Abstract
Background: Idarucizumab has been included in guidelines for the management of bleeding or surgical procedure in dabigatran-treated patients without need for biological monitoring. The aim of the study was to assess the prognostic value of dabigatran plasma level before reversal to test the hemostatic efficacy of idarucizumab. The secondary objectives were (i) to analyze plasma dabigatran level according to the risk of rebound and (ii) to evaluate the incidence of post-reversal non-favorable clinical outcomes (including thromboembolism, bleeding, antithrombotic, and death) and antithrombotic resumption.Methods and Results: This was an observational multicentric cohort study, which included all French patients who required idarucizumab for dabigatran reversal. Between May 2016 and April 2019, 87 patients from 21 French centers were enrolled. Patients received idarucizumab for overt bleeding (n = 61), urgent procedures (n = 24), or overdose without bleeding (n = 2). Among patients with major bleeding (n = 57), treatment with idarucizumab was considered effective in 44 (77.2%) of them. Patients who did not achieve effective hemostasis after reversal had a significantly higher mean level of plasma dabigatran at baseline (524.5 ± 386 vs. 252.8 ng/mL ± 235, p = 0.033). Furthermore, patients who did not achieve effective hemostasis after reversal had less favorable outcomes during follow-up (46.2 vs. 81.8%, p = 0.027). ROC curve identified a cutoff of 264 ng/mL for dabigatran level at admission to be predictive of ineffective hemostasis. No plasma dabigatran rebound was observed after reversal in patients with dabigatran plasma level < 264 ng/mL at baseline.Conclusion: This retrospective study shows that dabigatran level before reversal could predict hemostatic effectiveness and dabigatran plasma rebound after idarucizumab injection.
Highlights
The specific reversal agent idarucizumab is a humanized monoclonal antibody fragment that binds dabigatran with a very high affinity
When classifying major bleeding patients according to renal function, we found that renal impairment was associated with increased baseline dabigatran level (Table 3), effective hemostasis did not correlate with Creatinine clearance (CrCl) (p = 0.23) nor with the distribution of renal function into four groups (p for trend test 0.12 and p for Pearson’s chi-squared test 0.48)
For patients with major bleeding, the highest likelihood ratio corresponded to a plasma dabigatran ≥264 ng/mL, which was a predictor of ineffective hemostasis, with an area under the receiver operating characteristic (ROC) curve of 0.729
Summary
The specific reversal agent idarucizumab is a humanized monoclonal antibody fragment that binds dabigatran with a very high affinity. The RE-VERSE AD trial [1] showed the efficacy and safety of idarucizumab to reverse the anticoagulant effect of dabigatran within 4 h after its administration in dabigatran-treated patients who experienced serious bleeding or required urgent invasive procedures. A German national retrospective study [6] enrolled 120 dabigatran-treated patients who received idarucizumab, 80 of whom with ischemic stroke and 40 with intracranial bleeding (ICH in 27 patients). Idarucizumab has been included in guidelines for the management of bleeding or surgical procedure in dabigatran-treated patients without need for biological monitoring. The secondary objectives were (i) to analyze plasma dabigatran level according to the risk of rebound and (ii) to evaluate the incidence of post-reversal non-favorable clinical outcomes (including thromboembolism, bleeding, antithrombotic, and death) and antithrombotic resumption
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