseline, decreasing by 29% (P = .013) and 31% (P = .003), respectively. Urinary 11-dTXB 2 -to-creatinine ratio significantly increased at all time points during the immunosuppressive dosage, but no significant change occurred during administration of the atopy dosage. PFA-100 closure times using collagen/ADP cartridges increased by 62% (P = .008) with the immunosuppressive dosage and decreased by 45% with the atopy dosage (P = .035). No significant changes in closure times occurred with collagen/epinephrine cartridges.Conclusions and Clinical Importance: Our study suggests that, similar to what is observed in humans, cyclosporine alters the platelet plasma membrane and increases thromboxane production in dogs, especially at immunosuppressive dosages.

Section: Discussionmentioning

confidence: 90%

The Effects of Cyclosporine on Platelet Function and Cyclooxygenase Expression in Normal Dogs

Thomason

Lunsford

Pinchuk

et al. 2012

“…However, a possible confounding factor in our study was that 3 dogs were receiving concurrent nonsteroidal anti‐inflammatory drugs (NSAIDs—meloxicam or aspirin). Nonsteroidal anti‐inflammatory drugs affect platelet function and are associated with gastrointestinal bleeding in dogs . Therefore, it is suspected that concurrent NSAID use could have contributed to the observed melena and overall decreased survival to discharge and underlines the importance of thorough history taking upon initial evaluation.…”

Section: Discussionmentioning

confidence: 99%

Detection and dynamics of anti‐platelet antibodies in thrombocytopenic dogs with and without idiopathic immune thrombocytopenia

Shropshire

Dow

Lappin

2020

Background Antiplatelet antibodies are detected in multiple diseases including primary immune thrombocytopenia (ITP). Dynamics of how these antibodies change over time in ITP is unknown in dogs. Hypothesis/Objectives Antiplatelet antibodies (APA) will be detected in thrombocytopenic dogs with multiple etiologies and dynamics of APA in dogs with ITP can be used to evaluate response to treatment and relapse. Determine APA at the time of diagnosis in thrombocytopenic dogs and serially in primary ITP dogs. Animals Seventy‐nine thrombocytopenic dogs and 28 primary ITP dogs. Methods Direct flow cytometry was performed in thrombocytopenic dogs at initial evaluation and serially in suspected primary ITP dogs. In primary ITP dogs, a 2‐tailed Fisher's exact test was performed comparing survival to discharge between dogs with and without melena and to relate response to treatment and relapse to changes in APA and platelet count (repeated measures analysis, Spearman correlation). Results Twenty percent (16/79) of thrombocytopenic non‐ITP dogs with infectious, neoplastic, or other diseases and all primary ITP dogs were positive for APA. Melena at initial evaluation was associated with decreased survival to discharge (odds ratio 0.06; P = .01). Persistence of APA was not associated with response to treatment, but recurrence of antibodies was associated with relapse (odds ratio 205.0; P < .01). There was no difference in percentage of APA or platelet count at initial diagnosis between dogs that did or did not respond to treatment. Conclusions and Clinical Importance Serial monitoring of APA in dogs with primary ITP appeared beneficial for determining relapse of disease.

“…Unfortunately, we then experienced an instrument malfunction, and, because most dogs had already received their 1st dose of aspirin, we could not repeat the testing. Instead, we elected to repeat “baseline” samples 4 weeks after completion of aspirin treatment, which is supported by a 14‐day washout period being adequate for closure times to return to normal in dogs after administration of various nonsteroidal anti‐inflammatory drugs . Similarly, after administration of an anti‐inflammatory dose of aspirin (10 mg/kg BID for 10 days) to normal dogs, collagen/epinephrine cartridge closure times returned to normal in all dogs within 14 days of discontinuing the medication (unpublished data) .…”

Section: Discussionmentioning

confidence: 99%

“…A power analysis was performed before study initiation, based on results from a previous study evaluating the effects of nonsteroidal anti‐inflammatory drugs on platelet function . The results of this analysis indicated that a sample size of 27 dogs would be needed to achieve a power value of 0.80 for detection of aspirin‐induced changes in platelet function.…”

Section: Methodsmentioning

confidence: 99%

Cyclooxygenase Expression and Platelet Function in Healthy Dogs Receiving Low‐Dose Aspirin

Dudley

Thomason

Fritz

et al. 2012

Background Low dose aspirin is used to prevent thromboembolic complications in dogs, but some animals are non-responsive to the anti-platelet effects of aspirin (‘aspirin resistance’). Hypothesis/Objectives That low dose aspirin would inhibit platelet function, decrease thromboxane synthesis, and alter platelet cyclooxygenase (COX) expression. Animals Twenty-four healthy dogs Methods A repeated measures study. Platelet function (PFA-100® closure time, collagen/epinephrine), platelet COX-1 and COX-2 expression, and urine 11-dehydro-thromboxane B2 (11-dTXB2) was evaluated prior to and during aspirin administration (1 mg/kg Q24 hours PO, 10 days). Based on prolongation of closure times after aspirin administration, dogs were divided into categories according to aspirin responsiveness: responders, non-responders, and inconsistent responders. Results Low dose aspirin increased closure times significantly (62% by Day 10, P<0.001), with an equal distribution among aspirin responsiveness categories, 8 dogs per group. Platelet COX-1 mean fluorescent intensity (MFI) increased significantly during treatment, 13% on Day 3 (range, −29.7%–136.1%) (P=0.047) and 72% on Day 10 (range, −0.37–210.36%) (P<0.001). Platelet COX-2 MFI increased significantly by 34% (range, −29.2–270.4%) on Day 3 (P = 0.003) and 74% (range, −19.7–226.2%) on Day 10 (P<0.001). Urinary 11-dTXB2 concentrations significantly (P=0.005, P<0.001) decreased at both time points. There was no difference between aspirin responsiveness and either platelet COX expression or thromboxane production. Conclusions and Clinical Importance Low dose aspirin consistently inhibits platelet function in approximately one third of healthy dogs, despite decreased thromboxane synthesis and increased platelet COX expression in most dogs. Pre-treatment COX isoform expression did not predict aspirin resistance.