Effect of dalteparin administration on thrombin generation kinetics in healthy dogs.

Abstract

BACKGROUND Dalteparin is used to prevent thrombotic complications in dogs. Measurement of anti-factor Xa (anti-FXa) activity is currently used for monitoring therapy, but remains a nonfunctional test. The calibrated automated thrombogram (CAT) could be a suitable approach for functional monitoring. OBJECTIVES We hypothesized that the CAT will detect decreased endogenous thrombin potential (ETP) in healthy dogs receiving dalteparin. METHODS Twenty-four healthy adult Beagles were randomly allocated to 4 equal groups. A single subcutaneous (SC) dose of 50 U/kg, 100 U/kg, or 150 U/kg of dalteparin was given. Platelet-poor plasma (PPP) was collected over a 24-hour period and evaluated by thrombin generation (TG) via CAT, anti-FXa activity, and APTT. Analysis was performed with a repeated-measures general linear mixed model, and the treated groups were compared to a placebo group. RESULTS Time, dose, and time-dose interaction significantly affected ETP (P < .0001 for all effects), peak (P < .0001 for all effects), rate index (P < .0006 for all effects), and anti-FXa activity (P < .0001 for all effects). No significant time trend was detected in the control group. Dogs receiving the 100 U/kg dalteparin SC injection showed the most homogeneous response of ETP inhibition among treated groups. The % inhibition of ETP from baseline increased nonlinearly as a function of anti-FXa activity (r2 = .8186). CONCLUSIONS The CAT assay can be employed to measure the effects of dalteparin at different doses in healthy dogs, showing sensitivity to time- and dose-dependent changes in ETP and other TG variables. Further investigation of the CAT as a tool for monitoring low molecular weight heparin therapy in dogs is warranted.

DOI: 10.1111/vcp.12489

Cite this paper

@article{GaraBoivin2017EffectOD, title={Effect of dalteparin administration on thrombin generation kinetics in healthy dogs.}, author={Carolyn Gara-Boivin and J{\'e}r{\^o}me R E de Castillo and Marilyn E Dunn and Christian B{\'e}dard}, journal={Veterinary clinical pathology}, year={2017}, volume={46 2}, pages={269-277} }