Login Register Cart 0
Generic placeholder image

Cardiovascular & Hematological Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5257
ISSN (Online): 1875-6182

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Direct (New) Oral Anticoagulants (DOACs): Drawbacks, Bleeding and Reversal

Author(s): Ozgur Karcioglu*, Sehmus Zengin, Bilgen Ozkaya, Eylem Ersan, Sarper Yilmaz, Goksu Afacan, Derya Abuska, Mandana Hosseinzadeh and Selman Yeniocak

Volume 20, Issue 2, 2022

Published on: 14 September, 2021

Page: [103 - 113] Pages: 11

DOI: 10.2174/1871525719666210914110750

Price: $65

Abstract

Background and Objective: Direct (new) Oral Anticoagulants (DOACs) have emerged as a contemporary and promising option in the treatment of thromboses and VTE, while protecting the coagulation cascade against untoward bleeding events. They are used in the management and prophylaxis of Venous Thromboembolism (VTE) and other thrombotic diseases. The most prominent complication of these agents is bleeding. These agents have similar or lower rates of major intracranial hemorrhages, while they had a higher risk of major gastrointestinal bleeding when compared to warfarin. This manuscript is aimed to revise and update the literature findings to outline the side effects of DOACs in various clinical scenarios.

Methods: A narrative review of currently published studies was performed. Online database searches were performed for clinical trials published before July 2021, on the efficacy and adverse effects attributed to the anticoagulant treatment, especially DOACs. A literature search via electronic databases was carried out, beginning with the usage of the agents in the Western Languages papers. The search terms initially included direct (new) oral anticoagulants, dabigatran, rivaroxaban, apixaban, edoxaban, idarucizumab, andexanet, prothrombin complex concentrates, and fresh frozen plasma. Papers were examined for methodological soundness before being included.

Results: Severe bleeding episodes require aggressive interventions for successful management. Therefore, bleeding should be evaluated in special regard to the location and rate of hemorrhage, and total volume of blood loss. Patient's age, weight and organ dysfunctions (e.g., kidney/liver failure or chronic respiratory diseases) directly affect the clinical course of overdose.

Conclusion: Management recommendations for hemorrhage associated with DOAC use vary, depending on the class of the culprit agent (direct thrombin inhibitor vs. FXa inhibitor), the clinical status of the patient (mild/ moderate vs. severe/life-threatening), and capabilities of the institution. Specific reversal agents (i.e., idarucizumab and andexanet alfa) can be used if available, while prothrombin complex concentrates, fresh frozen plasma and/ or tranexamic acid can also be employed as nonspecific replacement agents in the management of DOAC-related bleeding diathesis.

Keywords: Direct oral anticoagulants, bleeding, hemorrhage, dabigatran, rivaroxaban, edoxaban, idarucizumab, andexanet alfa, prothrombin complex concentrate.

