American Journal of Clinical and Experimental Medicine

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Bleeding Complications in Patients Receiving Direct Oral Anticoagulant Therapy in the Post Clinical Trial General Practice

Received: 31 January 2017    Accepted: 14 February 2017    Published: 10 April 2017
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Abstract

Dabigatran, apixaban and rivaroxaban are direct oral anticoagulants (DOACs) recently approved for patients with venous thromboembolism. Therapy-induced hemorrhage remains a major complication in these patients. This study retrospectively reviews the hemorrhagic complications associated with DOACs in the general practice and the related clinical implications. The electronic medical charts of 2255 patients with prolonged PTT tests during August 2015 to April 2016 at William Beaumont Health System – Troy were retrospectively reviewed. Patients with prolonged PTT and simultaneously receiving DOAC’s were identified. Hemorrhagic complications associated with DOAC therapy and the related clinical information were analyzed. 517 (22.9%) patients were identified receiving DOAC therapy. Among these, DOAC therapy-associated hemorrhages were recorded in 85 patients (16.4%). Apixaban had a significantly lower incidence of hemorrhage (8.8%) than rivaroxaban (21.0%) and dabigatran (27.9%). The most common hemorrhage was GI bleeding (7.0% overall); its incidence was significantly higher in dabigatran (18.6%) than apixaban (4.1%) and rivaroxaban (7.4%); but no significant difference between apixaban and rivaroxaban (p>0.05). GI bleeding produced anemia in 13 patients who received additional treatments with occasional blood transfusions. Since GI bleeding is the most common bleeding complication and may cause anemia in patients receiving DOAC therapy, routine studies for GI bleeding should be encouraged to reduce the complications of GI bleeding. Apixaban has significantly lower incidence of bleeding complications, it may be a better choice in patients with increased bleeding risk overall. However, apixaban may not improve the bleeding risk in patients with GI bleeding associated with rivaroxaban.

DOI 10.11648/j.ajcem.20170503.12
Published in American Journal of Clinical and Experimental Medicine (Volume 5, Issue 3, May 2017)
Page(s) 64-68
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Anticoagulants, Gastrointestinal Hemorrhage, Activated Partial Thromboplastin Time, Apixaban, Rivaroxaban, Dabigatran

