Overview of direct oral anticoagulant therapy reversal

Gulseth, Michael P.

doi:10.2146/ajhp150966

Cited by 12 publications

(8 citation statements)

References 44 publications

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“…The resulting shorter turnaround times (5-10 min vs. 30-45 min for ecarin CT vs. diluted thrombin time) may allow for an expedited diagnosis in order to initiate emergency treatment. This would be in line with current guidelines for the management of bleeding events or urgent surgery, which recommend laboratory testing of the dabigatran concentration and dabigatran effects prior to reversal [15][16][17][18][19].…”

Section: Measurement Of Dabigatran With Thromboelastometrysupporting

confidence: 71%

In vitro and ex vivo Measurement of Prophylactic Dabigatran Concentrations with a New Ecarin-Based Thromboelastometry Test

Körber

Langer

Köhr

et al. 2017

Transfus Med Hemother

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Background: An increasing number of oral anticoagulants has been approved, including dabigatran etexilate (DE). DE is a direct thrombin inhibitor that requires no routine monitoring, but, if necessary (e.g. urgent surgery etc.), the diluted thrombin time measured with Hemoclot® has shown reliable results. So far, no point-of-care (PoC) assay is available to measure DE effects. The EcaTEM assay uses ecarin to initiate the coagulation cascade at the step of thrombin generation and measures the clotting time (CT) by thromboelastometry. Methods: This study investigated the correlation of the EcaTEM with standard laboratory assays in dabigatran-treated patients. Ten patients undergoing total hip or knee arthroplasty were included in the study. DE for thromboprophylaxis was started 4 h after surgery. Blood samples were taken before surgery as well as 2, 6 and 12 h after ingestion on the 3rd postoperative day. Dabigatran concentration (Hemoclot), activated partial thromboplastin time, thrombin time and CT EcaTEM were measured. Results: Only CT EcaTEM and Hemoclot showed a correlation > 0.75 for all measurements. Conclusion: CT EcaTEM appears a valid PoC method parameter to detect thrombin inhibition and thus the presence of dabigatran beside diluted thrombin time at different concentration levels. This may represent an opportunity to identify the presence of dabigatran, e.g., in emergency situations.

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Section: Measurement Of Dabigatran With Thromboelastometrysupporting

confidence: 71%

In vitro and ex vivo Measurement of Prophylactic Dabigatran Concentrations with a New Ecarin-Based Thromboelastometry Test

Körber

Langer

Köhr

et al. 2017

Transfus Med Hemother

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“…Therefore, reversal of the effects of FXa inhibitors may be necessary in the event of spontaneous or traumatic bleeding, or if a patient requires urgent surgery. 7 Andexanet alfa (andexanet) is a modified human FXa approved in the United States and European Union as a specific reversal agent for patients treated with apixaban or rivaroxaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. 8,9 Andexanet rapidly binds and sequesters FXa inhibitors, reduces the anticoagulant activity, and restores endogenous FXa activity.…”

Section: Introductionmentioning

confidence: 99%

Andexanet versus prothrombin complex concentrates: Differences in reversal of factor Xa inhibitors in in vitro thrombin generation

Lin

Bui

et al. 2020

Research and Practice in Thrombosis and Haemostasis

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Background Andexanet alfa (andexanet) is a modified human factor Xa (FXa) approved for anticoagulation reversal in patients with life‐threatening bleeding treated with rivaroxaban or apixaban. Four‐factor prothrombin complex concentrates (4F‐PCCs) are approved for reversal of vitamin K antagonist–induced anticoagulation but not FXa inhibitors. The mechanism and effectiveness of 4F‐PCCs for FXa inhibitor reversal are unclear. Objective To investigate the mechanism and impact of 4F‐PCCs on reversal of rivaroxaban and apixaban in vitro compared to andexanet. Methods The effect of 4F‐PCCs (or individual factors) on tissue factor‐initiated thrombin generation (TF‐TG) was evaluated in human plasma, with or without rivaroxaban or apixaban, and compared with andexanet under the same conditions. Results In the TF‐TG assay, 4F‐PCC completely reversed warfarin anticoagulation. Andexanet normalized TF‐TG over a wide range of apixaban and rivaroxaban concentrations tested (19‐2000 ng/mL). However, 4F‐PCC (or individual factors) was unable to normalize endogenous thrombin potential (ETP) or peak thrombin (Peak) in the presence of apixaban or rivaroxaban (75‐500 ng/mL). TF‐TG was only normalized by 4F‐PCC at inhibitor concentrations <75 ng/mL (ETP) or <37.5 ng/mL (Peak). These data can be explained by the estimated thresholds of FXa activity required to support normal TF‐TG based on the inhibitor:FXa ratios and levels of uninhibited FXa. The data are consistent with healthy volunteer studies where TF‐TG is not normalized until inhibitor levels are substantially decreased. Conclusions Both the theoretical calculations and experimental data demonstrated that 4F‐PCCs are only able to normalize TG over a low and narrow range of FXa inhibitor concentrations (<75 ng/mL).

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“…Ultimately, more data are needed to determine the risks versus benefits of 4F‐PCC in the optimal dosing of 4F‐PCC and the management of severe bleeding from DOACs. Recently, there is a proposed management algorithm for patients on DOACs based on urgency, including the use of alternative reversal agent such as activated charcoal, although the algorithm lacks dosing recommendation for 4F‐PCC, any information in regard to the pipeline factor Xa inhibitor antidote such as andexanet alfa, and any concrete evidence supporting its use .…”

Section: Discussionmentioning

confidence: 99%

Use of four‐factor prothrombin complex concentrate for the mitigation of rivaroxaban‐induced bleeding in an emergent coronary artery bypass graft

Liu

Aguele

Darr

2017

Clinical Case Reports

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Key Clinical MessageWe presented the first case of four‐factor prothrombin complex concentrate (4F‐PCC) for the alleviation of bleeding for emergent on‐pump coronary artery bypass graft (CABG) with the patient discharged by postoperative day (POD) 9 with no sequelae. Until direct antidotes are available, 4F‐PCC may play a role in the management of mitigating rivaroxaban‐induced bleeding in surgical procedure.

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Overview of direct oral anticoagulant therapy reversal

Abstract: Purpose. strategies for the management of bleeding complications and facilitation of an invasive procedure in patients receiving direct oral anticoagulants (DoaCs) are reviewed.

Cited by 12 publications

References 44 publications

In vitro and ex vivo Measurement of Prophylactic Dabigatran Concentrations with a New Ecarin-Based Thromboelastometry Test

In vitro and ex vivo Measurement of Prophylactic Dabigatran Concentrations with a New Ecarin-Based Thromboelastometry Test

Andexanet versus prothrombin complex concentrates: Differences in reversal of factor Xa inhibitors in in vitro thrombin generation

Use of four‐factor prothrombin complex concentrate for the mitigation of rivaroxaban‐induced bleeding in an emergent coronary artery bypass graft

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