Abstract 18544: Bloods Loss in Dabigatran Anticoagulated Pigs With Polytrauma is Significantly Reduced by Early Therapy With Activated and Non-activated Prothrombin Complex Concentrates
Introduction: The reversal of the new oral anticoagulants in severely bleeding patients with prothrombin complex concentrates remains uncertain with conflicting evidence. This study assessed the ability of a four-factor PCC and activated PCC (aPCC) to reverse dabigatran anticoagulation in a porcine polytrauma model.
Methods: After ethical approval, male pigs (n=30) were given dabigatran etexilate for 3 days (30 mg/kg bid PO), the sham group (n=6) received placebo. To accomplish supratherapeutic anticoagulation, dabigatran was infused for 90 min (30 min: 0.77 mg/kg/h; 60 min 0.52 mg/kg/min) prior to injury on day 4 in anaesthetized pigs. A standardized blunt liver injury and bilateral femur fractures were induced. Following hemorrhagic shock, resuscitation was started 5 min after trauma and blood loss (BL) was recorded 12 min post trauma. Randomized animals (n=6/group) received a single injection of PCC or aPCC (25 and 50 IU/kg), or vehicle (control). BL and hemodynamic variables were monitored over 5 h or until time of death. Data were analyzed by ANOVA (± SD).
Results: After infusion and prior to injury dabigatran levels were 559 ± 36 ng/mL and remained elevated throughout. In contrast to sham animals (BL: 601 ± 137 mL), BL in in all anticoagulated animals was significantly elevated 12 min post injury (BL : 791 ± 54 mL). Anticoagulation with dabigatran without PCC therapy resulted in a total BL of 3774 ± 628 mL) with 100% mortality (survival time: 65-146 min; p<0.05 vs PCC/aPCC 50 IU/kg treated animals). Although the onset of bleeding was reduced in animals receiving 25 IU/kg PCC or aPCC, total BL (PCC: 3679 ± 782 mL; aPCC: 3638 ± 474 mL) was similar to control animals. In contrast, application of 50 IU/kg PCC (1767 ± 135 mL) or aPCC (1647 ± 302 mL) showed a significant reduction in total BL with 100% survival.
Conclusions: This porcine model demonstrates that high doses of PCC and aPCC application of PCC may be a reasonable intervention for dabigatran-treated patients with life-threatening haemorrhage, though these data need clinical confirmation.
Author Disclosures: O. Grottke: Research Grant; Significant; Boehringer Ingelheim, CSL Behring. Other Research Support; Significant; Novo Nordisk, Biotest, Nycomed. Honoraria; Significant; Boehringer Ingelheim, CSL Behring. Consultant/Advisory Board; Significant; Boehringer Ingelheim, CSL Behring, Novo Nordisk. M. Honickel: Honoraria; Significant; Boehringer Ingelheim. J. van Ryn: Employment; Significant; Boehringer Ingelheim. H. ten Cate: Research Grant; Significant; Boehringer Ingelheim. H. Spronk: Research Grant; Significant; Boehringer Ingelheim. Honoraria; Significant; Bayer Healthcare. R. Rossaint: Honoraria; Significant; Novo Nordisk. Consultant/Advisory Board; Significant; CSL Behring.
- © 2014 by American Heart Association, Inc.