References
[1] Bacchus F and Schulman S. Clinical experience with the new oral anticoagulants for treatment of venous thromboembolism. Arterioscler Thromb Vasc Biol. March 2015, P1-7.
[2] Yao X, Abraham NS, Sangaralingham LR, Bellolio MF, McBane RD, Shah ND and Noseworthy PA. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc. 2016;.116.003725.
[3] Mantha S and Ansell J. Indirect comparison of dabigatran, rivaroxaban, apixaban and edoxaban for the treatment of acute venous thromboembolism. J Thromb Thrombolysis. 2015; 39 (2): 155-65.
[4] Riva N and Ageno W. Pros and cons of vitamin K antagonists and non–vitamin K antagonist oral anticoagulants. Semin Thromb Hemost 2015; 41 (2): 178-187.
[5] Ebright J and Mousa SA. Oral anticoagulants and status of antidotes for the reversal of bleeding risk. Clinical and Applied Thrombosis/Hemostasis 2015; 21 (2): 105-114.
[6] Gehrie E and Tormey C. Novel oral anticoagulants: efficacy, laboratory measurement, and approaches to emergent reversal. Arch Pathol Lab Med 2015; 139 (5): 687-692.
[7] Pollack CV. Introduction to direct oral anticoagulants and rationale for specific reversal agents. Am J Med. 2016; 129: S31-S32.
[8] Ufer M. Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban, and apixaban in preclinical and clinical development. Thromb Haemost 2010; 103 (3): 572.
[9] 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 randomized trials. Lancet 2014; 383: 955-62.
[10] Alotaibi G, Alsaleh K, Wu C, and Mcmurty MS. Dabigatran, rivaroxaban and apixaban for the extended venous thromboembolism treatment: network meta-analysis. Int Angiol, 2014; 33 (4): 301-8.
[11] Abraham NS, Singh S, Alexander GC, Heien H, Haas LR, Crown W and Shah ND. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 2015; 350: h1857.
[12] Tran H, Joseph J, Young L, McRae S, Curnow J, Nandurkar H, Wood P, McLintock C. New oral anticoagulants: a practical guide on prescription, laboratory testing and peri-procedural/bleeding management. Australasian Society of Thrombosis and Haemostasis. Intern Med J. 2014; 44 (6): 525-36.
[13] Franchini M, Bonfanti C and Mannucci PM. Management of bleeding associated with new oral anticoagulants. Semin Thromb Hemost 2015; 41 (7): 788–801.
[14] Villines TC and Peacock WF. Safety of direct oral anticoagulants: Insights from postmarketing studies. Am J Med. 2016; 129: S41-S46.
[15] Eikelboom J and Merli G. Bleeding with direct oral anticoagulants vs warfarin: Clinical experience. Am J Med. 2016; 129: S33-S40.
[16] Favaloro EJ, Lippi G, Koutts J. Laboratory testing of anticoagulants: the present and the future. Pathology 2011; 43 (7): 682–692.
[17] Mary Wyrzykowski, Victoria Walley-Goike and Ming Xie. Retrospective analysis of abnormal partial thromboplastin time results in patients receiving new oral anticoagulants. Am J Clin Pathol 2016; 146 (suppl 1): 106 (abstract).
[18] Halperin JL, Hankey GJ, Wojdyla DM, et al. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 2014; 130: 138-46.
[19] McMahon BJ and Kwaan HC. The new or non–vitamin K antagonist oral anticoagulants: what have we learned since their debut. Semin Thromb Hemost 2015; 41 (2): 188–194.
[20] Forman DE and Goyette RE. Oral anticoagulation therapy for elderly patients with atrial fibrillation: utility of bleeding risk covariates to better understand and moderate risks. Clinical and Applied Thrombosis/Hemostasis 2014; 20 (1): 5-15.
[21] Holster IL, Valkhoff VE, Kuipers EJ, et al. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 2013; 145: 105-12.
[22] Villines TC, Schnee J, Fraeman K, et al. The comparative safety and effectiveness of the oral anticoagulant (OAC) dabigatran versus warfarin utilized in a large healthcare system in non-valvular atrial fibrillation (NVAF) patients. Circulation. 2014; 130 (suppl 2): A18353.
[23] Tepper P, Mardekian J, Masseria C, et al. Real-world comparison of bleeding risks among non-valvular atrial fibrillation patients on apixaban, dabigatran, rivaroxaban: cohorts comprising new initiators and/or switchers from warfarin. Eur Heart J. 2015; 36 (suppl): 339.
Author Information
  • Department of Pathology, Oakland University School of Medicine, William Beaumont Hospital, Troy, Michigan, USA

  • Department of Pathology, Oakland University School of Medicine, William Beaumont Hospital, Troy, Michigan, USA

  • Department of Pathology, Oakland University School of Medicine, William Beaumont Hospital, Troy, Michigan, USA

  • Department of Pathology, Oakland University School of Medicine, William Beaumont Hospital, Troy, Michigan, USA

  • Department of Pathology, Oakland University School of Medicine, William Beaumont Hospital, Troy, Michigan, USA

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  • APA Style

    Subhash Edupuganti, Catherine Xie, Mary Wyrzykowski, Elizabeth Wey, Ming Xie. (2017). Bleeding Complications in Patients Receiving Direct Oral Anticoagulant Therapy in the Post Clinical Trial General Practice. American Journal of Clinical and Experimental Medicine, 5(3), 64-68. https://doi.org/10.11648/j.ajcem.20170503.12

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    ACS Style

    Subhash Edupuganti; Catherine Xie; Mary Wyrzykowski; Elizabeth Wey; Ming Xie. Bleeding Complications in Patients Receiving Direct Oral Anticoagulant Therapy in the Post Clinical Trial General Practice. Am. J. Clin. Exp. Med. 2017, 5(3), 64-68. doi: 10.11648/j.ajcem.20170503.12

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    AMA Style

    Subhash Edupuganti, Catherine Xie, Mary Wyrzykowski, Elizabeth Wey, Ming Xie. Bleeding Complications in Patients Receiving Direct Oral Anticoagulant Therapy in the Post Clinical Trial General Practice. Am J Clin Exp Med. 2017;5(3):64-68. doi: 10.11648/j.ajcem.20170503.12