Next »
Graphical Abstract

[1]
Mujer, M.T.P.; Rai, M.P.; Atti, V.; Dimaandal, I.L.; Chan, A.S.; Shrotriya, S.; Gundabolu, K.; Dhakal, P. An update on the reversal of non-vitamin k antagonist oral anticoagulants. Adv. Hematol., 2020, 2020, 7636104.
[http://dx.doi.org/10.1155/2020/7636104] [PMID: 32231703]
[2]
López-López, J.A.; Sterne, J.A.C.; Thom, H.H.Z.; Higgins, J.P.T.; Hingorani, A.D.; Okoli, G.N.; Davies, P.A.; Bodalia, P.N.; Bryden, P.A.; Welton, N.J.; Hollingworth, W.; Caldwell, D.M.; Savović, J.; Dias, S.; Salisbury, C.; Eaton, D.; Stephens-Boal, A.; Sofat, R. Oral anticoagulants for prevention of stroke in atrial fibrillation: systematic review, network meta-analysis, and cost effectiveness analysis. BMJ, 2017, 359, j5058.
[http://dx.doi.org/10.1136/bmj.j5058] [PMID: 29183961]
[3]
Held, C.; Hylek, E.M.; Alexander, J.H.; Hanna, M.; Lopes, R.D.; Wojdyla, D.M.; Thomas, L.; Al-Khalidi, H.; Alings, M.; Xavier, D.; Ansell, J.; Goto, S.; Ruzyllo, W.; Rosenqvist, M.; Verheugt, F.W.; Zhu, J.; Granger, C.B.; Wallentin, L. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial. Eur. Heart J., 2015, 36(20), 1264-1272.
[http://dx.doi.org/10.1093/eurheartj/ehu463] [PMID: 25499871]
[4]
Hankey, G.J.; Stevens, S.R.; Piccini, J.P.; Lokhnygina, Y.; Mahaffey, K.W.; Halperin, J.L.; Patel, M.R.; Breithardt, G.; Singer, D.E.; Becker, R.C.; Berkowitz, S.D.; Paolini, J.F.; Nessel, C.C.; Hacke, W.; Fox, K.A.; Califf, R.M. Intracranial hemorrhage among patients with atrial fibrillation anticoagulated with warfarin or rivaroxaban: the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation. Stroke, 2014, 45(5), 1304-1312.
[http://dx.doi.org/10.1161/STROKEAHA.113.004506] [PMID: 24743444]
[5]
Milling, T.J., Jr; Clark, C.L.; Feronti, C.; Song, S.S.; Torbati, S.S.; Fermann, G.J.; Weiss, J.; Patel, D. Management of Factor Xa inhibitor-associated life-threatening major hemorrhage: A retrospective multi-center analysis. Am. J. Emerg. Med., 2018, 36(3), 396-402.
[http://dx.doi.org/10.1016/j.ajem.2017.08.042] [PMID: 28843518]
[6]
Piccini, J.P.; Garg, J.; Patel, M.R.; Lokhnygina, Y.; Goodman, S.G.; Becker, R.C.; Berkowitz, S.D.; Breithardt, G.; Hacke, W.; Halperin, J.L.; Hankey, G.J.; Nessel, C.C.; Mahaffey, K.W.; Singer, D.E.; Califf, R.M.; Fox, K.A. Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial. Eur. Heart J., 2014, 35(28), 1873-1880.
[http://dx.doi.org/10.1093/eurheartj/ehu083] [PMID: 24658769]
[7]
Ruff, C.T.; Giugliano, R.P.; Braunwald, E.; Hoffman, E.B.; Deenadayalu, N.; Ezekowitz, M.D.; Camm, A.J.; Weitz, J.I.; Lewis, B.S.; Parkhomenko, A.; Yamashita, T.; Antman, E.M. 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(9921), 955-962.
[http://dx.doi.org/10.1016/S0140-6736(13)62343-0] [PMID: 24315724]
[8]
