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  • Author or Editor: Daniel J. Fletcher x
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Abstract

Objective—To determine minimum plasma concentrations of the antifibrinolytic agents tranexamic acid (TEA) and ϵ-aminocaproic acid (EACA) needed to completely inhibit fibrinolysis in canine and human plasma after induction of hyperfibrinolysis.

Samples—Pooled citrated plasma from 7 dogs and commercial pooled citrated human plasma.

Procedures—Concentrations of EACA from 0 μg/mL to 500 μg/mL and of TEA from 0 μg/mL to 160 μg/mL were added to pooled citrated canine and human plasma. Hyperfibrinolysis was induced with 1,000 units of tissue plasminogen activator/mL, and kaolin-activated thromboelastography was performed in duplicate. The minimum concentrations required to completely inhibit fibrinolysis 30 minutes after maximum amplitude of the thromboelastography tracing occurred were determined.

Results—Minimum plasma concentrations necessary for complete inhibition of fibrinolysis by EACA and TEA in pooled canine plasma were estimated as 511.7 μg/mL (95% confidence interval [CI], 433.2 to 590.3 μg/mL) and 144.7 μg/mL (95% CI, 125.2 to 164.2 μg/mL), respectively. Concentrations of EACA and TEA necessary for complete inhibition of fibrinolysis in pooled human plasma were estimated as 122.0 μg/mL (95% CI, 106.2 to 137.8 μg/mL) and 14.7 μg/mL (95% CI, 13.7 to 15.6 μg/mL), respectively.

Conclusions and Clinical Relevance—Results supported the concept that dogs are hyperfibrinolytic, compared with humans. Higher doses of EACA and TEA may be required to fully inhibit fibrinolysis in dogs.

Full access
in American Journal of Veterinary Research

Abstract

Case Description—A 4-year-old sexually intact female French Bulldog was evaluated because of lethargy, anorexia, and chronic rhinitis-sinusitis. The dog had nasal discharge of 18 months' duration; dorsal rhinotomies were performed 3 months and 2 weeks prior to referral.

Clinical Findings—On initial evaluation, intraventricular pneumocephalus and sinusitis were diagnosed; CSF analysis revealed high total protein concentration and mononuclear pleocytosis. The dog's condition improved with treatment. Two weeks after discharge, it was treated by a local veterinarian because of upper airway obstruction; 3 days later, the dog was referred because of seizures. Computed tomography revealed a large fluid-filled, left lateral ventricle and a soft tissue mass protruding through a cribriform plate defect. The mass was histologically consistent with brain tissue. Findings of clinicopathologic analyses were unremarkable. Results of cytologic examination of a CSF sample were indicative of septic, suppurative inflammation, and bacteriologic culture of CSF yielded Escherichia coli.

Treatment and Outcome—Amputation of the herniated olfactory bulb and antimicrobial treatment resolved the septic meningoencephalitis, but neurologic deficits recurred 6 weeks later. Definitive correction of the cribriform plate defect with bone and fascial grafts was attempted. Postoperative rotation of the bone graft resulted in cerebral laceration and hemorrhage, and the dog was euthanized.

Clinical Relevance—Findings suggest that following dorsal rhinotomy and nasal polypectomy surgery, the dog developed herniation of the left olfactory bulb, intra-ventricular pneumocephalus, and septic meningo-encephalitis because of a cribriform plate defect. Care must be taken to prevent rotation of bone grafts used in cribriform defect repair.

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in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE To determine pharmacodynamic and pharmacokinetic profiles of aminocaproic acid (ACA) by use of a thromboelastography (TEG)-based in vitro model of hyperfibrinolysis and high-performance liquid chromatography–mass spectrometry.

ANIMALS 5 healthy adult dogs.

PROCEDURES A single dose of injectable ACA (20, 50, or 100 mg/kg) or an ACA tablet (approximately 100 mg/kg) was administered orally. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, and 240 minutes after ACA administration for pharmacokinetic analysis. Samples were obtained at 0, 60, and 240 minutes for pharmacodynamic analysis by use of a TEG model of hyperfibrinolysis.

