Antidotes for Novel Oral Anticoagulants: Current Status and Future Potential
Abstract
The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ciraparantag (PER977) is an antidote targeted to reverse both direct thrombin and factor Xa inhibitors as well as the indirect inhibitor enoxaparin.
“Another agent under development is ciraparantag (PER977), an antidote targeted to reverse both direct thrombin and factor Xa inhibitors as well as the indirect inhibitor enoxaparin.509”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [509]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62343-0 · Cited by 5,051 · see citing works
Reversal of Rivaroxaban and Dabigatran by Prothrombin Complex Concentrate
Eerenberg, E. S., Kamphuisen, P. W., Sijpkens, M. K., Meijers, J. C. M., Buller, H. R., & Levi, M. M. (2011) · Circulation · doi:10.1161/circulationaha.111.029017 · Cited by 1,353 · see citing works
Stangier, J., Rathgen, K., Stähle, H., & Mazur, D. (2010) · Clinical Pharmacokinetics · doi:10.2165/11318170-000000000-00000 · Cited by 720 · see citing works
Lu, G., DeGuzman, F. R., Hollenbach, S. J., Karbarz, M. J., Abe, K. Y., Lee, G., Luan, P., Hutchaleelaha, A., Inagaki, M., Conley, P. B., et al. (2013) · Nature Medicine · doi:10.1038/nm.3102 · Cited by 700 · see citing works
Conditioning regimens for hematopoietic cell transplantation: one size does not fit all
Gyurkocza, B., & Sandmaier, B. M. (2014) · Blood · doi:10.1182/blood-2014-02-514778 · Cited by 616 · see citing works
A specific antidote for dabigatran: functional and structural characterization
Schiele, F., van Ryn, J., Canada, K. A., Newsome, C., Sepulveda, E., Park, J., Nar, H., & Litzenburger, T. (2013) · Blood · doi:10.1182/blood-2012-11-468207 · Cited by 561 · see citing works
Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban
Marlu, R., Hodaj, E., Paris, A., Albaladejo, P., Cracowski, J., & Pernod, G. (2012) · Thrombosis and Haemostasis · doi:10.1160/th12-03-0179 · Cited by 539 · see citing works
Use of PER977 to Reverse the Anticoagulant Effect of Edoxaban
Ansell, J., Bakhru, S., Laulicht, B., Steiner, S. S., GROSSO, M. A., Brown, K. S., Dishy, V., Noveck, R. J., & Costin, J. C. (2014) · New England Journal of Medicine · doi:10.1056/nejmc1411800 · Cited by 414 · see citing works
Makris, M., Greaves, M., Phillips, W. S., Kitchen, S., Rosendaal, F. R., & Preston, F. E. (1997) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1655992 · Cited by 397 · see citing works
Pernod, G., Albaladejo, P., Godiér, A., Samama, C. M., Susen, S., Gruel, Y., Blais, N., Fontana, P., Cohen, A. A., Llau, J. V., et al. (2013) · Archives of cardiovascular diseases · doi:10.1016/j.acvd.2013.04.009 · Cited by 306 · see citing works
Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays
Hillarp, A., Baghaei, F., Fagerberg, I., Gustafsson, K. M., Stigendal, L., Sten-Linder, M., Strandberg, K., & Lindahl, T. L. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.04098.x · Cited by 287 · see citing works
Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays
Baghaei, F., Fagerberg, I., Gustafsson, K. M., Stigendal, L., Sten-Linder, M., Strandberg, K., Hillarp, A., Lindahl, T. L., & and from the expert group on coagulation of the External Quality Assurance in Laboratory Medicine in Sweden (2010) · Thrombosis and Haemostasis · doi:10.1160/th10-06-0342 · Cited by 268 · see citing works
Zahir, H., Brown, K. S., Vandell, A. G., Desai, M., Maa, J., Dishy, V., Lomeli, B., Feussner, A., Feng, W., He, L., et al. (2014) · Circulation · doi:10.1161/circulationaha.114.013445 · Cited by 250 · see citing works
Contant, G., Spiro, T. E., Perzborn, E., Guinet, C., Gourmelin, Y., Flem, L. L., Rohde, G., Martinoli, J. L., Samama, M. M., & Laboratories, F. T. R. A.-F. X. C. A. F. T. (2011) · Thrombosis and Haemostasis · doi:10.1160/th11-06-0391 · Cited by 231 · see citing works
Guideline on the management of bleeding in patients on antithrombotic agents
Makris, M., van Veen, J. J., Tait, R. C., Mumford, A. D., & Laffan, M. (2012) · British Journal of Haematology · doi:10.1111/bjh.12107 · Cited by 229 · see citing works
Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide
Chatelain, C., Châtelain, B., Douxfils, J., Dogné, J., & Mullier, F. (2013) · Thrombosis and Haemostasis · doi:10.1160/th12-12-0898 · Cited by 211 · see citing works
Watson, H. G., Baglin, T. P., Laidlaw, S., Makris, M., & Preston, F. E. (2001) · British Journal of Haematology · doi:10.1046/j.1365-2141.2001.03070.x · Cited by 204 · see citing works
Levi, M. M., Moore, K. T., Castillejos, C. F., Kubitza, D., Berkowitz, S. D., Goldhaber, S. Z., Raghoebar, M., Patel, M. R., Weitz, J. I., & Levy, J. H. (2014) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12599 · Cited by 197 · see citing works