Seiffge, D.J.; Paciaroni, M.; Wilson, D.; Koga, M.; Macha, K.; Cappellari, M.; Schaedelin, S.; Shakeshaft, C.; Takagi, M.; Tsivgoulis, G.; Bonetti, B.; Kallmünzer, B.; Arihiro, S.; Alberti, A.; Polymeris, A.A.; Ambler, G.; Yoshimura, S.; Venti, M.; Bonati, L.H.; Muir, K.W.; Yamagami, H.; Thilemann, S.; Altavilla, R.; Peters, N.; Inoue, M.; Bobinger, T.; Agnelli, G.; Brown, M.M.; Sato, S.; Acciarresi, M.; Jager, H.R.; Bovi, P.; Schwab, S.; Lyrer, P.; Caso, V.; Toyoda, K.; Werring, D.J.; Engelter, S.T.; De Marchis, G.M. Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation. Ann. Neurol., 2019, 85(6), 823-834.
[http://dx.doi.org/10.1002/ana.25489] [PMID: 30980560]
[9]
Wolfe, Z.; Khan, S.U.; Nasir, F.; Raghu Subramanian, C.; Lash, B. A systematic review and Bayesian network meta-analysis of risk of intracranial hemorrhage with direct oral anticoagulants. J. Thromb. Haemost., 2018, 16(7), 1296-1306.
[http://dx.doi.org/10.1111/jth.14131] [PMID: 29723935]
[10]
Gerner, S.T.; Kuramatsu, J.B.; Sembill, J.A.; Sprügel, M.I.; Endres, M.; Haeusler, K.G.; Vajkoczy, P.; Ringleb, P.A.; Purrucker, J.; Rizos, T.; Erbguth, F.; Schellinger, P.D.; Fink, G.R.; Stetefeld, H.; Schneider, H.; Neugebauer, H.; Röther, J.; Claßen, J.; Michalski, D.; Dörfler, A.; Schwab, S.; Huttner, H.B. Association of prothrombin complex concentrate administration and hematoma enlargement in non-vitamin K antagonist oral anticoagulant-related intracerebral hemorrhage. Ann. Neurol., 2018, 83(1), 186-196.
[http://dx.doi.org/10.1002/ana.25134] [PMID: 29314216]
[11]
Giugliano, R.P.; Ruff, C.T.; Braunwald, E.; Murphy, S.A.; Wiviott, S.D.; Halperin, J.L.; Waldo, A.L.; Ezekowitz, M.D.; Weitz, J.I.; Špinar, J.; Ruzyllo, W.; Ruda, M.; Koretsune, Y.; Betcher, J.; Shi, M.; Grip, L.T.; Patel, S.P.; Patel, I.; Hanyok, J.J.; Mercuri, M.; Antman, E.M. Edoxaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med., 2013, 369(22), 2093-2104.
[http://dx.doi.org/10.1056/NEJMoa1310907] [PMID: 24251359]
[12]
Beyer-Westendorf, J.; Gelbricht, V.; Förster, K.; Ebertz, F.; Köhler, C.; Werth, S.; Kuhlisch, E.; Stange, T.; Thieme, C.; Daschkow, K.; Weiss, N. Peri-interventional management of novel oral anticoagulants in daily care: results from the prospective Dresden NOAC registry. Eur. Heart J., 2014, 35(28), 1888-1896.
[http://dx.doi.org/10.1093/eurheartj/eht557] [PMID: 24394381]
[13]
Radadiya, D.; Devani, K.; Brahmbhatt, B.; Reddy, C. Major gastrointestinal bleeding risk with direct oral anticoagulants: Does type and dose matter? - A systematic review and network meta-analysis. Eur. J. Gastroenterol. Hepatol., 2021. [Online ahead of print].
[http://dx.doi.org/10.1097/MEG.0000000000002035] [PMID: 33470705]
[14]
Connolly, S.J.; Crowther, M.; Eikelboom, J.W.; Gibson, C.M.; Curnutte, J.T.; Lawrence, J.H.; Yue, P.; Bronson, M.D.; Lu, G.; Conley, P.B.; Verhamme, P.; Schmidt, J.; Middeldorp, S.; Cohen, A.T.; Beyer-Westendorf, J.; Albaladejo, P.; Lopez-Sendon, J.; Demchuk, A.M.; Pallin, D.J.; Concha, M.; Goodman, S.; Leeds, J.; Souza, S.; Siegal, D.M.; Zotova, E.; Meeks, B.; Ahmad, S.; Nakamya, J.; Milling, T.J.Jr., Jr Full study report of andexanet alfa for bleeding associated with factor xa inhibitors. N. Engl. J. Med., 2019, 380(14), 1326-1335.
[http://dx.doi.org/10.1056/NEJMoa1814051] [PMID: 30730782]
