Management of dabigatran-induced bleeding: expert statement

Fugate JE, Rabinstein AA, McBane RD, Lanzino G. Dabigatran: a primer for neurosurgeons. World Neurosurg. 2012 Jun 19. doi:pii:S1878–8750(12)00639-0. 10.1016/j.wneu.2012.06.019 (Epub ahead of print).

Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American college of chest physicians antithrombotic therapy and prevention of thrombosis panel. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: american college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(Suppl 2):7S–47S. PubMedCrossRef

Kozek-Langenecker S, Afshari S, Albaladejo P, Santullano CA, De Robertis E, Filipescu D, Fries D, Görlinger K, Haas T, Imberger G, Jacob M, Lancé M, Llau J, Mallett S, Meier J, Rahe-Meyer N, Samama CM, Smith A, Solomon C, Van der Linden P, Wikkelsø A, Wouters P, Wyffels P. Guidelines on the management of severe perioperative bleeding. Eur J Anaesthesiol. 2013;30(6):270–382. PubMedCrossRef

Weltermann A, Brodmann M, Domanovits H, Eber B, Gottsauner-Wolf M, Halbmayer WM, Hiesmayr JM, Kyrle PA, Längle F, Roithinger FX, Watzke H, Windhager R, Wolf C, Zweiker R. Dabigatran in patients with atrial fibrillation: perioperative and periinterventional management. Wien Klin Wochenschr. 2012;124(9–10):340–7. PubMedCrossRef

Cheng JW, Vu H. Dabigatran etexilate: an oral direct thrombin inhibitor for the management of thromboembolic disorders. Clin Ther. 2012;34(4):766–87. PubMedCrossRef

Kreutz R. Pharmakologie neuer oraler Antikoagulantien. Grundlage für rationale Entscheidungen. Klinikarzt. 2012;41(S1):10–5.

Spannagl M, Bauersachs E, Debus ES, Gawaz M, Gerlach H, Haas S, Hach-Wunderle V, Lindhoff-Last E, Riess H, Schellong S, Schinzel H, Bode C. Therapie mit Dabigatran—Periinterventionelles Management und Interpretation von Gerinnungstests. Hämostaseologie. 2012;32:294–305. PubMedCrossRef

www.​akdae.​de; Leitfaden der Arzneimittelkommission der deutschen Ärzteschaft. Orale Antikoagulation bei nicht valvulärem Vorhofflimmern. Empfehlungen zum Einsatz der neuen Antikoagulantien Dabigatran (Pradaxa) und Rivaroxaban (Xarelto). Version 1.0, September 2012.

Samama CM. New anticoagulants: pharmacology and clinical studies. Wien Med Wochenschr. 2011;161(3–4):54–7. PubMedCrossRef

Stangier J, Rathgen K, Stähle H, Gansser D, Roth W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral 2 thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol. 2007;64(3):292–303. PubMedCrossRef

Sauer H, Wankmüller H, Leschke M. Blutungsmanagement, perioperatives und periprozedurales Bridging: Vorschlag praktischer Strategien für die neuen oralen Antikoagulantien. Klinikarzt. 2012;41:26–32. CrossRef

Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, RE-LY steering committee and investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–51. PubMedCrossRef

Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P, ESC Committee for Practice Guidelines (CPG), Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, Document Reviewers, Vardas P, Al-Attar N, Alfieri O, Angelini A, Blömstrom-Lundqvist C, Colonna P, De Sutter J, Ernst S, Goette A, Gorenek B, Hatala R, Heidbüchel H, Heldal M, Kristensen SD, Kolh P, Le Heuzey JY, Mavrakis H, Mont L, Filardi PP, Ponikowski P, Prendergast B, Rutten FH, Schotten U, van Gelder IC, Verheugt FW. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–47. PubMedCrossRef

Halbmayer WM, Weigel G, Quehenberger P, et al. Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests. Clin Chem Lab Med. 2012;50(9):1601–5. doi:10.1515/cclm-2011–0888. PubMedCrossRef

