Enhanced Elimination of Dabigatran Through Extracorporeal Methods

Abstract

Several pharmacokinetic studies have suggested that dabigatran possesses a number of ideal properties for expedited removal via extracorporeal methods. However, this practice has not been prospectively evaluated in patients with life-threatening bleeding or requiring emergency surgery secondary to dabigatran-associated coagulopathy. The purpose of this literature review is to evaluate the published evidence surrounding extracorporeal removal of dabigatran in the setting of emergency surgery or life-threatening bleeding. A query of MEDLINE, Web of Science, International Pharmaceutical Abstracts, and Google Scholar using the terms dabigatran, dabigatran etexilate, hemodialysis, renal replacement therapy, hemorrhage, and atrial fibrillation was used to retrieve relevant literature. Furthermore, a manual search of the references of the identified literature was performed to capture additional data. Current evidence suggests that extracorporeal removal of dabigatran may play a role in the setting of life-threatening bleeding and emergent surgery. Conflicting evidence exists with regard to the potential for redistribution based on serum dabigatran concentrations. In addition, a number of practicalities must be considered before incorporating this technique in the clinical setting. Extracorporeal removal of dabigatran may be a treatment modality in selected patients who require emergency reversal.

Life-threatening bleeding due to persistent dabigatran effect in a patient with sepsis despite idarucizumab therapy and haemodialysis

“…This is a case of significant coagulopathy with re-emergence of dabigatran effect despite attempts to neutralise the drug using the novel specific reversal agent idarucizumab, and the concurrent use of haemodiafiltration, which has been accepted as a method for dabigatran removal in cases of toxicity 4 8 9. There were confounding factors related to the coagulopathy in this case, particularly in the first 24–48 hours when it is extremely likely that DIC and dilutional coagulopathy were coexistent; however, laboratory values demonstrate an elevated level of dabigatran present in the blood at a much later date.…”

“…It undergoes 35% protein binding and has a moderate volume of distribution of 50–70 L 1. It has been documented that there is a rebound increase of plasma dabigatran levels following both idarucizumab treatment and dialysis 4 5. This is thought to be due to redistribution of extravascular dabigatran down its concentration gradient along with uncoupling from plasma proteins 4–6.…”

“…In the past, there has been no specific reversal agent for patients taking dabigatran. Methods used to reverse the activity of dabigatran have included the use of fresh frozen plasma (FFP), prothrombin complex concentrates (eg, prothombinex), activated prothrombin complex concentrates (eg, factor eight inhibitor bypassing fraction (FEIBA))3 and haemodialysis 4. Idarucizumab is now available for use as a dabigatran reversal agent.…”

Idarucizumab for dabigatran overdose

“…Furthermore, dabigatran removal with this technique is slow and incomplete. [5,6] In a reported case series, dabigatran concentrations decreased by 52-77% during hemodialysis. [7] However, in many cases, a rebound effect was observed.…”

“…[7] However, in many cases, a rebound effect was observed. [5,7] The administration of coagulation factors, such as three-or four-factor prothrombin complex concentrates (PCCs) or activated PCCs (aPCCs), may support hemostasis in case of bleeding. High doses of (a)PCCs are recommended to counteract the anticoagulant effect of dabigatran.…”