Thromb Haemost 2013; 110(02): 205-212
DOI: 10.1160/TH13-02-0150
Clinical Focus
Schattauer GmbH

Gastrointestinal bleeding with the new oral anticoagulants – defining the issues and the management strategies

Jay Desai
1   Department of Medicine (Division of Gastroenterology), New York University, New York, New York, USA
,
Jennifer M. Kolb
2   Department of Medicine (Division of Gastroenterology), Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Jeffrey I. Weitz
3   Departments of Medicine and Biochemistry and Biomedical Sciences, McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
,
James Aisenberg
2   Department of Medicine (Division of Gastroenterology), Icahn School of Medicine at Mount Sinai, New York, New York, USA
› Institutsangaben
Financial support: Jay Desai and Jennifer M. Kolb were supported by grants from the Digestive Disease Research Foundation.
Weitere Informationen

Publikationsverlauf

Received: 19. Februar 2013

Accepted after minor revision: 27. April 2013

Publikationsdatum:
04. Dezember 2017 (online)

 

 
  • References

  • 1 Kwong LM. Rivaroxaban, an oral, direct factor Xa inhibitor: a new option for thromboprophylaxis. Orthopedics 2012; 35: e932-938.
  • 2 Lassen MR, Raskob GE, Gallus A. et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010; 375: 807-815.
  • 3 Connolly S, Ezekowitz M B C, Salim Y. et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. New Engl J Med 2009; 361: 1139-1151.
  • 4 Patel M, Mahaffey K, Garg J. et al. Rivaroxaban versus Warfarin in Nonvavular Atrial Fibrillation. New Engl J Med 2011; 365: 883-891.
  • 5 Granger C, Alexander J, McMurray J. et al. Apixaban versus Warfarin in Patients with Atrial Fribrillation. New Engl J Med 2011; 365: 981-992.
  • 6 Ganetsky M, Babu KM, Salhanick SD. et al. Dabigatran: review of pharmacology and management of bleeding complications of this novel oral anticoagulant. J Med Toxicol 2011; 07: 281-287.
  • 7 Raghavan N, Frost CE, Yu Z. et al. Apixaban Metabolism and Pharmacokinetics after Oral Administration to Humans. Drug Metab Dispos 2009; 37: 74-81.
  • 8 Blech S, Ebner T, Ludwig-Schwellinger E. et al. The Metabolism and Disposition of the Oral Direct Thrombin Inhibitor, Dabigatran, in Humans. Drug Metabol Disp 2008; 36: 386-399.
  • 9 Weinz C, Schwarz T, Kubitza D. et al. Metabolism and Excretion of Rivaroxaban, an Oral, Direct Factor Xa Inhibitor, in Rats, Dogs, and Humans. Drug Metab Dispos 2009; 37 (05) 1056-64.
  • 10 Coleman CI, Sobieraj DM, Winkler S. et al. Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation. Int J Clin Pract 2012; 66: 53-63.
  • 11 Rubin T, Murdoch M, Nelson DB. Acute GI bleeding in the setting of supratherapeutic international normalized ratio in patients taking warfarin: endoscopic diagnosis, clinical management, and outcomes. Gastrointest Endoscopy 2003; 58: 369-373.
  • 12 Di Caro S, May A, Heine DGN. et al. The European experience with double-balloon enteroscopy: indications, methodology, safety, and clinical impact. Gastrointest Endoscopy 2005; 62: 545-550.
  • 13 Gay G, Delvaux M, Rey JF. The role of video capsule endoscopy in the diagnosis of digestive diseases: a review of current possibilities. Endoscopy 2004; 36: 913-920.
  • 14 Zuckerman GR, Prakash C, Askin MP. et al. AGA technical review on the evaluation and management of occult and obscure gastrointestinal bleeding. Gastroenterology 2000; 118: 201-221.
  • 15 Schulman S, Angerås U, Bergqvist D. et al. Definition of major bleeding in clinical investigations of antihaemostatic medicinal products in surgical patients. J Thromb Haemost 2010; 08: 202-204.
  • 16 Eikelboom JW, Wallentin L, Connolly SJ. et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011; 123: 2363-2372.
  • 17 Nessel C, Mahaffey K, Piccini JP. et al. Incidence and Outcomes of Gastrointestinal Haemorrhage in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: Results From the ROCKET AF Trial (abstract). Chest 2012; 142: 84A.
  • 18 Southworth MR, Reichman ME, Unger EF. Dabigatran and Postmarketing Reports of Bleeding. New Engl J Med. 2013 Epub ahead of print.