RESULTS No adverse effects were detected. In the hyperfibrinolysis model, after all doses, a significantly higher TEG maximum amplitude (clot strength), compared with baseline, was detected at 60 and 240 minutes. Additionally, the percentage of fibrinolysis was reduced from the baseline value at 60 and 240 minutes, with the greatest reduction at 60 minutes. At 240 minutes, there was significantly less fibrinolysis for the 100 mg/kg dose than the 20 mg/kg dose. Maximum plasma ACA concentration was dose dependent. There was no significant difference in pharmacokinetic parameters between 100 mg/kg formulations.

CONCLUSIONS AND CLINICAL RELEVANCE In an in vitro model of hyperfibrinolysis, ACA inhibited fibrinolysis at all doses tested. At 240 minutes after administration, the 100 mg/kg dose inhibited fibrinolysis more effectively than did the 20 mg/kg dose. Thus, ACA may be useful for in vivo prevention of fibrinolysis in dogs.

IMPACT FOR HUMAN MEDICINE These data may improve research models of hyperfibrinolytic diseases.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate pituitary-adrenal function in critically ill dogs with sepsis, severe trauma, and gastric dilatation-volvulus (GDV).

Design—Cohort study.

Animals—31 ill dogs admitted to an intensive care unit (ICU) at Washington State University or the University of Pennsylvania; all dogs had acute critical illness for < 48 hours prior to admission.

Procedures—Baseline and ACTH-stimulated serum cortisol concentrations and baseline plasma ACTH concentrations were assayed for each dog within 24 hours after admission to the ICU. The change in cortisol concentrations (Δ-cortisol) was calculated for each dog. Morbidity and mortality data were recorded for each patient.

Results—Overall, 17 of 31 (55%) acutely critically ill dogs had at least 1 biochemical abnormality suggestive of adrenal gland or pituitary gland insufficiency. Only 1 (3%) dog had an exaggerated response to ACTH stimulation. Dogs with Δ-cortisol ≤ 83 nmol/L were 5.7 times as likely to be receiving vasopressors as were dogs with Δ-cortisol > 83 nmol/L. No differences were detected among dogs with sepsis, severe trauma, or GDV with respect to mean baseline and ACTH-stimulated serum cortisol concentrations, Δ-cortisol, and baseline plasma ACTH concentrations.

Conclusions and Clinical Relevance—Biochemical abnormalities of the hypothalamic-pituitary-adrenal axis indicative of adrenal gland or pituitary gland insufficiency were common in critically ill dogs, whereas exaggerated responses to ACTH administration were uncommon. Acutely ill dogs with Δ-cortisol ≤ 83 nmol/L may be more likely to require vasopressors as part of the treatment plan.

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in Journal of the American Veterinary Medical Association

Abstract

Objective—To compare clinical outcome in dogs with serologically diagnosed acquired myasthenia gravis (MG) treated with pyridostigmine bromide (PYR) with that of dogs treated with mycophenolate mofetil (MMF) and PYR (MMF + PYR).

Design—Retrospective case series.

Animals—27 dogs.

Procedures—Medical records from August 1999 through February 2008 were reviewed to identify dogs with serologically diagnosed acquired MG treated with PYR or MMF + PYR. Data collected for each dog included signalment, whether the dog had megaesophagus or pneumonia (or both), thyroid hormone concentration, remission, time to remission, and survival time. Rates for detection of clinical signs and survival time were compared. Survival time was estimated via the Kaplan-Meier method. Influence of drug treatment protocol on likelihood of remission, time to remission, and survival time was examined. Effects of MMF treatment, megaesophagus, pneumonia, and low serum thyroid hormone concentration on time to remission and survival time were also analyzed.

Results—12 dogs were treated with PYR, and 15 were treated with MMF + PYR. Mortality rates were 33% (PYR) and 40% (MMF + PYR). There was pharmacological remission in 5 and 6 dogs in the PYR and MMF + PYR groups, respectively. No significant differences were detected between treatment groups for remission rate, time to remission, or survival time. Megaesophagus, pneumonia, and low serum thyroid hormone concentration had no significant effect on time to remission or survival time for either treatment group.

Conclusions and Clinical Relevance—The results did not support routine use of MMF for the treatment of dogs with acquired MG.

Restricted access
in Journal of the American Veterinary Medical Association