[15]
Pollack, C.V., Jr; Reilly, P.A.; van Ryn, J.; Eikelboom, J.W.; Glund, S.; Bernstein, R.A.; Dubiel, R.; Huisman, M.V.; Hylek, E.M.; Kam, C.W.; Kamphuisen, P.W.; Kreuzer, J.; Levy, J.H.; Royle, G.; Sellke, F.W.; Stangier, J.; Steiner, T.; Verhamme, P.; Wang, B.; Young, L.; Weitz, J.I. Idarucizumab for dabigatran reversal - full cohort analysis. N. Engl. J. Med., 2017, 377(5), 431-441.
[http://dx.doi.org/10.1056/NEJMoa1707278] [PMID: 28693366]
[16]
Douxfils, J.; Gosselin, R.C. Laboratory assessment of direct oral anticoagulants. Semin. Thromb. Hemost., 2017, 43(3), 277-290.
[http://dx.doi.org/10.1055/s-0036-1597296] [PMID: 28249326]
[17]
Steiner, T.; Böhm, M.; Dichgans, M.; Diener, H.C.; Ell, C.; Endres, M.; Epple, C.; Grond, M.; Laufs, U.; Nickenig, G.; Riess, H.; Röther, J.; Schellinger, P.D.; Spannagl, M.; Veltkamp, R. Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. Clin. Res. Cardiol., 2013, 102(6), 399-412.
[http://dx.doi.org/10.1007/s00392-013-0560-7] [PMID: 23669868]
[18]
Cuker, A.; Burnett, A.; Triller, D.; Crowther, M.; Ansell, J.; Van Cott, E.M.; Wirth, D.; Kaatz, S. Reversal of direct oral anticoagulants: guidance from the anticoagulation forum. Am. J. Hematol., 2019, 94(6), 697-709.
[http://dx.doi.org/10.1002/ajh.25475] [PMID: 30916798]
[19]
Holbrook, A.; Schulman, S.; Witt, D.M. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis American College of Chest Physicians Evidence-Based Clinical Practice Guidelines, 9th ed; Chest, 2012, 141, pp. (2 Suppl) e152S-e184S.
[20]
Ansell, J.; Hirsh, J.; Hylek, E.; Jacobson, A.; Crowther, M.; Palareti, G. Pharmacology and management of the vitamin k antagonists: american college of chest physicians evidence-based clinical practice guidelines 8th ed. Chest, 2008, 133(6)(Suppl.), 160S-198S.
[http://dx.doi.org/10.1378/chest.08-0670] [PMID: 18574265]
[21]
Kaide, C.G.; Gulseth, M.P. Current strategies for the management of bleeding associated with direct oral anticoagulants and a review of investigational reversal agents. J. Emerg. Med., 2020, 58(2), 217-233.
[http://dx.doi.org/10.1016/j.jemermed.2019.10.011] [PMID: 31831187]
[22]
Shih, A.W.; Crowther, M.A. Reversal of direct oral anticoagulants: A practical approach. Hematology (Am. Soc. Hematol. Educ. Program), 2016, 2016(1), 612-619.
[http://dx.doi.org/10.1182/asheducation-2016.1.612] [PMID: 27913536]
[23]
Stansfield, R.; Morris, D.; Jesulola, E. The use of tranexamic acid (txa) for the management of hemorrhage in trauma patients in the prehospital environment: literature review and descriptive analysis of principal themes. Shock, 2020, 53(3), 277-283.
[http://dx.doi.org/10.1097/SHK.0000000000001389] [PMID: 32044848]
[24]
Smith, S.R.; Murray, D.; Pockney, P.G.; Bendinelli, C.; Draganic, B.D.; Carroll, R. Tranexamic acid for lower gi hemorrhage: a randomized placebo-controlled clinical trial. Dis. Colon Rectum, 2018, 61(1), 99-106.
[http://dx.doi.org/10.1097/DCR.0000000000000943] [PMID: 29215478]
[25]
