Utility and safety of nafamostat mesilate for anticoagulation in dogs

Vet Med Sci. 2023 Jan;9(1):68-75. doi: 10.1002/vms3.1002. Epub 2022 Nov 21.

Abstract

Background: Surgical interventions are recommended for cases of advanced mitral regurgitation, however, limited facilities are available. The most prominent complication in such procedures is heparin-derived bleeding. An alternative anticoagulant to heparin, nafamostat mesilate (NM), can reduce the occurrence of complications associated with heparin such as bleeding or shock.

Objectives: This study aimed to evaluate the utility and safety of using NM during anaesthesia in canines.

Methods: Six healthy adult Beagle dogs were anaesthetised, and NM was administered intravenously as a 10 mg/kg bolus dose over 5 min, followed by a continuous infusion of 10 mg/kg/h over 20 min. Blood tests and blood pressure measurements were performed at 0, 5, 25 and 55 min after NM administration.

Results: Activated thromboplastin times at 0, 25 and 55 min were 13.0 ± 0.7 s, 106.7 ± 13.3 s and 28.2 ± 2.9 s, respectively, with a significant difference between 0 and 25 min (p < 0.01) only. No significant differences were observed in prothrombin time, antithrombin, fibrinogen and fibrin degradation product concentrations between timepoints. Activated clotting times (ACTs) at 0, 5, 25 and 55 min were 119.5 ± 9.6 s, 826.7 ± 78.6 s, 924.8 ± 42.4 s and 165.2 ± 13.5 s, respectively. Significant differences were observed between 0 and 5 min (p < 0.05) and between 0 and 25 min (p < 0.05). Blood pressure changes occurred in four dogs (66.7%). No other serious adverse effects were observed.

Conclusions: ACT results indicated that NM use in anaesthetised healthy dogs was sufficient to obtain procedural anticoagulation with minimal adverse effects. However, these preliminary data require validation in further studies on cardiopulmonary bypass surgery.

Keywords: anticoagulants; cardiac surgery; cardiopulmonary bypass; mitral valve insufficiency.

MeSH terms

  • Animals
  • Anticoagulants* / adverse effects
  • Benzamidines
  • Dogs
  • Guanidines / adverse effects
  • Heparin*

Substances

  • nafamostat
  • Anticoagulants
  • Heparin
  • Guanidines
  • Benzamidines