Reversal of dabigatran by intraosseous or intravenous idarucizumab in a porcine polytrauma model.

ABSTRACT

BACKGROUND: Idarucizumab is licensed to reverse dabigatran in life-threatening haemorrhage. Establishment of venous access can be challenging, and the intraosseous (IO) route is a potentially life-saving alternative. In this study, we compared the efficacy and safety of IO or intravenous (i.v.) idarucizumab for dabigatran reversal in a porcine polytrauma model. METHODS: Male pigs (n=21) received oral dabigatran etexilate (30 mg kg-1 bid) for 3 days. On the 4th day, animals received dabigatran infusion and were randomised 111 to receive IO saline (control), i.v. idarucizumab (60 mg kg-1), or IO idarucizumab (60 mg kg-1), or animals were included in a sham group (n=7). Study treatment was administered after polytrauma and the animals were monitored for 240 min, or until death. Coagulation status was monitored by thromboelastometry, thromboelastography, and thrombin measurements. RESULTS: Total blood loss was lowest in sham animals [521 (52) ml, P<0.01 vs all other groups], and comparable in the two idarucizumab groups [IO 1085 (102) ml vs i.v. 1142 (125) ml], and highest in the control group [4065 (557) ml, P<0.001 vs all other groups]. Survival to 240 min was 100% in the sham group and both idarucizumab groups, and 14% in the control group. IO and i.v. idarucizumab promptly normalised global coagulation assays and thrombin generation. Thromboelastography showed a strong correlation between dabigatran concentrations and R-time (R2=0.90 and 0.89) in idarucizumab-treated animals. CONCLUSIONS: Intravenous and intraosseous idarucizumab were comparable for reversing dabigatran in a porcine trauma model. Dabigatran reversal could be monitored using fully automated thromboelastography.