Review Article| Volume 162, P22-31, February 2018

Current evidence of oral anticoagulant reversal: A systematic review

Published:December 06, 2017DOI:


      • The use of PCC for VKA-associated INR elevation is effective and well-studied.
      • Use of Four factor-PCC is superior to FFP for reversal of VKA-associated INR elevation.
      • There are no studies on clinical efficacy of non-specific agents for DOAC reversal.



      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.


      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.


      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.


      OAC (Oral anticoagulant), VKA (Vitamin K antagonist), DOAC (Direct oral anticoagulant), PCC (Prothrombin complex concentrate), 4F-PCC (Four factor PCC), 3F-PCC (Three factor PCC), aPCC (Activated PCC), FFP (Fresh frozen plasma), AF (Atrial fibrillation), TE (Thromboembolism), VTE (Venous thromboembolism), FIIa (Activated factor II), FXa (Activated factor X), rFVIIa (Recombinant activated factor VII), TTR (Time in therapeutic range), PT (Prothrombin time), INR (International Normalized Ratio), aPTT (Activated partial thromboplastin time), ECT (Ecarin clotting time), ETP (Endogenous thrombin potential), dTT (Diluted thrombin time), ICH (Intracranial hemorrhage), SBU (Statens beredning för medicinsk och social utvärdering (Swedish Agency for Health Technology Assessment and Assessment of Social Services)), SEK (Swedish kronor)


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