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Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban.
Clin Res Cardiol. 2013 Jun; 102(6):399-412.CR

Abstract

Dabigatran, apixaban, and rivaroxaban have been approved for primary and secondary stroke prevention in patients with atrial fibrillation. However, questions have arisen about how to manage emergency situations, such as when thrombolysis would be required for acute ischemic stroke or for the managing intracranial or gastrointestinal bleedings. We summarize the current literature and provide recommendations for the management of these situations. Peak plasma levels of the direct oral anticoagulants (DOACs) apixaban, dabigatran, or rivaroxaban are observed about 2-4 h after intake. Elimination of dabigatran is mainly dependent on renal function. Consequently, if renal function is impaired, there is a risk of drug accumulation that is highest for dabigatran followed by rivaroxaban and then apixaban and thus dosing recommendations are different. To date, no bedside tests are available that reliably assess the anticoagulatory effect of DOACs, nor are specific antidotes available. We recommend performing the following tests if DOAC intake is unknown: dabigatran-associated bleeding risk is minimized or can be neglected if thrombin time, Hemoclot test, or Ecarin clotting time is normal. Apixaban and rivaroxaban effects can be ruled out if findings from the anti-factor Xa activity test are normal. High plasma levels of DOAC are also mostly excluded if PTT and PTZ are normal four or more hours after DOAC intake. However, normal values of global coagulation tests are not sufficient if thrombolysis is indicated for treating acute stroke. The decision for or against thrombolysis is an individual decision; in these cases, thrombolysis use is off-label. In case of bleeding, prothrombin complex concentrates seems to be the most plausible treatment. For severe gastrointestinal bleeding with life-threatening blood loss, the bleeding source needs to be identified and treated by invasive measures. Use of procoagulant drugs (antifibrinolytics) might also be considered. However, there is very limited clinical experience with these products in conjunction with DOAC.

Authors+Show Affiliations

Neurologische Klinik, Klinikum Frankfurt Höchst, Frankfurt am Main, Germany. Thorsten.Steiner@KlinikumFrankfurt.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23669868

Citation

Steiner, T, et al. "Recommendations for the Emergency Management of Complications Associated With the New Direct Oral Anticoagulants (DOACs), Apixaban, Dabigatran and Rivaroxaban." Clinical Research in Cardiology : Official Journal of the German Cardiac Society, vol. 102, no. 6, 2013, pp. 399-412.
Steiner T, Böhm M, Dichgans M, et al. 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.
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. (2013). Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. Clinical Research in Cardiology : Official Journal of the German Cardiac Society, 102(6), 399-412. https://doi.org/10.1007/s00392-013-0560-7
Steiner T, et al. 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. PubMed PMID: 23669868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. AU - Steiner,T, AU - Böhm,M, AU - Dichgans,M, AU - Diener,H-C, AU - Ell,C, AU - Endres,M, AU - Epple,C, AU - Grond,M, AU - Laufs,U, AU - Nickenig,G, AU - Riess,H, AU - Röther,J, AU - Schellinger,P D, AU - Spannagl,M, AU - Veltkamp,R, Y1 - 2013/05/14/ PY - 2013/02/06/received PY - 2013/03/21/accepted PY - 2013/5/15/entrez PY - 2013/5/15/pubmed PY - 2013/12/16/medline SP - 399 EP - 412 JF - Clinical research in cardiology : official journal of the German Cardiac Society JO - Clin Res Cardiol VL - 102 IS - 6 N2 - Dabigatran, apixaban, and rivaroxaban have been approved for primary and secondary stroke prevention in patients with atrial fibrillation. However, questions have arisen about how to manage emergency situations, such as when thrombolysis would be required for acute ischemic stroke or for the managing intracranial or gastrointestinal bleedings. We summarize the current literature and provide recommendations for the management of these situations. Peak plasma levels of the direct oral anticoagulants (DOACs) apixaban, dabigatran, or rivaroxaban are observed about 2-4 h after intake. Elimination of dabigatran is mainly dependent on renal function. Consequently, if renal function is impaired, there is a risk of drug accumulation that is highest for dabigatran followed by rivaroxaban and then apixaban and thus dosing recommendations are different. To date, no bedside tests are available that reliably assess the anticoagulatory effect of DOACs, nor are specific antidotes available. We recommend performing the following tests if DOAC intake is unknown: dabigatran-associated bleeding risk is minimized or can be neglected if thrombin time, Hemoclot test, or Ecarin clotting time is normal. Apixaban and rivaroxaban effects can be ruled out if findings from the anti-factor Xa activity test are normal. High plasma levels of DOAC are also mostly excluded if PTT and PTZ are normal four or more hours after DOAC intake. However, normal values of global coagulation tests are not sufficient if thrombolysis is indicated for treating acute stroke. The decision for or against thrombolysis is an individual decision; in these cases, thrombolysis use is off-label. In case of bleeding, prothrombin complex concentrates seems to be the most plausible treatment. For severe gastrointestinal bleeding with life-threatening blood loss, the bleeding source needs to be identified and treated by invasive measures. Use of procoagulant drugs (antifibrinolytics) might also be considered. However, there is very limited clinical experience with these products in conjunction with DOAC. SN - 1861-0692 UR - https://www.unboundmedicine.com/medline/citation/23669868/Recommendations_for_the_emergency_management_of_complications_associated_with_the_new_direct_oral_anticoagulants__DOACs__apixaban_dabigatran_and_rivaroxaban_ L2 - https://dx.doi.org/10.1007/s00392-013-0560-7 DB - PRIME DP - Unbound Medicine ER -