Newly Published
Critical Care Medicine  |   August 2017
Reversing Dabigatran Anticoagulation with Prothrombin Complex Concentrate versus Idarucizumab as Part of Multimodal Hemostatic Intervention in an Animal Model of Polytrauma
Author Notes
  • From the Department of Anesthesiology (M.H., R.R., C.S., O.G.) and Department of Pathology (T.B.), RWTH Aachen University Hospital, Aachen, Germany; and the Division of Clinical Thrombosis and Hemostasis, Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands (H.t.C.).
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Submitted for publication February 3, 2017. Accepted for publication June 22, 2017.
    Submitted for publication February 3, 2017. Accepted for publication June 22, 2017.×
  • Acknowledgments: The authors thank Renate Nadenau (Department of Anesthesiology, RWTH Aachen University Hospital, Aachen, Germany) and Johanna Schurer (Boehringer Ingelheim, Biberach, Germany) for excellent laboratory assistance. Joanne van Ryn, Ph.D. (Boehringer Ingelheim) is acknowledged for critical reading.
    Acknowledgments: The authors thank Renate Nadenau (Department of Anesthesiology, RWTH Aachen University Hospital, Aachen, Germany) and Johanna Schurer (Boehringer Ingelheim, Biberach, Germany) for excellent laboratory assistance. Joanne van Ryn, Ph.D. (Boehringer Ingelheim) is acknowledged for critical reading.×
  • Research Support: Supported by the START program of RWTH Aachen University (Aachen, Germany) and by Boehringer Ingelheim (Biberach, Germany).
    Research Support: Supported by the START program of RWTH Aachen University (Aachen, Germany) and by Boehringer Ingelheim (Biberach, Germany).×
  • Competing Interests: Dr. Honickel has received travel support from Boehringer Ingelheim (Ingelheim, Germany). Dr. Rossaint has received honoraria for lectures and consultancy from CSL Behring (Marburg, Germany), Boehringer Ingelheim, and Novo Nordisk (Bagsvaerd, Denmark). Dr. ten Cate has received research funding from CSL Behring, Bayer (Leverkusen, Germany), Philips (Amsterdam, Netherlands), Pfizer (Berlin, Germany), and Boehringer Ingelheim, and honoraria for lectures and consultancy from Bayer, Leo Pharma (Neu-Isenburg, Germany), Boehringer, and Pfizer. Dr. ten Cate is a consultant to Stago (Dusseldorf, Germany) and a fellow of the Gutenberg Research Foundation, Center for Thrombosis and Haemostasis (Mainz, Germany). Dr. Grottke has received research funding from Bayer, Biotest (Dreieich, Germany), Boehringer Ingelheim, CSL Behring, Novo Nordisk, and Nycomed (Zurich, Switzerland). Dr. Grottke has also received honoraria for lectures and consultancy support from Baxalta (Unterschleißheim, Germany), Bayer Healthcare, Boehringer Ingelheim, CSL Behring, Octapharma (Lachen, Switzerland), Pfizer, Portola (San Francisco, California), and Sanofi (Berlin, Germany).
    Competing Interests: Dr. Honickel has received travel support from Boehringer Ingelheim (Ingelheim, Germany). Dr. Rossaint has received honoraria for lectures and consultancy from CSL Behring (Marburg, Germany), Boehringer Ingelheim, and Novo Nordisk (Bagsvaerd, Denmark). Dr. ten Cate has received research funding from CSL Behring, Bayer (Leverkusen, Germany), Philips (Amsterdam, Netherlands), Pfizer (Berlin, Germany), and Boehringer Ingelheim, and honoraria for lectures and consultancy from Bayer, Leo Pharma (Neu-Isenburg, Germany), Boehringer, and Pfizer. Dr. ten Cate is a consultant to Stago (Dusseldorf, Germany) and a fellow of the Gutenberg Research Foundation, Center for Thrombosis and Haemostasis (Mainz, Germany). Dr. Grottke has received research funding from Bayer, Biotest (Dreieich, Germany), Boehringer Ingelheim, CSL Behring, Novo Nordisk, and Nycomed (Zurich, Switzerland). Dr. Grottke has also received honoraria for lectures and consultancy support from Baxalta (Unterschleißheim, Germany), Bayer Healthcare, Boehringer Ingelheim, CSL Behring, Octapharma (Lachen, Switzerland), Pfizer, Portola (San Francisco, California), and Sanofi (Berlin, Germany).×
  • Correspondence: Address correspondence to Dr. Grottke: Department of Anesthesiology, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany. ogrottke@ukaachen.de.Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Critical Care Medicine / Coagulation and Transfusion / Critical Care
Critical Care Medicine   |   August 2017
Reversing Dabigatran Anticoagulation with Prothrombin Complex Concentrate versus Idarucizumab as Part of Multimodal Hemostatic Intervention in an Animal Model of Polytrauma
Anesthesiology Newly Published on August 31, 2017. doi:10.1097/ALN.0000000000001856
Anesthesiology Newly Published on August 31, 2017. doi:10.1097/ALN.0000000000001856
Abstract

Background: Although idarucizumab is the preferred treatment for urgent dabigatran reversal, it is not always available. Prothrombin complex concentrate (PCC) may be an alternative and, with bleeding in trauma, additional hemostatic therapy may be required. The authors investigated multimodal treatment in a preclinical polytrauma model.

Methods: Dabigatran etexilate (30 mg/kg twice daily) was given orally to 45 male pigs for 3 days. On day 4, animals received a dabigatran infusion before blunt liver injury and bilateral femur fractures. After injury, animals were randomized 1:1:1:1:1 to receive placebo (control), tranexamic acid (TXA; 20 mg/kg) plus human fibrinogen concentrate (FCH; 80 mg/kg) (TXA–FCH group), PCC (25 U/kg or 50 U/kg) plus TXA plus FCH (PCC25 and PCC50 groups), or 60 mg/kg idarucizumab (IDA) plus TXA plus FCH (IDA group). Animals were monitored for 240 min after trauma, or until death.

Results: The degree of injury was similar in all animals before intervention. Control and TXA–FCH animals had the highest total postinjury blood loss (3,652 ± 601 and 3,497 ± 418 ml) and 100% mortality (mean survival time 96 and 109 min). Blood loss was significantly lower in the PCC50 (1,367 ± 273 ml) and IDA (986 ± 144 ml) groups, with 100% survival. Thrombin–antithrombin levels and thrombin generation were significantly elevated in the PCC50 group.

Conclusions: Idarucizumab may be considered the optimal treatment for emergency reversal of dabigatran anticoagulation. However, this study suggests that PCC may be similarly effective as idarucizumab and could therefore be valuable when idarucizumab is unavailable.