Monitoring the Effects and Antidotes of the Non-vitamin K Oral Anticoagulants

Abstract

In the last decade, we have witnessed the emergence of the oral non-vitamin K oral anticoagulants (NOACs), which have numerous advantages compared with the vitamin K antagonists, particularly their lack of need for monitoring; as a result their use is increasing. Nonetheless, the NOACs face two major challenges: the need for reliable laboratory assays to assess their anticoagulation effect, and the lack of approved antidotes to reverse their action. This article provides an overview of monitoring the anticoagulant effect of NOACs and their potential specific antidotes in development.

Rationale and design of a phase III safety trial of idarucizumab in children receiving dabigatran etexilate for venous thromboembolism

“…The current management of symptomatic bleeding associated with dabigatran has some similarities to that observed in patients taking VKA, such as the cessation of anticoagulant treatment and the use of supportive care guided towards hemodynamic stabilization. In addition, hemodialysis may represent an option to expedite the removal of systemic dabigatran 36. Specific reversal agents for DOACs may be advantageous in managing serious bleeding or when a rapid reversal of DOAC effect is required 37.…”

“…Therapeutic guidelines for treatment of VTE in children are based on a limited number of small pediatric trials but, in many cases, the guidelines are extrapolated from adult studies, which may be inappropriate 37. In addition, guidelines recommend generic methods, such as use of gastric lavage and oral activated charcoal in case of anticoagulant overdose, use of fresh frozen plasma or activated prothrombin complex concentrate in case of serious bleeding, and performing dialysis to reverse the anticoagulant effects of dabigatran 36, 42. Nevertheless, although experience is very limited with the use of reversal agents in children receiving anticoagulants, anecdotal evidence from a case report has demonstrated the potential utility of idarucizumab in children with overdose of dabigatran.…”

“…These assays can give an objective measure of the reversal of anticoagulation. dTT and ECT are appropriate for dabigatran as the correlation between these parameters and dabigatran plasma concentration showed a high degree of linearity 36. Bleeding assessment is a more subjective metric, and is dependent upon the initial bleeding event or procedure, the presence of damaged blood vessels, timing, and patient characteristics.…”

“…In addition, hemodialysis may represent an option to expedite the removal of systemic dabigatran. 36 Specific reversal agents for DOACs may be advantageous in managing serious bleeding or when a rapid reversal of DOAC effect is required. 37 With the approval of idarucizumab, a dabigatran-specific reversal agent, an additional treatment option during emergency situations is available.…”

“…37 In addition, guidelines recommend generic methods, such as use of gastric lavage and oral activated charcoal in case of anticoagulant overdose, use of fresh frozen plasma or activated prothrombin complex concentrate in case of serious bleeding, and performing dialysis to reverse the anticoagulant effects of dabigatran. 36,42 Nevertheless, although experience is very limited with the use of reversal agents in children receiving anticoagulants, anecdotal evidence from a case report has demonstrated the potential utility of idarucizumab in children with overdose of dabigatran. For example, a case report that involved a 15-year-old girl who presented with dabigatran overdose demonstrated that use of idarucizumab (5 g) completely and immediately reversed the anticoagulant effects of excess dabigatran (>1000 ng/mL).…”