Pragst, I., Zeitler, S., Doerr, B., Kaspereit, F., Herzog, E., Dickneite, G., & van Ryn, J. (2012) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2012.04859.x · Cited by 186 · see citing works
Escolar, G., Fernandez‐Gallego, V., Arellano‐Rodrigo, E., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078696 · Cited by 135 · see citing works
Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates
Gruber, A., Tinel, H., Marzec, U. M., Buetehorn, U., Buchmüller, A., Heitmeier, S., Laux, V., & Perzborn, E. (2013) · Thrombosis and Haemostasis · doi:10.1160/th12-12-0907 · Cited by 124 · see citing works
Crowther, M., Manasar.Vandana, M., Kitt, M., Lu, G., Conley, P. B., Hollenbach, S. J., Castillo, J., Hutchaleelaha, A., Karbarz, M. J., Lin, J. P., et al. (2013) · Blood · doi:10.1182/blood.v122.21.3636.3636 · Cited by 115 · see citing works
Self-citationThom, J. Y., Wood, A., Phillips, M. R., Shoaib, M., Baker, R. I., & Herrmann, R. (2013) · Thrombosis and Haemostasis · doi:10.1160/th13-07-0607 · Cited by 101 · see citing works
Use of Recombinant Activated Factor VII in Patients Without Hemophilia
Hsia, C. C., Chin-Yee, I. H., & McAlister, V. C. (2008) · Annals of Surgery · doi:10.1097/sla.0b013e318176c4ec · Cited by 101 · see citing works
Extracorporeal Therapy for Dabigatran Removal in the Treatment of Acute Bleeding
Singh, T., Maw, T. T., Henry, B. L., Pastor‐Soler, N. M., Unruh, M. L., Hallows, K. R., & Nolin, T. D. (2013) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.01570213 · Cited by 101 · see citing works
Perzborn, E., Heitmeier, S., Laux, V., & Buchmüller, A. (2014) · Thrombosis Research · doi:10.1016/j.thromres.2014.01.017 · Cited by 99 · see citing works
Grottke, O., van Ryn, J., Spronk, H. M. H., & Rossaint, R. (2014) · Critical Care · doi:10.1186/cc13717 · Cited by 99 · see citing works
Lambourne, M. D., Eltringham‐Smith, L. J., Gataiance, S., Arnold, D. M., Crowther, M. A., & Sheffield, W. P. (2012) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2012.04863.x · Cited by 97 · see citing works
Self-citationMartin, A., Bonniec, B. L., Fischer, A., Marchand‐Leroux, C., Gaussem, P., Samama, C. M., & Godiér, A. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.07.152 · Cited by 96 · see citing works
Crowther, M. A., Levy, G. G., Lu, G., Leeds, J. M., Lin, J. P., Pratikhya, P., Conley, P. B., Connolly, S. J., & Curnutte, J. T. (2014) · Blood · doi:10.1182/blood.v124.21.4269.4269 · Cited by 93 · see citing works
Self-citationDager, W. E., Gosselin, R. C., & Roberts, A. J. (2013) · Critical Care Medicine · doi:10.1097/ccm.0b013e31827caaa3 · Cited by 90 · see citing works
The use of FEIBA ® in the correction of coagulation abnormalities induced by dabigatran
Khoo, T., Weatherburn, C., Kershaw, G. W., et al. (2012) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12005 · Cited by 76 · see citing works
Dinkelaar, J., Molenaar, P. J., Ninivaggi, M., et al. (2013) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12236 · Cited by 72 · see citing works
Laboratory Measurements of the Oral Direct Factor Xa Inhibitor Edoxaban
MORISHIMA, Y., & Kamisato, C. (2015) · American Journal of Clinical Pathology · doi:10.1309/ajcpq2njd3pxftug · Cited by 71 · see citing works
Glund, S., Stangier, J., Schmohl, M., et al. (2014) · Blood · doi:10.1182/blood.v124.21.344.344 · Cited by 70 · see citing works
Dumkow, L. E., Voss, J. R., Peters, M. N., & Jennings, D. L. (2012) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp120055 · Cited by 68 · see citing works
van Ryn, J., Sieger, P., Kink‐Eiband, M., et al. (2009) · Blood · doi:10.1182/blood.v114.22.1065.1065 · Cited by 65 · see citing works
Rosovsky, R. P. G., & Crowther, M. A. (2008) · Hematology · doi:10.1182/asheducation-2008.1.36 · Cited by 63 · see citing works
Self-citationGlund, S., Stangier, J., Schmohl, M., et al. (2013) · Circulation · Cited by 48 · see citing works
Measurement and Reversal of Prophylactic and Therapeutic Peak Levels of Rivaroxaban
Körber, M. K., Langer, E., Ziemer, S., et al. (2013) · Clinical and Applied Thrombosis/Hemostasis · doi:10.1177/1076029613494468 · Cited by 45 · see citing works
Ex vivo reversal of the anticoagulant effects of edoxaban
Halim, A., Samama, M. M., & Mendell, J. (2014) · Thrombosis Research · doi:10.1016/j.thromres.2014.07.036 · Cited by 43 · see citing works
Abstract 11395: Small Molecule Antidote for Anticoagulants
Laulicht, B., Bakhru, S., Lee, C., et al. (2012) · Circulation · Cited by 42 · see citing works
Three or four factor prothrombin complex concentrate for emergency anticoagulation reversal?
