Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants
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 ba...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/rth2.12332 |
| _version_ | 1797711762609405952 |
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| author | Michael Metze Christian Pfrepper Tristan Klöter Stephan Stöbe Roland Siegemund Thomas Siegemund Elvira Edel Ulrich Laufs Sirak Petros |
| author_facet | Michael Metze Christian Pfrepper Tristan Klöter Stephan Stöbe Roland Siegemund Thomas Siegemund Elvira Edel Ulrich Laufs Sirak Petros |
| author_sort | Michael Metze |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T07:11:49Z |
| format | Article |
| id | doaj.art-0b75fd2f634648949da32d83eb8b5647 |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T07:11:49Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-0b75fd2f634648949da32d83eb8b56472023-09-02T23:01:17ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792020-05-014461061810.1002/rth2.12332Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulantsMichael Metze0Christian Pfrepper1Tristan Klöter2Stephan Stöbe3Roland Siegemund4Thomas Siegemund5Elvira Edel6Ulrich Laufs7Sirak Petros8Department of Cardiology Medical Department IV University Hospital Leipzig Leipzig GermanyDivision of Hemostaseology Medical Department I University Hospital Leipzig Leipzig GermanyDepartment of Cardiology Medical Department IV University Hospital Leipzig Leipzig GermanyDepartment of Cardiology Medical Department IV University Hospital Leipzig Leipzig GermanyDivision of Hemostaseology Medical Department I University Hospital Leipzig Leipzig GermanyDivision of Hemostaseology Medical Department I University Hospital Leipzig Leipzig GermanyInstitute of Transfusion Medicine University Hospital Leipzig Leipzig GermanyDepartment of Cardiology Medical Department IV University Hospital Leipzig Leipzig GermanyDivision of Hemostaseology Medical Department I University Hospital Leipzig Leipzig GermanyAbstract 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.https://doi.org/10.1002/rth2.12332anticoagulants/therapeutic useblood coagulationdabigatran/therapeutic usefactor Xa inhibitors/therapeutic usethrombin/analysisthrombin/drug effects |
| spellingShingle | Michael Metze Christian Pfrepper Tristan Klöter Stephan Stöbe Roland Siegemund Thomas Siegemund Elvira Edel Ulrich Laufs Sirak Petros Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants Research and Practice in Thrombosis and Haemostasis anticoagulants/therapeutic use blood coagulation dabigatran/therapeutic use factor Xa inhibitors/therapeutic use thrombin/analysis thrombin/drug effects |
| title | Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants |
| title_full | Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants |
| title_fullStr | Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants |
| title_full_unstemmed | Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants |
| title_short | Inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants |
| title_sort | inhibition of thrombin generation 12 hours after intake of direct oral anticoagulants |
| topic | anticoagulants/therapeutic use blood coagulation dabigatran/therapeutic use factor Xa inhibitors/therapeutic use thrombin/analysis thrombin/drug effects |
| url | https://doi.org/10.1002/rth2.12332 |
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