A prospective observational study of the rapid detection of clinically-relevant plasma direct oral anticoagulant levels following acute traumatic injury

Abstract

In urgent clinical situations, such as trauma, urgent surgery or before thrombolysis, rapid quantification of direct oral anticoagulant plasma drug levels is warranted. Using the ClotPro® analyser, we assessed two novel viscoelastic tests for detection of clinically-relevant plasma drug levels in trauma patients. The ecarin clotting time was used to assess the plasma concentration of dabigatran and Russell´s viper venom clotting time to determine the plasma concentration of direct factor Xa inhibitors. In parallel, plasma concentrations were analysed using plasma-based chromogenic assays. A total of 203 simultaneous measurements were performed. Strong to very strong linear correlations were detected between ecarin clotting time and plasma concentration of dabigatran (r = 0.9693), and between Russell´s viper venom clotting time and plasma concentrations of apixaban (r = 0.7391), edoxaban (r = 0.9251) and rivaroxaban (r = 0.8792), all p < 0.001. An ecarin clotting time ≥ 189 seconds provided 100% sensitivity and 90% specificity for detecting plasma dabigatran concentrations ≥ 50 ng.ml^-1 . Corresponding Russell´s viper venom clotting time cut-off values were ≥ 136 seconds for apixaban (80% sensitivity, 88% specificity), ≥ 168 seconds for edoxaban (100% sensitivity, 100% specificity) and ≥ 177 seconds for rivaroxaban (90% sensitivity, 100% specificity). Detection of drug levels ≥ 100 ng.ml^-1 was also investigated: for dabigatran, an ecarin clotting time ≥ 315 seconds yielded 92% sensitivity and 100% specificity; while Russell´s viper venom clotting time cut-offs of 191, 188 and 196 seconds were calculated for apixaban (67% sensitivity, 88% specificity), edoxaban (100% sensitivity, 75% specificity) and rivaroxaban (100% sensitivity, 91% specificity), respectively. We have demonstrated strong positive correlations between plasma drug levels and clotting time values in the specific ClotPro assays. Cut-off values for detecting clinically-relevant drug levels showed high levels of sensitivity and specificity.

Keywords: ClotPro; ECA-test; RVV-test; direct oral anticoagulant.