Ruff, C.T. Reversal agents: what we have and what we can expect. J. Innov. Card. Rhythm Manag., 2018, 9(4), 3108-3114.
[http://dx.doi.org/10.19102/icrm.2018.090403] [PMID: 32477806]
[26]
Eikelboom, J.W.; Quinlan, D.J.; van Ryn, J.; Weitz, J.I. Idarucizumab: the antidote for reversal of dabigatran. Circulation, 2015, 132(25), 2412-2422.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.115.019628] [PMID: 26700008]
[27]
January, C.T.; Wann, L.S.; Calkins, H.; Chen, L.Y.; Cigarroa, J.E.; Cleveland, J.C., Jr; Ellinor, P.T.; Ezekowitz, M.D.; Field, M.E.; Furie, K.L.; Heidenreich, P.A.; Murray, K.T.; Shea, J.B.; Tracy, C.M.; Yancy, C.W. 2019 AHA/ACC/HRS focused update of the 2014 aha/acc/hrs guideline for the management of patients with atrial fibrillation: a report of the american college of cardiology/american heart association task force on clinical practice guidelines and the heart rhythm society in collaboration with the society of thoracic surgeons. Circulation, 2019, 140(2), e125-e151.
[http://dx.doi.org/10.1161/CIR.0000000000000665] [PMID: 30686041]
[28]
Siegal, D.M.; Curnutte, J.T.; Connolly, S.J.; Lu, G.; Conley, P.B.; Wiens, B.L.; Mathur, V.S.; Castillo, J.; Bronson, M.D.; Leeds, J.M.; Mar, F.A.; Gold, A.; Crowther, M.A. Andexanet alfa for the reversal of factor xa inhibitor activity. N. Engl. J. Med., 2015, 373(25), 2413-2424.
[http://dx.doi.org/10.1056/NEJMoa1510991] [PMID: 26559317]
[29]
Panahi, L.; Udeani, G.; Horseman, M.; Weston, J.; Samuel, N.; Joseph, M.; Mora, A.; Bazan, D. Review of medical therapies for the management of pulmonary embolism. Medicina (Kaunas), 2021, 57(2), 110.
[http://dx.doi.org/10.3390/medicina57020110] [PMID: 33530544]
[30]
Ansell, J.E.; Bakhru, S.H.; Laulicht, B.E.; Steiner, S.S.; Grosso, M.A.; Brown, K.; Dishy, V.; Lanz, H.J.; Mercuri, M.F.; Noveck, R.J.; Costin, J.C. Single-dose ciraparantag safely and completely reverses anticoagulant effects of edoxaban. Thromb. Haemost., 2017, 117(2), 238-245.
[http://dx.doi.org/10.1160/TH16-03-0224] [PMID: 27853809]
[31]
Levy, J.H.; Douketis, J.; Weitz, J.I. Reversal agents for non-vitamin K antagonist oral anticoagulants. Nat. Rev. Cardiol., 2018, 15(5), 273-281.
[http://dx.doi.org/10.1038/nrcardio.2017.223] [PMID: 29345686]
[32]
Schulman, S.; Gross, P.L.; Ritchie, B.; Nahirniak, S.; Lin, Y.; Lieberman, L.; Carrier, M.; Crowther, M.A.; Ghosh, I.; Lazo-Langner, A.; Zondag, M. Prothrombin complex concentrate for major bleeding on factor xa inhibitors: a prospective cohort study. Thromb. Haemost., 2018, 118(5), 842-851.
[http://dx.doi.org/10.1055/s-0038-1636541] [PMID: 29564837]
[33]
Kustos, S.A.; Fasinu, P.S. Direct-acting oral anticoagulants and their reversal agents-an update. Medicines (Basel), 2019, 6(4), 103.
[http://dx.doi.org/10.3390/medicines6040103] [PMID: 31618893]
[34]
Burnett, A.E.; Mahan, C.E.; Vazquez, S.R.; Oertel, L.B.; Garcia, D.A.; Ansell, J. Guidance for the practical management of the direct oral anticoagulants (DOACs) in VTE treatment. J. Thromb. Thrombolysis, 2016, 41(1), 206-232.
