Reversal of Oral Anticoagulation

Abstract

Although the use of dabigatran and rivaroxaban are increasing, data on reversal of their effects are limited. The lack of reliable monitoring methods and specific reversal agents renders treatment strategies empirical and as a result, , treatment consists mainly of supportive measures. Therefore, we performed a systematic search of the PubMed database to find studies and reviews pertaining to oral anticoagulation reversal strategies. This review discusses current anticoagulation reversal recommendations for the oral anticoagulants warfarin, dabigatran, and rivaroxaban for patients at a heightened risk of bleeding, actively bleeding or those in need for pre-procedural anticoagulation reversal. We highlight the literature that shaped these recommendations and provide directions for future research to address knowledge gaps. While reliable recommendations are available for anticoagulation reversal in patients treated with warfarin, guidance on reversal of dabigatran and rivaroxaban is varied and equivocal. Given the increasing use of the newer agents, focused research is needed to identify effective reversal strategies and develop and implement an accurate method (assay) to guide reversal of the newer agents. Determining patient-specific factors that influence the effectiveness of reversal treatments and comparing the effectiveness of various treatment strategies are pertinent areas for future anticoagulation reversal research.

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“…Second, there are no direct acting antidotes for either dabigatran or any of the FⅩa inhibitors. Nevertheless, recommendations have been made in treatment guidelines regarding how to manage anticoagulation reversal of the new agents, and several recent reviews on the topic have been published [91][92][93] . Moreover, some groups have offered consensus expert opinions by the authors regarding optimal approaches for anticoagulation reversal of the new agents [93,94] .…”

“…The thrombin time (TT) test is affected by dabigatran but is very sensitive to the drug effects, rendering it a qualitative measure at typical drug concentrations. However, it can be used to exclude a dabigatran drug effect [92,95,96] . Liew et al [96] suggested a normal aPTT result combined with a prolonged TT indicated low anticoagulation intensity with dabigatran, whereas prolonged results for both tests would indicate full anticoagulation.…”

“…However, the assay must be modified with calibrators specific to the given FⅩa inhibitor. Calibrators for the new drugs are becoming available and the test will likely emerge as the preferred measure of anticoagulation intensity associated with the FⅩa inhibitors [92,93,95,96] .…”

“…One caveat that must be remembered is the effect of renal insufficiency to slow elimination, particularly with dabigatran [91] . Several investigators have offered suggestions for timing of the discontinuation of the new oral anticoagulants before an elective or nonemergent surgery [92,93,100] . Anticoagulation reversal of a TSOA in the patient with moderate to severe bleeding or in need of urgent surgery is more challenging.…”

“…Both of the modalities appear as recommendations for dabigatran removal by consensus groups [93,94,104] . However, while these methods are effective to remove dabigatran and presumably reverse its anticoagulant effect, both have limited application since availability is low, vascular access is required, and the time to implement is often prolonged [92][93][94]96] . In contrast, high protein binding characterizes rivaroxaban (92%-95%) and apixaban (84%-87%), meaning a significant amount of either drug is unlikely to be removed by hemodialysis or hemoperfusion [93,94] .…”