Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex-vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model

• DOI: 10.1186/cc13717
• Publication Date: 2014-02-05T18:03:18Z
• Authors: Oliver Grottke; Joanne van Ryn; Henri MH Spronk; Rolf Rossaint
• Keywords: Antidote; Prothrombin complex concentrate; Thromboelastometry; Direct thrombin inhibitor; Recombinant Factor VIIa; Idarucizumab; Coagulation testing; Ex vivo; Prothrombin time

New oral anticoagulants are effective alternatives to warfarin. However, no specific reversal agents available for life-threatening bleeding or emergency surgery. Using a porcine model of trauma, this study assessed the ability prothrombin complex concentrate (PCC), activated PCC (aPCC), recombinant FVIIa (rFVIIa) and antidote dabigatran (aDabi-Fab) reverse anticoagulant effects dabigatran.Dabigatran etexilate (DE) was given orally 3 days (30 mg/kg bid) intravenously on day 4 achieve consistent, supratherapeutic concentrations dabigatran. Blood samples were collected at baseline, after DE, intravenous dabigatran, 60 minutes post-injury. U/kg), aPCC rFVIIa (90 180 μg/kg) (60 120 mg/kg) added blood ex-vivo. Coagulation by thromboelastometry, global coagulation assays diluted thrombin time.Plasma 380 ± 106 ng/ml 1423 432 administration, respectively, all parameters affected Both PCCs aDabi-Fab, but not rFVIIa, reversed thromboelastometry time. In contrast, aPTT only normalised aDabi-Fab. Plasma concentration (activity) remained elevated therapy, measureable aDabi-Fab.In conclusion, in reducing under different conditions, while aDabi-Fab fully corrected measures decreased plasma below limit detection. No significant observed with rFVIIa.