Makris, M., & van Veen, J. J. (2011) · PubMed · doi:10.2450/2011.0111-10 · Cited by 39 · see citing works
Gosselin, R. C., Hawes, E. M., Moll, S., et al. (2014) · American Journal of Clinical Pathology · doi:10.1309/ajcprnumi4pvsj7q · Cited by 35 · see citing works
Bakhru, S., Laulicht, B., Jiang, X., et al. (2013) · Circulation · doi:10.1161/circ.128.suppl_22.a18809 · Cited by 32 · see citing works
Hollenbach, S. J., Lu, G., DeGuzman, F. R., et al. (2014) · Circulation · doi:10.1161/circ.130.suppl_2.14657 · Cited by 26 · see citing works
Lu, G., Kotha, J., Cardenas, J. M., et al. (2014) · Circulation · doi:10.1161/circ.130.suppl_2.18218 · Cited by 23 · see citing works
van Ryn, J., Schmoll, M. E., Pillu, H., et al. (2014) · Circulation · doi:10.1161/circ.130.suppl_2.18403 · Cited by 17 · see citing works
Intravenous Lipid Emulsion Does Not Reverse Dabigatran‐induced Anticoagulation in a Rat Model
Blum, J., Carreiro, S., & Hack, J. B. (2013) · Academic Emergency Medicine · doi:10.1111/acem.12225 · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- van Ryn J, Ruehl D, Priepki H, Hauel N, Wienen W. Reversability of the anticoagulant effect of high doses of the direct thrombin inhibitor dabiga- tran by recombinant facotr VIIa or activated prothrombin complex concen- trate. Haematologica. 2008;93:A0370.
- Laulicht B, Bakhru S, Lee C, Baker C, Jiang X, Mathiowitz E, Costin J, Steiner S. Small Molecule Antidote for Anticoagulants. Circulation. 2012;126:A11395.
Cited by
Sorted by citations
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418 · see citing works
2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403 · see citing works
A rapid pro-hemostatic approach to overcome direct oral anticoagulants
Thalji, N. K., Ivanciu, L., Davidson, R., Gimotty, P. A., Krishnaswamy, S., & Camire, R. M. (2016) · Nature Medicine · doi:10.1038/nm.4149 · Cited by 43 · see citing works
- Authors
- Crowther, M., & Crowther, M. A.
- Affiliations
- From the Department of Haematology, Worcestershire Royal Hospital, Worcester, United Kingdom (M.C.); and Department of Haematology, St. Joseph’s Hospital, McMaster University, Hamilton, Ontario, Canada (M.A.C.).
- Venue
- Arteriosclerosis Thrombosis and Vascular Biology
- Published
- 2015-08
- Volume
- 35
- Issue
- 8
- Pages
- 1736-1745
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2161264907
- Cited by
- 120
- References
- 49
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 3 · 2021: 6 · 2020: 8 · 2019: 11 · 2018: 17 · 2017: 13 · 2016: 45 · 2015: 14
- FWCI
- 21.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Keywords
- antidotes, oral anticoagulants, dabigatran, rivaroxaban, edoxaban, apixaban, direct thrombin inhibitors, anti-Xa inhibitors, activated carbon, hemodialysis, prothrombin complex concentrate, recombinant factor VIIa, idarucizumab, anticoagulant reversal, hemorrhage
- MeSH terms
- Administration, Oral, Animals, Anticoagulants, Antidotes, Arginine, Blood Coagulation, Coagulants, Hemorrhage, Humans, Piperazines, Risk Factors, Treatment Outcome, Risk Assessment, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