[http://dx.doi.org/10.1007/s11239-015-1310-7] [PMID: 26780747]
[35]
Heidbuchel, H.; Verhamme, P.; Alings, M.; Antz, M.; Diener, H.C.; Hacke, W.; Oldgren, J.; Sinnaeve, P.; Camm, A.J.; Kirchhof, P. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace, 2015, 17(10), 1467-1507.
[http://dx.doi.org/10.1093/europace/euv309] [PMID: 26324838]
[36]
Ageno, W.; Büller, H.R.; Falanga, A.; Hacke, W.; Hendriks, J.; Lobban, T.; Merino, J.; Milojevic, I.S.; Moya, F.; van der Worp, H.B.; Randall, G.; Tsioufis, K.; Verhamme, P.; Camm, A.J. Managing reversal of direct oral anticoagulants in emergency situations. Thromb. Haemost., 2016, 116(6), 1003-1010.
[PMID: 27488232]
[37]
Ruff, C.T.; Giugliano, R.P.; Antman, E.M. Management of bleeding with non-vitamin K antagonist oral anticoagulants in the era of specific reversal agents. Circulation, 2016, 134(3), 248-261.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.116.021831] [PMID: 27436881]
[38]
Tomaselli, G.F.; Mahaffey, K.W.; Cuker, A.; Dobesh, P.P.; Doherty, J.U.; Eikelboom, J.W.; Florido, R.; Gluckman, T.J.; Hucker, W.J.; Mehran, R.; Messé, S.R.; Perino, A.C.; Rodriguez, F.; Sarode, R.; Siegal, D.M.; Wiggins, B.S. 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the american college of cardiology solution set oversight committee. J. Am. Coll. Cardiol., 2020, 76(5), 594-622.
[http://dx.doi.org/10.1016/j.jacc.2020.04.053] [PMID: 32680646]
[39]
UW Medicine Guidelines for Reversal of Anticoagulants. 2020. Available from: https://depts.washington.edu/anticoag/home/sites/default/files/GUIDELINES%20FOR%20REVERSAL%20OF%20ANTICOAGULANTS.pdf [(accessed on 19 October 2020)].
[40]
Zahir, H.; Brown, K.S.; Vandell, A.G.; Desai, M.; Maa, J.F.; Dishy, V.; Lomeli, B.; Feussner, A.; Feng, W.; He, L.; Grosso, M.A.; Lanz, H.J.; Antman, E.M. Edoxaban effects on bleeding following punch biopsy and reversal by a 4-factor prothrombin complex concentrate. Circulation, 2015, 131(1), 82-90.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.114.013445] [PMID: 25403645]
[41]
Levy, J.H.; Moore, K.T.; Neal, M.D.; Schneider, D.; Marcsisin, V.S.; Ariyawansa, J.; Weitz, J.I. Rivaroxaban reversal with prothrombin complex concentrate or tranexamic acid in healthy volunteers. J. Thromb. Haemost., 2018, 16(1), 54-64.
[http://dx.doi.org/10.1111/jth.13894] [PMID: 29106076]
[42]
Nagalla, S.; Thomson, L.; Oppong, Y.; Bachman, B.; Chervoneva, I.; Kraft, W.K. Reversibility of apixaban anticoagulation with a four-factor prothrombin complex concentrate in healthy volunteers. Clin. Transl. Sci., 2016, 9(3), 176-180.
[http://dx.doi.org/10.1111/cts.12398] [PMID: 27170068]
[43]
Barco, S.; Whitney Cheung, Y.; Coppens, M.; Hutten, B.A.; Meijers, J.C.; Middeldorp, S. In vivo reversal of the anticoagulant effect of rivaroxaban with four-factor prothrombin complex concentrate. Br. J. Haematol., 2016, 172(2), 255-261.
[http://dx.doi.org/10.1111/bjh.13821] [PMID: 26488126]
[44]
