Therapy with activated prothrombin complex concentrate is effective in reducing dabigatran-associated blood loss in a porcine polytrauma model

Markus Honickel, Benjamin Maron, Joanne van Ryn, Till Braunschweig, Hugo ten Cate, Henri M. H. Spronk, Rolf Rossaint, Oliver Grottke*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

32 Citations (Web of Science)

Abstract

Clinical use of non-vitamin K antagonist oral anticoagulants is increasingly well established. However, specific agents for reversal of these drugs are not currently available. It was to objective of this study to investigate the impact of activated prothrombin complex concentrate (aPCC) on the anticoagulant effects of dabigatran in a randomised, controlled, porcine trauma model. Twenty-one pigs received oral and intravenous dabigatran, resulting in supratherapeutic plasma concentrations. Twelve minutes after injury (standardised bilateral femur fractures and blunt liver injury), animals (n=7/group) received 25 or 50 U/kg aPCC (aPCC25 and aPCC50) or placebo (control) and were followed for 5 hours. The primary endpoint was total volume of blood loss (BL). Haemodynamic and coagulation variables (prothrombin time [PT], activated partial thromboplastin time, diluted thrombin time, thrombin-antithrombin complexes, thromboelastometry, thrombin generation and D-dimers) were measured. Twelve minutes post-injury, BL was similar between groups. Compared with control (total BL: 3807 +/- 570 ml) and aPCC25 (3690 +/- 454 ml; p=0.77 vs control), a significant reduction in total BL (1639 +/- 276 ml; p
Original languageEnglish
Pages (from-to)271-284
JournalThrombosis and Haemostasis
Volume115
Issue number2
DOIs
Publication statusPublished - Feb 2016

Keywords

  • Anticoagulants
  • aPCC
  • dabigatran
  • FEIBA
  • polytrauma
  • reversal
  • idarucizumab

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