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  • Title: Thrombolysis with rt-PA under Rivaroxaban Anticoagulation in a Hypertensive Rat Model of Intraluminal Middle Cerebral Artery Occlusion.
    Author: Izuma H, Oka F, Ishihara H, Inoue T, Suehiro E, Nomura S, Suzuki M.
    Journal: J Stroke Cerebrovasc Dis; 2018 Oct; 27(10):2761-2767. PubMed ID: 30056000.
    Abstract:
    BACKGROUND: The aim of this study was to assess the risk and the threshold of hemorrhagic transformation (HT) after treatment with recombinant tissue plasminogen activator (rtPA) under the novel oral anticoagulant, rivaroxaban. METHODS: Fifty-three spontaneous hypertensive rats were used in this study. We performed transient middle cerebral artery occlusion for 270 minutes. Placebo, 10 mg/kg or 20 mg/kg rivaroxaban were administered via a stomach tube 180 minutes after induction of ischemia, and rtPA (10 mg/kg) was administered just before reperfusion. Ninety minutes after rivaroxaban administration we measured the rivaroxaban plasma concentration and prothrombin time (PT). HT volume was assessed by hemoglobin spectrophotometry. Additionally, infarct volume, IgG leakage volume, and neurological outcome were assessed. RESULTS: Rivaroxaban plasma concentration and PT increased in a dose dependent manner but were lower than human peak levels after a once-daily dose of 20 mg rivaroxaban. HT volume increased after treatment with 20 mg/kg rivaroxaban compared with placebo treated controls or those treated with 10 mg/kg rivaroxaban (26.5 ± 5.4, 26.8 ± 8.7, and 41.4 ± 12.6 μL in placebo, 10 mg/kg, and 20 mg/kg treated groups, respectively; P < .05). CONCLUSIONS: Our results suggest that even at therapeutic plasma concentrations, rivaroxaban may increase the risk of HT after thrombolysis in some conditions, such as hypertension and/or a prolonged ischemic period.
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