A prospective evaluation of rivaroxaban on haemostatic parameters in apparently healthy dogs.

The purpose of this study was to determine the effect of rivaroxaban (RIV) on haemostatic parameters assessed by prothrombin time (PT), activated partial thromboplastin time (aPTT) and kaolin-activated thromboelastography (TEG) in apparently healthy dogs administered 1 mg kg-1 orally once daily for 1 week. Eleven dogs had a baseline complete blood count (CBC), fibrinogen, platelet count, serum chemistry profile, PT, aPTT, and TEG performed. Each dog was then administered approximately 1.0 mg kg-1 of RIV orally once daily for 1 week and the CBC, fibrinogen, platelet count, serum chemistry profile, PT, aPTT, and TEG was re-evaluated. Any side effects attributed to RIV were noted at this time. One dog was excluded due to identification of a macrocytic thrombocytopenia on pre-treatment blood work. The remaining 10 enrolled dogs completed the study. Dogs received a median dose of 1.02 mg kg-1 (range 0.94-1.17 mg kg-1 ) of RIV once daily and was associated with a significant increase in pulse, packed cell volume, total solids, platelet count, fibrinogen and a significant decrease in mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration. There was no significant change in PT, aPTT or any TEG parameters. The RIV appeared well tolerated with one dog having one episode of vomiting on day 4 but otherwise no other side effects were identified clinically or on recheck blood work. The results of this study suggests that RIV at a dose of 1 mg kg-1 orally once daily is safe and well tolerated but does not cause a significant prolongation of PT, aPTT or TEG parameters.

In vitro effects of doxorubicin and tetrathiomolybdate on canine hemangiosarcoma cells.

OBJECTIVE To assess the in vitro effects of doxorubicin and tetrathiomolybdate (TM) on cells from a canine hemangiosarcoma cell line. SAMPLE Cultured cells from the canine hemangiosarcoma-derived cell line DEN-HSA. PROCEDURES Cells were treated with TM (0 to 1.5µM), doxorubicin (0 to 5µM), or both with or without 24 hours of pretreatment with ascorbic acid (750µM). Degree of cellular cytotoxicity was measured with a colorimetric assay. Long-term growth inhibition was assessed with a 10-day colony-formation assay. Induction of apoptosis was quantitated by fluorometric assessment of caspase-3 and -7 activation. Formation of reactive oxygen species (ROS) was also detected fluorometrically. RESULTS Exposure of cells to the combination of TM and doxorubicin resulted in a greater decrease in proliferation and clonogenic survival rates than exposure to each drug alone. This treatment combination increased ROS formation and apoptosis to a greater extent than did doxorubicin or TM alone. Ascorbic acid inhibited both TM-induced ROS formation and apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the enhancement in cytotoxic effects observed with DEN-HSA cell exposure to the combination of doxorubicin and TM was achieved through an increase in ROS production. These findings provide a rationale for a clinical trial of this treatment combination in dogs with hemangiosarcoma.