Therapeutic monitoring of rivaroxaban in dogs using thromboelastography and prothrombin time

J Vet Intern Med. 2019 May;33(3):1322-1330. doi: 10.1111/jvim.15478. Epub 2019 Mar 11.

Abstract

Background: The chromogenic anti-Xa assay, the gold standard for monitoring the anti-Xa effect of rivaroxaban, is not available as a cage-side diagnostic test for use in a clinical setting.

Hypothesis/objectives: To evaluate clinical modalities for measuring the anticoagulant effects of rivaroxaban using a point-of-care prothrombin time (PT) and thromboelastography (TEG).

Animals: Six healthy Beagle dogs.

Methods: Prospective, experimental study. Four different doses of rivaroxaban (0.5, 1, 2, and 4 mg/kg) were administered PO to dogs. Single PO and 3 consecutive dosing regimens also were assessed. Plasma rivaroxaban concentration was determined using a chromogenic anti-Xa assay, point-of-care PT, and TEG analysis with 4 activators (RapidTEG, 1 : 100 tissue factor [TF100], 1 : 3700 tissue factor [TF3700], and kaolin), and results were compared. Spearman correlation coefficients were calculated between ratios (peak to baseline PT; peak reaction time [R] of TEG to baseline [R] of TEG) and anti-Xa concentration.

Results: Anti-Xa concentration had a significant correlation with point-of-care PT (R = 0.82, P < .001) and RapidTEG-TEG, TF100-TEG, and TF3700-TEG (R = 0.76, P < .001; R = 0.82, P < .001; and R = 0.83, P < .001, respectively).

Conclusions and clinical importance: Overall, a 1.5-1.9 × delay in PT and R values of TEG 3 hours after rivaroxaban administration is required to achieve therapeutic anti-Xa concentrations of rivaroxaban in canine plasma. The R values of TEG, specifically using tissue factors (RapidTEG, TF100, TF3700) and point-of-care PT for rivaroxaban can be used practically for therapeutic monitoring of rivaroxaban in dogs.

Keywords: TEG; anti-Xa; oral anticoagulant; point-of-care PT test.

MeSH terms

  • Animals
  • Dogs / blood
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / pharmacokinetics
  • Factor Xa Inhibitors / pharmacology*
  • Male
  • Prospective Studies
  • Prothrombin Time / veterinary*
  • Rivaroxaban / administration & dosage
  • Rivaroxaban / pharmacokinetics
  • Rivaroxaban / pharmacology*
  • Thrombelastography / veterinary*

Substances

  • Factor Xa Inhibitors
  • Rivaroxaban