Profibrinolytic effects of rivaroxaban are mediated by thrombin-activatable fibrinolysis inhibitor and are attenuated by a naturally occurring stabilizing mutation in enzyme.

Rivaroxaban is a direct factor Xa inhibitor, recently implemented as a favorable alternative to warfarin in anticoagulation therapy. Rivaroxaban effectively reduces thrombin generation, which plays a major role in the activation of thrombin activatable fibrinolysis inhibitor (TAFI) to TAFIa. Based on the antifibrinolytic role of TAFIa, we hypothesized that rivaroxaban would consequently induce more rapid clot lysis. In vitro clot lysis assays were used to explore this hypothesis and additionally determine the effects of varying TAFI levels and a stabilizing Thr325Ile polymorphism (rs1926447) in the TAFI protein on the effects of rivaroxaban. Rivaroxaban was shown to decrease thrombin generation, resulting in less TAFI activation, thus enhancing lysis. These effects were also shown to be less substantial in the presence of greater TAFI levels or the more stable Ile325 enzyme. These findings suggest a role for TAFI levels and the Thr325Ile polymorphism in the pharmacodynamics and pharmacogenomics of rivaroxaban.

EMS Use and Success Rates of Intraosseous Infusion for Pediatric Resuscitations: A Large Regional Health System Experience.

OBJECTIVE: Access of intraosseous (IO) compartments is a commonly used technique that is an invaluable asset in emergency resuscitation. Prehospital IO success rates using semi-automatic insertion devices vary between 70 and 100% of pediatric patients. There are limited data on time to insertion and duration of IO function in the prehospital setting. Recent studies limited to the pediatric emergency department (PED) setting have also suggested that IOs may be less successful in the infant population. We explored the use of IO access for pediatric resuscitation, encompassing the prehospital and pediatric emergency department (PED) settings. METHODS: This is a retrospective review of emergency medical services (EMS) patient care reports and PED data of patients aged 0-17 years old and transported by regional ground EMS agencies in Southwestern Ontario, Canada from 2012 to 2019. Mean and median time to first insertion and IO function (from insertion to IO failure, IV access, transfer to ICU, or death) were calculated. RESULTS: Successful prehospital IO access was achieved in 83.7% of patients. The median time required to achieve IO access was 4 min (IQR 3-7) and mean duration of IO function was 27.6 min (SD: 14.8). Patients less than 1 year old had fewer functional IOs (25.9% vs. 75.0%), more insertion attempts (2 vs. 1), and shorter duration of IO function (18.8 vs. 32.2 mins) than the older age group (p < 0.05). CONCLUSIONS: This is the first study to provide time to IO access and IO duration in the prehospital setting, and the first prehospital evidence to suggest inferior IO function in infants <1 year old, compared to other ages. This highlights unique challenges for infants that have implications for the PED, interfacility transport, and critical care settings.