The impact of a three-factor prothrombin complex concentrate on the anticoagulatory effects of the factor Xa inhibitor edoxaban. Issue 4 (October 2015)

• Record Type: Journal Article
• Authors: Brown, Karen S.; Wickremasingha, Prachi; Parasrampuria, Dolly A.; Weiss, Daniel; Kochan, Jarema; Dishy, Victor; He, Ling; Shi, Minggao
• Is Part Of: Thrombosis research. Volume 136:Issue 4(2015)
• Page Start: 825
• Page End: 831
• Publication Date: 2015-10
• Subjects: Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2015.07.012
• Languages: English
• ISSNs: 0049-3848

Abstract

<abstract abstract-type="author" id="ab0005"> <title id="st0005">Abstract</title> <sec> <title id="st0010">Background</title> <p id="sp0005">Edoxaban, a direct factor Xa inhibitor, is a once-daily, non-vitamin K antagonist oral anticoagulant. There is no established method to reverse the activity of non-vitamin K oral anticoagulants in cases of hemorrhage or urgent surgery. This study evaluated the ability of a 3-factor prothrombin complex concentrate (3F-PCC) to reverse the anticoagulatory effects of edoxaban.</p> </sec> <sec> <title id="st0015">Methods</title> <p id="sp0010">In this phase 1 study, 24 healthy subjects were randomly assigned to receive a single dose of 60 or 180 mg edoxaban, followed by placebo, 25 IU/kg 3F-PCC, or 50 IU/kg 3F-PCC. Edoxaban pharmacokinetics and pharmacodynamics, including the primary endpoint of prothrombin time (PT) and endogenous thrombin potential (ETP), were assessed. D-dimer and prothrombin fragment 1 and 2 (F1+2) were also measured.</p> </sec> <sec> <title id="st0020">Results</title> <p id="sp0015">Overall, there were no apparent consistent effects of 3F-PCC on edoxaban pharmacokinetics. Administration of 3F-PCC 25 or 50 IU/kg with edoxaban 60 or 180 mg did not substantially accelerate the return of PT to baseline levels. However, infusion of 3F-PCC 25 and 50 IU/kg did substantially accelerate return to baseline of ETP compared with placebo. D-dimer and F1+2 data did not indicate any lasting procoagulant effects of 3F-PCC infusion, although a transient increase in F1+2 was noted during and after 3F-PCC infusion. Edoxaban and 3F-PCC co-administration was well tolerated in normal healthy subjects.</p> </sec> <sec> <title id="st0025">Conclusions</title> <p id="sp0020">There was no apparent reversal of PT prolongation with 3F-PCC following edoxaban infusion, but ETP was completely reversed. Co-administration of 3F-PCC was well tolerated, but a dose-dependent increase in F1+2 may reflect a procoagulant risk.</p> </sec> </abstract>