INTRODUCTION: Approximately 4-6% of patients treated with oral anticoagulants (OAC) will suffer from major hemorrhage or be in need of urgent surgery necessitating anticoagulant reversal therapy. Several new oral anticoagulants and reversal agents have been introduced that make it difficult for physicians to stay updated on the current evidence of reversal management. This study aims to review the recent literature on oral anticoagulation reversal therapy and to present the current evidence in an easily approachable manner.
MATERIALS AND METHODS: A systematic literature search was conducted using PubMed and EMBASE to identify the latest publications on both vitamin K antagonist (VKA) and direct oral anticoagulant (DOAC) reversal strategies. All studies on humans who received any acute reversal management of VKA treatment were included, except case studies. Since only two studies on acute reversal of DOAC treatment have been published, clinical trials on healthy volunteers were also included.
RESULTS: Twenty-one studies with a total of 4783 VKA treated patients, and 12 studies with a total of 529 DOAC treated patients were included. Elevated INR values due to VKA treatment could be reversed (INR=1.5) in 63.1% (95% CI: 61.0-65.2) of study subjects after treatment with 4F-PCC, as compared with 12.2% (95% CI: 8.2-16.2) after treatment with fresh frozen plasma (FFP), (p<0.001). Thromboembolism occurred in 1.6% (95% CI: 1.2-2.1) of VKA-patients treated with 4F-PCC, and in 4.5% (95% CI: 2.3-6.7) of FFP-treated patients. To date, reversal of laboratory parameters has been demonstrated for two reversal agents specific to DOACs: idarucizumab for dabigatran reversal and andexanet-alfa for factor Xa-inhibitor reversal.
CONCLUSIONS: This review supports the use of PCC for VKA reversal, specifically for 4F-PCC over FFP for laboratory reversal. There are no studies on clinical efficacy of non-specific agents for DOAC reversal and the evidence for laboratory reversal is not consistent.
This article presents the state of the literature around reversal of VKAs and DOAC, in large part in the setting of bleeding. The authors are upfront about the limitations of the pooled data given heterogeneity, etc. I think it's useful for clinicians to know the state of things. Lots of interest in the evidence for reversal of DOACs to be sure, and I think people would find the VKA reversal data interesting. I think some may be less familiar with 4F-PCC than with FFP.
Well done systematic review of a subject about which most EM physicians already know.