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  • @article{10.11648/j.ajcem.20170503.12,
      author = {Subhash Edupuganti and Catherine Xie and Mary Wyrzykowski and Elizabeth Wey and Ming Xie},
      title = {Bleeding Complications in Patients Receiving Direct Oral Anticoagulant Therapy in the Post Clinical Trial General Practice},
      journal = {American Journal of Clinical and Experimental Medicine},
      volume = {5},
      number = {3},
      pages = {64-68},
      doi = {10.11648/j.ajcem.20170503.12},
      url = {https://doi.org/10.11648/j.ajcem.20170503.12},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ajcem.20170503.12},
      abstract = {Dabigatran, apixaban and rivaroxaban are direct oral anticoagulants (DOACs) recently approved for patients with venous thromboembolism. Therapy-induced hemorrhage remains a major complication in these patients. This study retrospectively reviews the hemorrhagic complications associated with DOACs in the general practice and the related clinical implications. The electronic medical charts of 2255 patients with prolonged PTT tests during August 2015 to April 2016 at William Beaumont Health System – Troy were retrospectively reviewed. Patients with prolonged PTT and simultaneously receiving DOAC’s were identified. Hemorrhagic complications associated with DOAC therapy and the related clinical information were analyzed. 517 (22.9%) patients were identified receiving DOAC therapy. Among these, DOAC therapy-associated hemorrhages were recorded in 85 patients (16.4%). Apixaban had a significantly lower incidence of hemorrhage (8.8%) than rivaroxaban (21.0%) and dabigatran (27.9%). The most common hemorrhage was GI bleeding (7.0% overall); its incidence was significantly higher in dabigatran (18.6%) than apixaban (4.1%) and rivaroxaban (7.4%); but no significant difference between apixaban and rivaroxaban (p>0.05). GI bleeding produced anemia in 13 patients who received additional treatments with occasional blood transfusions. Since GI bleeding is the most common bleeding complication and may cause anemia in patients receiving DOAC therapy, routine studies for GI bleeding should be encouraged to reduce the complications of GI bleeding. Apixaban has significantly lower incidence of bleeding complications, it may be a better choice in patients with increased bleeding risk overall. However, apixaban may not improve the bleeding risk in patients with GI bleeding associated with rivaroxaban.},
     year = {2017}
    }
    

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  • TY  - JOUR
    T1  - Bleeding Complications in Patients Receiving Direct Oral Anticoagulant Therapy in the Post Clinical Trial General Practice
    AU  - Subhash Edupuganti
    AU  - Catherine Xie
    AU  - Mary Wyrzykowski
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    JO  - American Journal of Clinical and Experimental Medicine
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    AB  - Dabigatran, apixaban and rivaroxaban are direct oral anticoagulants (DOACs) recently approved for patients with venous thromboembolism. Therapy-induced hemorrhage remains a major complication in these patients. This study retrospectively reviews the hemorrhagic complications associated with DOACs in the general practice and the related clinical implications. The electronic medical charts of 2255 patients with prolonged PTT tests during August 2015 to April 2016 at William Beaumont Health System – Troy were retrospectively reviewed. Patients with prolonged PTT and simultaneously receiving DOAC’s were identified. Hemorrhagic complications associated with DOAC therapy and the related clinical information were analyzed. 517 (22.9%) patients were identified receiving DOAC therapy. Among these, DOAC therapy-associated hemorrhages were recorded in 85 patients (16.4%). Apixaban had a significantly lower incidence of hemorrhage (8.8%) than rivaroxaban (21.0%) and dabigatran (27.9%). The most common hemorrhage was GI bleeding (7.0% overall); its incidence was significantly higher in dabigatran (18.6%) than apixaban (4.1%) and rivaroxaban (7.4%); but no significant difference between apixaban and rivaroxaban (p>0.05). GI bleeding produced anemia in 13 patients who received additional treatments with occasional blood transfusions. Since GI bleeding is the most common bleeding complication and may cause anemia in patients receiving DOAC therapy, routine studies for GI bleeding should be encouraged to reduce the complications of GI bleeding. Apixaban has significantly lower incidence of bleeding complications, it may be a better choice in patients with increased bleeding risk overall. However, apixaban may not improve the bleeding risk in patients with GI bleeding associated with rivaroxaban.
    VL  - 5
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