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Management of bleeding in patients treated with direct oral anticoagulants
BACKGROUND: Recently, a new generation of direct-acting oral anticoagulants (DOACs) with a greater specificity towards activated coagulation factors was introduced based on encouraging results for efficacy and safety in clinical studies. An initial limitation of these new drugs was the absence of an...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992194/ https://www.ncbi.nlm.nih.gov/pubmed/27543264 http://dx.doi.org/10.1186/s13054-016-1413-3 |
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author | Levi, Marcel |
author_facet | Levi, Marcel |
author_sort | Levi, Marcel |
collection | PubMed |
description | BACKGROUND: Recently, a new generation of direct-acting oral anticoagulants (DOACs) with a greater specificity towards activated coagulation factors was introduced based on encouraging results for efficacy and safety in clinical studies. An initial limitation of these new drugs was the absence of an adequate strategy to reverse the effect if a bleeding event occurs or an urgent invasive procedure has to be carried out. MAIN TEXT: Specific reversing agents for DOACs have become available, however, and are now evaluated in clinical studies. For the anti-factor Xa agents (rivaroxaban, apixaban, and edoxaban) a number of studies have shown that the administration of prothrombin complex concentrate resulted in a correction of the prolonged prothrombin time and restored depressed thrombin generation after rivaroxaban treatment in a controlled trial in healthy human subjects. In view of the relatively wide availability of prothrombin complex concentrates, this would be an interesting option if the results can be confirmed in patients on oral factor Xa inhibitors who present with bleeding complications. More specific reversal can be achieved with andexanet, a new agent currently in development that competitively binds to the anti-factor Xa agents. For the direct thrombin inhibitor dabigatran, the administration of prothrombin complex concentrates showed variable results in various volunteer trials and efficacy at relatively high doses in animal studies. Recently, a Fab fragment of a monoclonal antibody (idarucizumab) was shown to be an effective reversal agent for dabigatran in human studies. CONCLUSION: For the new generation of DOACs, several reversal strategies and specific antidotes are under evaluation, although most interventions need further evaluation in clinical trials. |
format | Online Article Text |
id | pubmed-4992194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49921942016-08-21 Management of bleeding in patients treated with direct oral anticoagulants Levi, Marcel Crit Care Review BACKGROUND: Recently, a new generation of direct-acting oral anticoagulants (DOACs) with a greater specificity towards activated coagulation factors was introduced based on encouraging results for efficacy and safety in clinical studies. An initial limitation of these new drugs was the absence of an adequate strategy to reverse the effect if a bleeding event occurs or an urgent invasive procedure has to be carried out. MAIN TEXT: Specific reversing agents for DOACs have become available, however, and are now evaluated in clinical studies. For the anti-factor Xa agents (rivaroxaban, apixaban, and edoxaban) a number of studies have shown that the administration of prothrombin complex concentrate resulted in a correction of the prolonged prothrombin time and restored depressed thrombin generation after rivaroxaban treatment in a controlled trial in healthy human subjects. In view of the relatively wide availability of prothrombin complex concentrates, this would be an interesting option if the results can be confirmed in patients on oral factor Xa inhibitors who present with bleeding complications. More specific reversal can be achieved with andexanet, a new agent currently in development that competitively binds to the anti-factor Xa agents. For the direct thrombin inhibitor dabigatran, the administration of prothrombin complex concentrates showed variable results in various volunteer trials and efficacy at relatively high doses in animal studies. Recently, a Fab fragment of a monoclonal antibody (idarucizumab) was shown to be an effective reversal agent for dabigatran in human studies. CONCLUSION: For the new generation of DOACs, several reversal strategies and specific antidotes are under evaluation, although most interventions need further evaluation in clinical trials. BioMed Central 2016-08-20 /pmc/articles/PMC4992194/ /pubmed/27543264 http://dx.doi.org/10.1186/s13054-016-1413-3 Text en © The Author(s). 2016 Open AccessThis article is 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, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Levi, Marcel Management of bleeding in patients treated with direct oral anticoagulants |
title | Management of bleeding in patients treated with direct oral anticoagulants |
title_full | Management of bleeding in patients treated with direct oral anticoagulants |
title_fullStr | Management of bleeding in patients treated with direct oral anticoagulants |
title_full_unstemmed | Management of bleeding in patients treated with direct oral anticoagulants |
title_short | Management of bleeding in patients treated with direct oral anticoagulants |
title_sort | management of bleeding in patients treated with direct oral anticoagulants |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992194/ https://www.ncbi.nlm.nih.gov/pubmed/27543264 http://dx.doi.org/10.1186/s13054-016-1413-3 |
work_keys_str_mv | AT levimarcel managementofbleedinginpatientstreatedwithdirectoralanticoagulants |