  • 19 European Medicines Agency Human medicines. European Medicines Agency updates patient and prescriber information for Pradaxa [Internet]. Available from: http://www.ema.europa.eu/ema/ index.jsp?curl=pages/medicines/human/public_health_alerts/2012/05/human_pha_detail_000061.jsp&mid=WC0b01ac058001d126
  • 20 Drug Safety and Availability FDA Drug Safety Communication: Update on the risk for serious bleeding events with the anticoagulant Pradaxa (dabigatran) [Internet]. Center for Drug Evaluation and Research. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm
  • 21 Lim YJ, Yang C-H. Non-steroidal anti-inflammatory drug-induced enteropathy. Clin Endoscopy 2012; 45: 138-144.
  • 22 FDA Advisory Committee Briefing Document. Boehringer Ingelheim. Dabigatran etexilate 2010; 1-168.
  • 23 Dans AL, Connolly SJ, Wallentin L. et al. Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Trial. Circulation 2013; 127: 634-640.
  • 24 Goldstein JL, Eisen GM, Lewis B. et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Therapeut 2007; 25: 1211-1222.
  • 25 Laine L, Maller ES, Yu C. et al. Ulcer formation with low-dose enteric-coated aspirin and the effect of COX-2 selective inhibition: a double-blind trial. Gastroenterology 2004; 127: 395-402.
  • 26 Kernan L, Ito S, Shirazi F. et al. Fatal gastrointestinal haemorrhage after a single dose of dabigatran. Clin Toxicol 2012; 50: 571-573.
  • 27 Fellows SE, Rosini JM, Curtis JA. et al. Haemorrhagic Gastritis with Dabigatran in a Patient with Renal Insufficiency. J Emerg Med 2012; 44: e221-e225.
  • 28 Wychowski MK, Kouides P a. Dabigatran-induced gastrointestinal bleeding in an elderly patient with moderate renal impairment. Ann Pharmacotherapy 2012; 46: e10.
  • 29 Pisters R, Lane D, Nieuwlaat R. et al. A novel userfriendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest 2010; 138: 1093-1100.
  • 30 Garcia D, Barrett YC, Ramacciotti E. et al. Laboratory assessment of the anticoagulant effects of the next generation of oral anticoagulants. J Thromb Haemost 2013; 11: 245-252.
  • 31 Frost C, Wang J, Nepal S. et al. Apixaban, an oral, direct factor Xa inhibitor: single-dose safety, pharmacokinetics, pharmacodynamics and food effect in healthy subjects. Br J Clin Pharmacol 2013; 75: 476-487.
  • 32 Van Ryn J, Stangier J, Haertter S. et al. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116-1127.
  • 33 Davila RE, Rajan E, Adler DG. et al. ASGE Guideline: the role of endoscopy in the patient with lower-GI bleeding. Gastrointest Endoscopy 2005; 62: 656-660.
  • 34 Dunn CJ, Goa KL. Fibrin sealant: a review of its use in surgery and endoscopy. Drugs 1999; 58: 863-886.
  • 35 Leung E-LKi, Lau JYW. New endoscopic haemostasis methods. Clin Endoscopy 2012; 45: 224-229.
  • 36 Pragst I, Zeitler SH, Doerr B. et al. Reversal of dabigatran anticoagulation by prothrombin complex concentrate (Beriplex P/N) in a rabbit model. J Thromb Haemost 2012; 10: 1841-1848.
  • 37 Dumkow LE, Voss JR, Peters M. et al. Reversal of dabigatran-induced bleeding with a prothrombin complex concentrate and fresh frozen plasma. J Am Soc Health System Pharmacists 2012; 69: 1646-1650.
  • 38 Godier A, Miclot A, Le BBonniec. et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology 2012; 116: 94-102.
  • 39 Stangier J, Rathgen K, Stähle H. et al. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, singlecentre study. Clin Pharmacokinet 2010; 49: 259-268.
  • 40 Van Ryn J, Litzenburger T, Schurer J. Reversal of Anticoagulant Activity of Dabigatran and Dabigatran-induced Bleeding in Rats by a Specific Antidote (Antibody Fragment) (abstract). Circulation. 2012 Available from: http://circ.ahajournals.org/cgi/content/meeting_abstract/126/21_MeetingAbstracts/A9928
  • 41 Kwok A, Faigel DO. Management of anticoagulation before and after gastrointestinal endoscopy. Am J Gastroenterol 2009; 104: 3085-3097 quiz 3098.
  • 42 Weitz JI, Quinlan DJ, Eikelboom JW. Periprocedural Management and Approach to Bleeding in Patients Taking Dabigatran. Circulation 2012; 126: 2428-2432.
  • 43 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: 343-348.