Idarucizumab is a specific antagonist for dabigatran etexilate (DE). The recent market authorization of idarucizumab in Europe and the USA may reassure prescribers of DE, as it can increase the safety of the emergency management of patients taking this anticoagulant. However, idarucizumab use should be limited to specific indications to avoid unnecessary risks to patients and costs to healthcare systems. Areas covered: The authors provide an overview of idarucizumab development and its pharmacokinetic and pharmacodynamic properties. The results of the clinical phase III trial RE-VERSE AD and a review of recent case reports of idarucizumab use in emergency contexts are also discussed. Expert opinion: Although idarucizumab has shown clear efficacy in reversing dabigatran-induced coagulopathy, its overall effects on patient outcome have not been proven. Information regarding the clinical context in which patients on DE are admitted for emergency treatment, and accurate laboratory tests of dabigatran plasma level during reversal may inform selection and help with the follow-up of patients who may benefit from idarucizumab. Idarucizumab should be integrated into protocol for the emergency management of patients on DE. Furthermore, the benefit of idarucizumab in specific indications such as acute ischemic stroke should be investigated.

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IntroductionEstimation of residual apixaban plasma concentrations may be requested in the management of emergencies. This study aims at assessing the performance of specific anti‐Xa assays calibrated with apixaban on real‐life samples with low apixaban plasma concentrations (<30 ng/mL) and on‐treatment ranges, with and without interference of low‐molecular‐weight heparin (LMWH).MethodsThe performance of the STA®‐Liquid Anti‐Xa assay (STA® LAX) and the low and normal procedures of the Biophen®Direct Factor Xa Inhibitors (DiXaI) assay was tested on 134 blood samples, collected from patients on apixaban, wherefrom 74 patients received LMWH after apixaban cessation. The results were compared with the liquid chromatography coupled with tandem mass spectrometry (LC‐MS/MS) measurements.ResultsThe Biophen®DiXaI, Biophen®DiXaI LOW, and STA®LAX showed very good correlation with LC‐MS/MS measurements in patients without LMWH administration (Spearman r .95, .99, and .98, respectively). Their limits of quantitation were defined at 48, 24, and 12 ng/mL, respectively. The Bland‐Altman test measured mean bias (SD) at 5.6 (13.1), −2.5 (5.0), and −0.8 (6.1) ng/ml, respectively. The Spearman r of the Biophen®DiXaI decreased to 0.64 in presence of low apixaban concentrations. The Spearman r of the Biophen®DiXaI LOW and STA®LAX decreased to 0.39 and 0.26, respectively, in presence of LMWH.ConclusionsThe accuracy of the low methodologies (Biophen®DiXaI LOW and STA®LAX) is slightly improved for low apixaban plasma concentrations, compared with the normal procedure of Biophen®DiXaI. The interference of LMWH on the low methodologies is measurable, however, less important than the previously reported interference of LMWH on rivaroxaban calibrated specific anti‐Xa assays.

Direct oral anticoagulants (DOAC) are used in several indications for the prevention and treatment of thrombotic events. As highlighted by data from clinical trials and case studies, all DOAC carry the risk of bleeding despite careful selection and patient management. Previous publications have demonstrated the limited knowledge of many physicians concerning the indications for, and correct management of, these anticoagulants. Health institutions should develop risk minimisation strategies and educational materials to prevent major adverse events related to DOAC administration. Major bleeding events are reported in clinical practice and specific antidotes are emerging from Phase III trials. Some antidotes are licensed but their high cost might limit routine use. We therefore illustrate approaches and tools that can help physicians prescribe DOAC appropriately. We focus on screening for modifiable bleeding risk factors and adapting doses according to the individual benefit-risk profile. We also provide recommendations on managing a missed dose, switching, bridging, and resumption.