Management of new oral anticoagulants related life threatening or major bleedings in real life: a brief report

Journal of Thrombosis and Thrombolysis

Volumn 39, Issue 4, 2015, Pages 427-433

  Masotti, Luca ^a,b   Lorenzini, Gianni ^b,c   Seravalle, Cristiana ^a   Panigada, Grazia ^d   Landini, Giancarlo ^a   Cappelli, Roberto ^e   Schulman, Sam ^f  

^a SANTA MARIA ANNUNZIATA HOSPITAL   (Italy)

^b Internal Medicine Cecina Hospital   (Italy)

^c UNIVERSITY OF PISA   (Italy)

^d Pescia Hospital   (Italy)

^e UNIVERSITY OF SIENA   (Italy)

^f MCMASTER UNIVERSITY   (Canada)

Author keywords

Bleedings; Complex concentrates; Dabigatran; Prothrombin; Rivaroxaban; Tranexamic acid

Indexed keywords

ANTICOAGULANT AGENT; ANTIFIBRINOLYTIC AGENT; BLOOD CLOTTING FACTOR; PROTHROMBIN COMPLEX CONCENTRATES; TRANEXAMIC ACID;

AGED; BLOOD; CHEMICALLY INDUCED; CLINICAL TRIAL; FEMALE; HEMORRHAGE; HUMAN; ITALY; MALE; MULTICENTER STUDY; ORAL DRUG ADMINISTRATION; VERY ELDERLY;

ADMINISTRATION, ORAL; AGED; AGED, 80 AND OVER; ANTICOAGULANTS; ANTIFIBRINOLYTIC AGENTS; BLOOD COAGULATION FACTORS; FEMALE; HEMORRHAGE; HUMANS; ITALY; MALE; TRANEXAMIC ACID;

EID: 84939889069     PISSN: 09295305     EISSN: 1573742X     Source Type: Journal    
DOI: 10.1007/s11239-014-1112-3     Document Type: Article

References (39)

1. Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ (2012) Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol 110:453–460
2. van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV (2014) Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 12:320–328
3. Ruff CT, Giugliano RP, Braunwald E et al (2013) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet. Ahead epub of print
4. Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET (2013) New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 145(105–12):e15
5. Southworth MR, Reichman ME, Unger EF (2013) Dabigatran and post-marketing reports of bleeding. N Engl J Med 368:1272–1274
6. Larsen TB, Rasmussen LH, Skjøth F, Due KM, Callréus T, Rosenzweig M, Lip GY (2013) Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol 61:2264–2273
7. Miesbach W, Seifried E (2012) New direct oral anticoagulants—current therapeutic options and treatment recommendations for bleeding complications. Thromb Haemost 108:625–632
8. Pernod G, Albaladejo P, Godier A et al (2013) Working group on perioperative haemostasis. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP)—March 2013. Arch Cardiovasc Dis 106:382–393
9. Heidbuchel H, Verhamme P, Alings M et al (2013) European Heart Rhythm Association. European Heart Rhythm Association practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15:625–651
10. Ward C, Conner G, Donnan G, Gallus A, McRae S (2013) Practical management of patients on apixaban: a consensus guide. Thromb J 11:27
11. Schulman S, Kearon C (2005) Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 3:692–694
12. Harper P, Young L, Merriman E (2012) Bleeding risk with dabigatran in the frail elderly. N Engl J Med 366:864–866
13. Harinstein LM, Morgan JW, Russo N (2013) Treatment of dabigatran-associated bleeding: case report and review of the literature. J Pharm Pract 26:264–269
14. Berger R, Salhanick SD, Chase M, Ganetsky M (2013) Hemorrhagic complications in emergency department patients who are receiving dabigatran compared with warfarin. Ann Emerg Med 61:475–479
15. Díaz MQ, Borobia AM, Núñez MA et al (2013) Use of prothrombin complex concentrates for urgent reversal of dabigatran in the Emergency Department. Haematologica 98:e143–e144
16. McDonald CJ, Kalish Ellett LM, Barratt JD, Caughey GE (2014) An international comparison of spontaneous adverse event reports and potentially inappropriate medicine use associated with dabigatran. Pharamacoepidemiol Drug Saf 2014; epub ahead of print
17. FDA Drug Safety Communication 2014 May 5. FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin
18. Beyer-Westendorf J, Forster K, Pannach S et al (2014) Rates, management and outcome of bleeding complications during rivaroxaban therapy in daily care-results from the Dresden NOAC registry. Blood; epub ahead of print
19. Desai J, Kolb JM, Weitz JI, Aisenberg J (2013) Gastrointestinal bleeding with the new oral anticoagulants-defining the issue and the management strategies. Thromb Haemost 110:205–212
20. Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W (2008) The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 36:386–399
21. Lang D, Freudenberger C, Weinz C (2009) In vitro metabolism of rivaroxaban, an oral, direct factor Xa inhibitor, in liver microsomes and hepatocytes of rats, dogs, and humans. Drug Metab Dispos 37:1046–1055
22. Heidbuchel H, Verhamme P, Alings M et al (2013) European Heart Rhythm Association. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15:625–651
23. Lega JC, Bertoletti L, Gremillet C et al (2014) Meta-embol group. consistency of safety and efficacy of new oral anticoagulants across subgroups of patients with atrial fibrillation. PLoS ONE 9:e91398
24. Fontaine GV, Mathews K, Woller SC, Lloyd JF (2014) Major bleeding with dabigatran and rivaroxaban in patients with atrial fibrillation: a real-world setting. Clin Appl Thromb Hemost; epub ahead of print
25. Baglin T, Hillarp A, Tripodi A, Elalamy I, Buller H, Ageno W (2013) Measuring oral direct inhibitors (ODIs) of thrombin and factor Xa: a recommendation from the subcommittee on control of anticoagulation of the scientific and standardisation committee of the international society on thrombosis and haemostasis. J Thromb Haemost [Epub ahead of print]
26. Harenberg J, Marx S, Weiss C, Krämer R, Samama M, Schulman S (2012) Subcommittee on control of anticoagulation of the ISTH. Report of the subcommittee of control of anticoagulation on the determination of the anticoagulant effects of rivaroxaban. J Thromb Haemost 10:1433–1436
27. Douxfils J, Chatelain C, Chatelain B, Dogné JM, Mullier F (2013) Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide. Thromb Haemost 110:283–294
28. Majeed A, Hwang HG, Connolly SJ et al (2013) Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation; epub ahead of print
29. Piccini JP, Garg J, Patel MR et al. Management of major bleedings events in patients treated with rivaroxaban vs warfarin: results from ROCKET AF trial. Eur Heart J; epub ahead of print
30. van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A (2010) Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 103:1116–1127
31. Lillo-Le Louët A, Wolf M, Soufir L et al (2012) Life-threatening bleeding in four patients with an unusual excessive response to dabigatran: implications for emergency surgery and resuscitation. Thromb Haemost 108:583–585
32. Schulman S, Ritchie B, Goy JK, Nahirniak S, Almutawa M, Ghanny S (2014) Activated prothrombin complex concentrate for dabigatran-associated bleeding. Br J Haematol 164:308–310
33. Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M (2011) Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation 124:1573–1579
34. Hoffman M, Dargaud Y (2012) Mechanisms and monitoring of bypassing agent therapy. J Thromb Haemost 10:1478–1485
35. Herrmann R, Thom J, Wood A, Phillips M, Muhammad S, Baker R (2013) Thrombin generation using the calibrated automated thrombinoscope to assess reversibility of dabigatran and rivaroxaban. Thromb Haemost 111(5). Epub ahead of print
36. Escolar G, Fernandez-Gallego V, Arellano-Rodrigo E et al (2013) Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood. PLoS ONE 8:e78696
37. Schiele F, van Ryn J, Canada K, Newsome C, Sepulveda E, Park J, Nar H, Litzenburger T (2013) A specific antidote for dabigatran: functional and structural characterization. Blood 121:3554–3562
38. Lu G, Deguzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, Luan P, Hutchaleelaha A, Inagaki M, Conley PB, Phillips DR, Sinha U (2013) A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med 19:446–451
39. Grottke O, van Ryn J, Spronk HM, Rossaint R (2014) Prothrombin complex concentrates and a specific antidote to dabigatran are effective ex vivo in reversing the effects of dabigatran in an anticoagulation/liver trauma experimental model. Crit Care 18:R27