Reversal of dabigatran by idarucizumab: when and how?

References

• van Es N, Coppens M, Schulman S, et al. Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials. Blood. 2014;124(12):1968–1975.
   PubMed Web of Science ®Google Scholar
• Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. 2014;383(9921):955–962.
   PubMed Web of Science ®Google Scholar
• Graham DJ, Reichman ME, Wernecke M, et al. Cardiovascular, bleeding, and mortality risks in elderly medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation. 2015;131(2):157–164.
   PubMed Web of Science ®Google Scholar
• Healey JS, Eikelboom J, Douketis J, et al. Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the randomized evaluation of long-term anticoagulation therapy (RE-LY) randomized trial. Circulation. 2012;126(3):343–348.
   PubMed Web of Science ®Google Scholar
• Beyer-Westendorf J, Gelbricht V, Forster K, et al. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective dresden NOAC registry. Eur Heart J. 2014;35(28):1888–1896.
   PubMed Web of Science ®Google Scholar
• Weitz JI, Pollack CV Jr. Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants. Thromb Haemost. 2015;114(6):1113–1126.
   PubMed Web of Science ®Google Scholar
• Siegal DM. Managing target-specific oral anticoagulant associated bleeding including an update on pharmacological reversal agents. J Thromb Thrombolysis. 2015;39(3):395–402.
   PubMed Web of Science ®Google Scholar
• Heidbuchel H, Verhamme P, Alings M, et al. Updated European heart rhythm association practical guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace. 2015;17(10):1467–1507.
   PubMed Web of Science ®Google Scholar
• Praxbind Summary of Product Characteristics [Internet]. Boehringer ingelheim. 2015 [cited 2016 May]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003986/WC500197462.pdf
   Google Scholar
• Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–1151.
   PubMed Web of Science ®Google Scholar
• Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost. 2009;15(Suppl 1):9S–16S.
   PubMed Web of Science ®Google Scholar
• van Ryn J, Goss A, Hauel N, et al. The discovery of dabigatran etexilate. Front Pharmacol. 2013;4:12.
   PubMed Web of Science ®Google Scholar
• Dabigatran Summary of Product Characteristics [Internet]. Boehringer ingelheim. [cited 2016 May]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf
   Google Scholar
• Diener HC, Easton JD, Granger CB, et al. Design of randomized, double-blind, evaluation in secondary stroke prevention comparing the efficacy and safety of the oral thrombin inhibitor dabigatran etexilate vs. acetylsalicylic acid in patients with embolic stroke of undetermined source (RE-SPECT ESUS). Int J Stroke. 2015;10(8):1309–1312.
   PubMed Web of Science ®Google Scholar
• Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342–2352.
   PubMed Web of Science ®Google Scholar
• Schulman S, Kakkar AK, Schellong SM, et al. A randomized trial of dabigatran versus warfarin in the treatment of acute venous thromboembolism (RE-COVER II). Blood. 2011;118(21):95–96.
   Web of Science ®Google Scholar
• Majeed A, Hwang HG, Connolly SJ, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013;128(21):2325–2332.
   PubMed Web of Science ®Google Scholar
• Werth S, Breslin T, NiAinle F, et al. Bleeding risk, management and outcome in patients receiving non-VKA oral anticoagulants (NOACs). Am J Cardiovasc Drugs. 2015;15(4):235–242.
   PubMed Web of Science ®Google Scholar
• Spahn DR, Bouillon B, Cerny V, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013;17(2):R76.
   PubMed Web of Science ®Google Scholar
• Schiele F, van Ryn J, Canada K, et al. A specific antidote for dabigatran: functional and structural characterization. Blood. 2013;121(18):3554–3562.
   PubMed Web of Science ®Google Scholar
• Eikelboom JW, Quinlan DJ, Van Ryn J, et al. Idarucizumab: the antidote for reversal of dabigatran. Circulation. 2015;132(25):2412–2422.
   PubMed Web of Science ®Google Scholar
• Glund S, Moschetti V, Norris S, et al. A randomised study in healthy volunteers to investigate the safety, tolerability and pharmacokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost. 2015;113(5):943–951.
   PubMed Web of Science ®Google Scholar
• Curtis BR, Swyers J, Divgi A, et al. Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets. Blood. 2002;99(6):2054–2059.
   PubMed Web of Science ®Google Scholar
• Greinacher A, Thiele T, Selleng K. Reversal of anticoagulants: an overview of current developments. Thromb Haemost. 2015;113(5):931–942.
   PubMed Web of Science ®Google Scholar
• Glund S, Stangier J, Van Ryn J, et al. Restarting dabigatran etexilate 24 h after reversal with idarucizumab and redosing idarucizumab in healthy volunteers. J Am Coll Cardiol. 2016;67(13):1654–1656.
   PubMed Web of Science ®Google Scholar
• Glund S, Stangier J, Schmohl M, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015;386(9994):680–690.
   PubMed Web of Science ®Google Scholar
• Pollack CV Jr., Reilly PA, Eikelboom J, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):511–520.
   PubMed Web of Science ®Google Scholar
• Jacquemin M, Toelen J, Schoeters J, et al. The addition of idarucizumab to plasma samples containing dabigatran allows the use of routine coagulation assays for the diagnosis of hemostasis disorders. J Thromb Haemost. 2015;13(11):2087–2092.
   PubMed Web of Science ®Google Scholar
• Grottke O, Honickel M, Van Ryn J, et al. Idarucizumab, a specific dabigatran reversal agent, reduces blood loss in a porcine model of trauma with dabigatran anticoagulation. J Am Coll Cardiol. 2015;66(13):1518–1519.
   PubMed Web of Science ®Google Scholar
• Na SY, Mracsko E, Van Ryn J, et al. Idarucizumab improves outcome in murine brain hemorrhage related to dabigatran. Ann Neurol. 2015;78(1):137–141.
   PubMed Web of Science ®Google Scholar
• Glund S, Stangier J, Schmohl M, et al. Idarucizumab, a specific antidote for dabigatran: immediate, complete and sustained reversal of dabigatran induced anticoagulation in elderly and renally impaired subjects. Blood. 2014;124(21):344.
   PubMedGoogle Scholar
• Pollack CV Jr., Reilly PA, Bernstein R, et al. Design and rationale for RE-VERSE AD: a phase 3 study of idarucizumab, a specific reversal agent for dabigatran. Thromb Haemost. 2015;114(1):198–205.
   PubMed Web of Science ®Google Scholar
• Ansell JE, Bakhru SH, Laulicht BE, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med. 2014;371(22):2141–2142.
   PubMed Web of Science ®Google Scholar
• Laulicht B, Bakhru S, Steiner S, et al. PER977 (ciraparantag) reverses edoxaban anticoagulation at steady state and has no effect on re-anticoagulation at the next scheduled dose. Eur Heart J. 2015;36:859–860.
   Web of Science ®Google Scholar
• Ghadimi K, Dombrowski KE, Levy JH, et al. Andexanet alfa for the reversal of factor Xa inhibitor related anticoagulation. Expert Rev Hematol. 2016;9(2):115–122.
   PubMed Web of Science ®Google Scholar
• Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet alfa for the reversal of factor xa inhibitor activity. N Engl J Med. 2015;373(25):2413–2424.
   PubMed Web of Science ®Google Scholar