Lindahl TL, Baghaei F, Blixter IF, Gustafsson KM, Stigendal L, Sten-Linder M, Strandberg K, Hillarp A, Expert group on coagulation of the external quality assurance in Laboratory Medicine in Sweden. Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays. Thromb Haemost. 2011;105(2):371–8. PubMedCrossRef

Omran H, Bauersachs R, Rübenacker S, Goss F, Hammerstingl C. The HAS-BLED score predicts bleedings during bridging of 2 oral anticoagulation. Results from the national multicentre BNK Online bridging registry (BORDER). Thromb Haemost. 2012;108(1):65–73. PubMedCrossRef

Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137(2):263–72. PubMedCrossRef

Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368(8):709–18. PubMedCrossRef

Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361:2342–52. PubMedCrossRef

Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements 2 critical care. Transfusion requirements in critical care investigators, canadian critical care trials group. N Engl J Med. 1999;340(6):409–17. PubMedCrossRef

Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, Hunt BJ, Komadina R, Nardi G, Neugebauer E, Ozier Y, Riddez L, Schultz A, Stahel PF, Vincent JL, Spahn DR, Task force for advanced bleeding care in trauma. Management of bleeding following major trauma: an updated European guideline. Crit Care. 2010;14(2):R52. PubMedCrossRef

Fries D, Innerhofer P, Perger P, Gütl M, Hofmann N, Kneifel W, Neuner L, Pernerstorfer T, Pfanner G, Schöchl H, Ziegler B, Kölblinger C, Kozek-Langenecker SA. Gerinnungsmanagement bei traumatisch bedingter Massivblutung. AINS. 2010;45:552–61. PubMed

Cotton BA, McCarthy JJ, Holcomb JB. Acutely injured patients on dabigatran. N Eng J Med. 2011;365:2038–40. CrossRef

Weitz JI, Quinlan DJ, Eikelboom JW. Periprocedural management and approach to bleeding in patients taking dabigatran. Circulation. 2012;126(20):2428–32. PubMedCrossRef

Pezborn E, Trabandt A, Selbach K, Tinel H. Prothrombin complex concentrate reverses the effects of high-dose rivaroxaban in rats (Abstract). Pathophysiol Haemost Thromb. 2010;37:A10–OC251.

van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A. Dabigatran etexilate—a novel, reversible. oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116–27. PubMedCrossRef

Eerenberg ES. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate. Circulation. 2011;124:1573–9. PubMedCrossRef

Baron TH, Kamath PS, McBane RD. Management of anithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013;368:2113–24. PubMedCrossRef

Kozek-Langenecker S, Sorensen B, Hess J, Spahn DR. Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review. Critical Care. 2011;15:R239. PubMedCrossRef

Abdel-Wahab O, Healy B, Dzik W. Effect of fresh frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion. 2006;46:1279–85. PubMedCrossRef

Ortel TL. Perioperative management of patients on chronic antithrombotic therapy. Hematology Am Soc Hematol Educ Program. 2012;2012:529–35. PubMed

Goodnough LT, Shander A. Special article: current status of pharmacologic therapies. Anesth Analg. 2013;116:15–34. PubMedCrossRef

Regionalanästhesie unter gerinnungshemmender Medikation. Empfehlungen der Arbeitsgruppe perioperative Gerinnung der ÖGARI. http://​www.​oegari.​at/​web_​files/​dateiarchiv/​116/​Regionalanästhes​ie%20​und%20​Gerinnungshemmer​%20​2013.​pdf. Last access 24 Sep 2013.

Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau J, Samama M. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol. 2010;27:999–1015. PubMedCrossRef

Afshari A, Wikkelsø A, Brok J, Møller AM, Wetterslev J. Thrombelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion. Cochrane Database Syst Rev. 2011;(3):CD007871. doi:10.1002/14651858.CD007871.