Assessing Methods to Monitor Rivaroxaban Therapy and the Viability of the Calibrated Automated Thrombogram (CAT) using Low Plasma Volumes in Dogs

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University of Guelph

Hypercoagulability, thrombosis, and the use of anti-thrombotic drugs in companion animals are important areas of research in veterinary medicine. There is a paucity of information regarding dosing, effect, and monitoring of anti-thrombotic drugs, such as rivaroxaban, in clinically ill animals.

In the first study, 12 client-owned dogs diagnosed with hypercoagulability and/or thromboembolic disease and prescribed rivaroxaban, were recruited. Blood samples were collected prior to treatment, then 1-week and 1 to 3-months after initiation of therapy. The hemostatic tests prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, rivaroxaban specific anti-Xa assay (raXa), thromboelastography (TEG) with strong activators, and thrombin generation (TG) were performed at each visit (3 hours after rivaroxaban dosing). There was a strong correlation between raXa and PT (p<0.001). The raXa was strongly positively correlated with TG variables- time to peak (ttpeak, p<0.001) and lag time (lag time, p<0.001), and negatively correlated with TG variables- endogenous thrombin potential (ETP, p<0.001) and peak (peak, p<0.001). There was poor correlation between raXa and aPTT, fibrinogen, and all TEG variables.

In the second study, archived plasma samples from dogs previously determined to have low (hypocoagulable, n=10), normal (n=10), and high (hypercoagulable, n=10) thrombin generation potential were used. Method comparison was performed for the calibrated automated thrombogram (CAT) using standard (80 μL plasma, 20 μL reagent- method 1) and low volume (40 μL plasma, 10 μL reagent- method 2) plasma and reagent, respectively. Four parameters of the TG curve were assessed: lag time; ETP; peak; and ttpeak. There was excellent agreement between methods 1 and 2 for all parameters.

In conclusion, PT and TG were found to strongly correlate with raXa and may be a convenient method to monitor hypercoagulable dogs receiving rivaroxaban therapy. Additionally, low volume CAT appears to be a valid alternative to the standard testing method in dogs with a range of thrombin generation potentials.

rivaroxaban, dog, thrombin generation, prothrombin time