XXXIII Congreso Nacional de la Sociedad Española de Trombosis y Hemostasia

Ponencias 29 fessionals is also key, and it should include appropriate instructions for detecting and reporting adverse reactions, with all patients receiving contact information of the prescribing clinic. The task force also found crucial that clinicians and patients understand that rapid reversal of anticoagulation is not sufficient per se to solve bleeding until the source of bleeding has been adequately treated. Thus, the management of bleeding should never only rely on the use of a reversal agent. Conclusions Indeed, more information is still needed on the efficacy and safe- ty of reversal agents, given the limited number of patients currently enrolled in phase III clinical trials. The lack of a control group in these studies also contributes to limit our understanding of their efficacy. For this reason, all clinicians involved in the management of antico- agulated patients and in the emergency setting should try to contribute to registries when using these reversal agents, and more in general, when managing severe complications in patients on DOACs with the aim to improve our knowledge. References 1. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, 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;383:955-62. 2. Van Es N, CoppensM, Schulman S, Middeldorp S, et al. Direct oral anti- coagulants comparedwith vitaminK antagonists for acute venous throm- boembolism: evidence from phase 3 trials. Blood 2014;124:1968-75. 3. Graham DJ, Reichman ME, Wernecke M, Zhang R, et al. Cardiovas- cular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation 2015;131:157-64. 4. Larsen TB, Rasmussen LH, Skjøth F, Due KM, et al. Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol 2013;61:2264-73. 5. Beyer-Westendorf J, Ebertz F, Förster K, Gelbricht V, et al. Effective- ness and safety of dabigatran therapy in daily-care patients with atrial fibrillation. Results from the Dresden NOACRegistry. Thromb Haemost 2015;113:1247-57. 6. Larsen TB, Gorst-RasmussenA, Rasmussen LH, Skjoth F, et al. Bleed- ing events among new starters and switchers to dabigatran compared with warfarin in atrial fibrillation. Am J Med 2014;127:650-6. 7. Hernandez I, Baik SH, PiñeraA, ZhangY. Risk of bleeding with dabig- atran in atrial fibrillation. JAMA Intern Med 2015;175:18-24. 8. Beyer-Westendorf J, Förster K, Pannach S, Ebertz F, et al. Rates, man- agement, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014;124:955-62. 9. Olesen JB, Sørensen R, Hansen ML, Lamberts M, et al. Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naïve atrial fibrillation patients: Danish nationwide descriptive data 2011-2013. Europace 2015;17:187-93. 10. CammAJ, Amarenco P, Haas S, Hess S, et al. XANTUS: a real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation. Eur Heart J 2016;37:1145-53. 11. AgenoW, Mantovani LG, Haas S, Kreutz R, et al. Safety and effective- ness of oral rivaroxaban versus standard anticoagulation for the treat- ment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study. Lancet Haematol 2016;3:e12-21. 12. Chai-Adisaksopha C, Crowther M, Isayama T, LimW. The impact of bleeding complications in patients receiving target-specific oral anticoagulants: a systematic review and meta-analysis. Blood 2014;124:2450-8. 13. Siegal DM. Managing target-specific oral anticoagulant associated bleeding including an update on pharmacological reversal agents. J Thromb Thrombolysis 2015;39:395-402. 14. Heidbuchel H,Verhamme P,AlingsM,AntzM, et al. Updated European Heart RhythmAssociation Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with non-valvular atrial fibril- lation. Europace 2015:17:1467-507. 15. Siegal DM, Garcia DA, Crowther MA. How I treat target-specific oral anticoagulant-associated bleeding. Blood 2014;123:1152-8. 16. Glund S, Stangier J, Schmohl M, Gansser D et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-con- trolled, double-blind phase 1 trial. Lancet 2015;386:680-90. 17. Glund S, Moschetti V, Norris S, Stangier J, et al. A randomised study in healthy volunteers to investigate the safety, tolerability and pharma- cokinetics of idarucizumab, a specific antidote to dabigatran. Thromb Haemost 2015;113:943-51. 18. Glund S, Stangier J, van Ryn, Schmohl M, et al. Effect of age and renal function on idarucizumab pharmacokinetics and idarucizumab-me- diated reversal of dabigatran anticoagulant activity in a randomized, double-blind, crossover Phase Ib study. Clin Pharmacokinet 2016 e-pub ahead of print. 19. Pollack CV Jr, Reilly PA, Bernstein R, Dubiel R, et al. Design and rationale for RE-VERSEAD: A phase 3 study of idarucizumab, a spe- cific reversal agent for dabigatran. Thromb Haemost 2015;114:198-205. 20. Pollack CV Jr, Reilly PA, Eikelboom J, Glund S, et al. Idarucizumab for dabigatran reversal. N Engl J Med 2015;373:511-20. 21. Siegal DM, Curnutte JT, Connolly SJ, Lu G, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med 2015;373:2413-24. 22. Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 2013;19:446-51. 23. Siegal DM, Curnutte JT, Connolly SJ, Lu G, et al. Andexanet alfa for the reversal of factor Xa inhibitor activity. N Engl J Med 2015;373:2413-24. 24. Connolly SJ, Milling TJ, Eikelboom JW, Gibson CM, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2016;Epub ahead of print 25. Sullivan DW, Jr., Gad SC, Laulicht B, Bakhru S, et al. Nonclinical Safety Assessment of PER977: A Small Molecule Reversal Agent for New Oral Anticoagulants and Heparins. Int J Toxicol 2015;34:308-17. 26. Ansell JE, Bakhru SH, Laulicht BE, Steiner SS, et al. Use of PER977 to reverse the anticoagulant effect of edoxaban. N Engl J Med 2014;371:2141-2142. 27. Ansell JE, Laulicht BE, Bakhru SH, Hoffman M, et al. Ciraparantag safely and completely reverses the anticoagulant effects of low molec- ular weight heparin. Thromb Res 2016;Epub ahead of print. 28. Ageno W, Buller HR, Falanga A, Hacke W, et al. Managing reversal of direct oral anticoagulants in emergency situations. Anticoagulation Education Task Force White Paper. Thromb Haemost 2016;116:Epub ahead of print 29. Levy JH,AgenoW, Chan NC, Crowther M, et al.When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14:623-7.