Gianni, C.; DI Biase, L.; Mohanty, S.; Trivedi, C.; Bai, R.; Al-Ahmad, A.; Burkhardt, J.D.; Gallinghouse, G.J.; Horton, R.P.; Sanchez, J.E.; Hranitzky, P.M.; Lakkireddy, D.; Mansour, M.C.; Santangeli, P.; Zado, E.S.; Marchlinski, F.E.; Beheiry, S.; Hao, S.C.; Couts, L.; Gibson, D.; Natale, A. Management of periprocedural and early pericardial effusions with tamponade following ablation of atrial fibrillation with uninterrupted factor Xa inhibitors: A case series. J. Cardiovasc. Electrophysiol., 2016, 27(4), 399-403.
[http://dx.doi.org/10.1111/jce.12918] [PMID: 26756289]
[45]
Shaw, J.R.; Siegal, D.M. Pharmacological reversal of the direct oral anticoagulants-A comprehensive review of the literature. Res. Pract. Thromb. Haemost., 2018, 2(2), 251-265.
[http://dx.doi.org/10.1002/rth2.12089] [PMID: 30046727]
[46]
Brekelmans, M.P.A.; Ginkel, K.V.; Daams, J.G.; Hutten, B.A.; Middeldorp, S.; Coppens, M. Benefits and harms of 4-factor prothrombin complex concentrate for reversal of vitamin K antagonist associated bleeding: A systematic review and meta-analysis. J. Thromb. Thrombolysis, 2017, 44(1), 118-129.
[http://dx.doi.org/10.1007/s11239-017-1506-0] [PMID: 28540468]
[47]
Chai-Adisaksopha, C.; Hillis, C.; Siegal, D.M.; Movilla, R.; Heddle, N.; Iorio, A.; Crowther, M. Prothrombin complex concentrates versus fresh frozen plasma for warfarin reversal. A systematic review and meta-analysis. Thromb. Haemost., 2016, 116(5), 879-890.
[http://dx.doi.org/10.1160/TH16-04-0266] [PMID: 27488143]
[48]
Sadeghi, N.; Kahn, D.; Cunanan, J. Compositional differences in commercially available prothrombin complex concentrates. Blood, 2012, 120(21), 4391.
[http://dx.doi.org/10.1182/blood.V120.21.4391.4391]
[49]
Voils, S.A.; Baird, B. Systematic review: 3-factor versus 4-factor prothrombin complex concentrate for warfarin reversal: does it matter? Thromb. Res., 2012, 130(6), 833-840.
[http://dx.doi.org/10.1016/j.thromres.2012.10.001] [PMID: 23137921]
[50]
Mega, J.L.; Braunwald, E.; Wiviott, S.D.; Bassand, J.P.; Bhatt, D.L.; Bode, C.; Burton, P.; Cohen, M.; Cook-Bruns, N.; Fox, K.A.; Goto, S.; Murphy, S.A.; Plotnikov, A.N.; Schneider, D.; Sun, X.; Verheugt, F.W.; Gibson, C.M. Rivaroxaban in patients with a recent acute coronary syndrome. N. Engl. J. Med., 2012, 366(1), 9-19.
[http://dx.doi.org/10.1056/NEJMoa1112277] [PMID: 22077192]
[51]
Wang, Q.; Yang, K. Dual therapy with an oral non-vitamin K antagonist and a P2Y12 inhibitor vs triple therapy with aspirin, a P2Y12 inhibitor and a vitamin K antagonist for the treatment of diabetes mellitus patients with co-existing atrial fibrillation following percutaneous coronary intervention: A meta-analysis. Medicine (Baltimore), 2021, 100(15), e25546.
[http://dx.doi.org/10.1097/MD.0000000000025546] [PMID: 33847681]
[52]
Hinojar, R.; Jiménez-Natcher, J.J.; Fernández-Golfín, C.; Zamorano, J.L. New oral anticoagulants: A practical guide for physicians. Eur. Heart J. Cardiovasc. Pharmacother., 2015, 1(2), 134-145.
[http://dx.doi.org/10.1093/ehjcvp/pvv002] [PMID: 27533984]

Rights & Permissions Print Cite
Article Metrics
74
1
© 2024 Bentham Science Publishers | Privacy Policy