Managing patients on direct factor Xa inhibitors with rapid thrombelastography

Abstract

The use of direct factor Xa inhibitors rivaroxaban and apixaban (XABANs) has rapidly increased; however, there is no validated test available to monitor the effect on hemostasis. This study aims to assess how hemostatic management based on the Rapid Thromboelastography (R-TEG) variable activated clotting time (ACT) of XABAN patients with ongoing bleedings or in need for acute surgical intervention, affected patient outcome. A total of 343 XABAN patients were included in the main analysis together with 50 healthy volunteers to validate the reference value for ACT. An ACT >120 s (s) was defined as having XABAN-induced coagulopathy. Sixty-five percent of the XABAN patients presented with R-TEG ACT within the normal reference. Patients with XABAN-induced coagulopathy had a significantly increased risk of severe bleeding. Significantly more patients with extra-cerebral bleeding (ECB) and ACT above 120 s were transfused with five red blood cell (RBC) units or more compared to patients with ACT at 120 s or below (17% vs. 3%, p <.05). Significantly more XABAN-patients with ACT above 120 s received pro-hemostatic intervention with prothrombin complex concentrate (PCC) when compared to those with ACT at 120 s or below (ECB: 2% vs. 8%, p =.03, intracranial hemorrhage: 25% vs. 68%, p <.00). Patients who received PCC had a higher 30- and 90-day mortality compared to the rest of the cohort (16% vs. 6%, p = .02 and 21% vs. 7%, p =.00). Patients with XABAN-induced coagulopathy as evaluated by R-TEG ACT presented with more severe bleeding and higher transfusion requirements when compared to those with ACT in the normal range. This suggests that R-TEG ACT measurement in XABAN patients with active hemorrhage or in need for acute surgery may be of clinical value.

Keywords: Anticoagulants; apixaban; drug monitoring; hemorrhage; hemostatics; rivaroxaban; thrombelastography.