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Current evidence of oral anticoagulant reversal : A systematic review

Tornkvist, Max; Smith, J. Gustav LU and Labaf, Ashkan LU (2018) In Thrombosis Research 162. p.22-31
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Direct oral anticoagulants, Oral anticoagulant, Reversal, Vitamin K antagonists
in
Thrombosis Research
volume
162
pages
10 pages
publisher
Elsevier Ltd
external identifiers
  • scopus:85038120185
ISSN
0049-3848
DOI
10.1016/j.thromres.2017.12.003
language
English
LU publication?
yes
id
f06b001f-0776-47ae-830e-5efb5fbb132a
date added to LUP
2018-01-02 11:43:37
date last changed
2018-10-16 05:22:25
@article{f06b001f-0776-47ae-830e-5efb5fbb132a,
  abstract     = {<p>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 &lt; 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.</p>},
  author       = {Tornkvist, Max and Smith, J. Gustav and Labaf, Ashkan},
  issn         = {0049-3848},
  keyword      = {Direct oral anticoagulants,Oral anticoagulant,Reversal,Vitamin K antagonists},
  language     = {eng},
  month        = {02},
  pages        = {22--31},
  publisher    = {Elsevier Ltd},
  series       = {Thrombosis Research},
  title        = {Current evidence of oral anticoagulant reversal : A systematic review},
  url          = {http://dx.doi.org/10.1016/j.thromres.2017.12.003},
  volume       = {162},
  year         = {2018},
}