Adsorption of dabigatran in plasma samples containing the drug neutralizes its activity as efficiently as the addition of idarucizumab. This method allows the evaluation of thrombophilia markers without interruption of anticoagulation therapy or the detection of hemostasis disorders in patients treated with the drug.

To cite this article: Jacquemin M, Toelen J, Schoeters J, van Horenbeeck I, Vanlinthout I, Debasse M, Peetermans M, Vanassche T, Peerlinck K, van Ryn J, Verhamme P. The addition of idarucizumab to plasma samples containing dabigatran allows the use of routine coagulation assays for the diagnosis of hemostasis disorders. J Thromb Haemost 2015; 13: 2087-92.Summary. Background: The anticoagulant effect of dabigatran can be approximated by its prolongation of routine coagulation assays. Consequently, dabigatran also interferes with thrombophilia screening or with diagnosing hemostasis disorders that have developed after the initiation of anticoagulant treatment, such as vitamin K deficiency or acquired hemophilia A. Objectives: This study was carried out to determine whether idarucizumab, a humanized antibody fragment that binds dabigatran, could fully neutralize dabigatran in routine diagnostic coagulation assays conducted in vitro, thereby preventing false-positive or false-negative diagnostic readouts. Methods: Preliminary experiments identified coagulation assays that were sensitive to dabigatran, and identified a concentration of idarucizumab that neutralized the effects of dabigatran. These assays were then carried out with patient and control plasma samples spiked with dabigatran, with or without a molar excess of idarucizumab. Results: Dabigatran altered the prothrombin time, activated partial thromboplastin time and thrombin time, and the measurement of intrinsic and extrinsic factor levels. Screening and confirmation tests used for lupus anticoagulant detection were prolonged by dabigatran, falsely suggesting the presence of lupus anticoagulant. Conversely, the addition of dabigatran falsely corrected an abnormal activated protein C resistance ratio. Addition of idarucizumab completely normalized these measurements, and allowed the correct identification of normal and abnormal samples with these assays. Conclusions: In vitro addition of idarucizumab to plasma samples containing dabigatran fully neutralizes the drug, and facilitates the use of routine coagulation assays to allow the diagnosis of hemostasis disorders that may be concurrently present in patients taking dabigatran.

Background-The effects of alteplase (rtPA), streptokinase, and staphylokinase (rSak) on focal cerebral ischemia (FCI) and on pulmonary clot lysis (PCL) were studied in hamsters. Methods and Results-FCI was produced by ligation of the left middle cerebral artery (MCA) and common carotid artery (CCA) and a 10-minute occlusion of the right CCA. FCI was measured after 24 hours by 2,3,5-triphenyltetrazolium chloride staining. 125 I-fibrin-labeled plasma clots were injected via the jugular vein, and clot lysis was determined from residual radioactivity at 90 minutes. Study drugs were given intravenously over 60 minutes. FCI increased from 1.2 (0.27 to 2.3) mm 3 (median and 17th to 83rd percentile range, nϭ24) in controls to 19 to 27 mm 3 with thrombolytic agent, with maximal rates at 0.13Ϯ0.05 mg/kg rtPA, 0.23Ϯ0.09 mg/kg streptokinase, and 0.037Ϯ0.025 mg/kg rSak. PCL increased from 18Ϯ2% (meanϮSEM, nϭ27) in controls to Ϸ85% with thrombolytics, with maximal rates at 0.12Ϯ0.03 mg/kg rtPA, 0.17Ϯ0.05 mg/kg streptokinase, and 0.018Ϯ0.002 mg/kg rSak. All agents caused maximal FCI and PCL rates at similar doses without ␣ 2 -antiplasmin and fibrinogen depletion. Injection of 6 mg/kg human plasminogen combined with streptokinase caused a "systemic fibrinolytic state" with fibrinogen depletion. Maximal rates of FCI were obtained with 0.097Ϯ0.077 mg/kg streptokinase (Pϭ0.26 versus streptokinase alone) and of PCL with 0.010Ϯ0.002 mg/kg (Pϭ0.006 versus streptokinase alone). Conclusions-Thrombolytic