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Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants.
Res Pract Thromb Haemost. 2020 May; 4(4):610-618.RP

Abstract

Background

The residual antithrombotic activity 12 hours after intake of direct oral anticoagulants (DOACs) is of clinical relevance in the setting of bleeding or urgent surgery.

Objective

To evaluate the effects of DOACs on thrombin generation 12 hours after DOAC intake in comparison to baseline and a healthy control group.

Methods

Eighty patients were recruited, 20 patients for each approved DOAC: apixaban, edoxaban, rivaroxaban, and dabigatran. The patients were either to be put on anticoagulation for the first time or had stopped taking oral anticoagulation for at least 48 hours. Blood plasma was sampled before (baseline) and 12 hours after starting DOAC for quantification of drug levels and thrombin generation assayed using an automated system (ST Genesia). Sixty-one blood donors served as control group.

Results

The factor Xa inhibitors significantly increased lag time (137%-219%) and reduced thrombin peak (47%-76%) and velocity index (17%-44%) after 12 hours compared to baseline. Dabigatran showed prolongation of lag time to 133% and time to peak to 119%. All patients had residual antithrombotic activity, with reduced thrombin generation parameters 12 hours after DOAC intake compared to baseline and to the healthy control group. This effect remained significant in patients with low residual DOAC plasma levels <50 ng/mL.

Conclusion

Thrombin generation remains reduced 12 hours after DOAC intake. While thrombin peak is particularly modified by factor Xa inhibitors, all DOACs prolong the lag time and time to thrombin peak. In the setting of bleeding or urgent surgery, the automated thrombin generation assay may assist in decision making and antidote administration.

Authors+Show Affiliations

Department of Cardiology Medical Department IV University Hospital Leipzig Leipzig Germany.Division of Hemostaseology Medical Department I University Hospital Leipzig Leipzig Germany.Department of Cardiology Medical Department IV University Hospital Leipzig Leipzig Germany.Department of Cardiology Medical Department IV University Hospital Leipzig Leipzig Germany.Division of Hemostaseology Medical Department I University Hospital Leipzig Leipzig Germany.Division of Hemostaseology Medical Department I University Hospital Leipzig Leipzig Germany.Institute of Transfusion Medicine University Hospital Leipzig Leipzig Germany.Department of Cardiology Medical Department IV University Hospital Leipzig Leipzig Germany.Division of Hemostaseology Medical Department I University Hospital Leipzig Leipzig Germany. Medical ICU University Hospital Leipzig Leipzig Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32548560

Citation

Metze, Michael, et al. "Inhibition of Thrombin Generation 12 hours After Intake of Direct Oral Anticoagulants." Research and Practice in Thrombosis and Haemostasis, vol. 4, no. 4, 2020, pp. 610-618.
Metze M, Pfrepper C, Klöter T, et al. Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants. Res Pract Thromb Haemost. 2020;4(4):610-618.
Metze, M., Pfrepper, C., Klöter, T., Stöbe, S., Siegemund, R., Siegemund, T., Edel, E., Laufs, U., & Petros, S. (2020). Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants. Research and Practice in Thrombosis and Haemostasis, 4(4), 610-618. https://doi.org/10.1002/rth2.12332
Metze M, et al. Inhibition of Thrombin Generation 12 hours After Intake of Direct Oral Anticoagulants. Res Pract Thromb Haemost. 2020;4(4):610-618. PubMed PMID: 32548560.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants. AU - Metze,Michael, AU - Pfrepper,Christian, AU - Klöter,Tristan, AU - Stöbe,Stephan, AU - Siegemund,Roland, AU - Siegemund,Thomas, AU - Edel,Elvira, AU - Laufs,Ulrich, AU - Petros,Sirak, Y1 - 2020/04/23/ PY - 2019/11/20/received PY - 2020/01/12/revised PY - 2020/02/02/accepted PY - 2020/6/18/entrez PY - 2020/6/18/pubmed PY - 2020/6/18/medline KW - anticoagulants/therapeutic use KW - blood coagulation KW - dabigatran/therapeutic use KW - factor Xa inhibitors/therapeutic use KW - thrombin/analysis KW - thrombin/drug effects SP - 610 EP - 618 JF - Research and practice in thrombosis and haemostasis JO - Res Pract Thromb Haemost VL - 4 IS - 4 N2 - Background: The residual antithrombotic activity 12 hours after intake of direct oral anticoagulants (DOACs) is of clinical relevance in the setting of bleeding or urgent surgery. Objective: To evaluate the effects of DOACs on thrombin generation 12 hours after DOAC intake in comparison to baseline and a healthy control group. Methods: Eighty patients were recruited, 20 patients for each approved DOAC: apixaban, edoxaban, rivaroxaban, and dabigatran. The patients were either to be put on anticoagulation for the first time or had stopped taking oral anticoagulation for at least 48 hours. Blood plasma was sampled before (baseline) and 12 hours after starting DOAC for quantification of drug levels and thrombin generation assayed using an automated system (ST Genesia). Sixty-one blood donors served as control group. Results: The factor Xa inhibitors significantly increased lag time (137%-219%) and reduced thrombin peak (47%-76%) and velocity index (17%-44%) after 12 hours compared to baseline. Dabigatran showed prolongation of lag time to 133% and time to peak to 119%. All patients had residual antithrombotic activity, with reduced thrombin generation parameters 12 hours after DOAC intake compared to baseline and to the healthy control group. This effect remained significant in patients with low residual DOAC plasma levels <50 ng/mL. Conclusion: Thrombin generation remains reduced 12 hours after DOAC intake. While thrombin peak is particularly modified by factor Xa inhibitors, all DOACs prolong the lag time and time to thrombin peak. In the setting of bleeding or urgent surgery, the automated thrombin generation assay may assist in decision making and antidote administration. SN - 2475-0379 UR - https://www.unboundmedicine.com/medline/citation/32548560/Inhibition_of_thrombin_generation_12 hours_after_intake_of_direct_oral_anticoagulants L2 - https://doi.org/10.1002/rth2.12332 DB - PRIME DP - Unbound Medicine ER -
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