title: Comparison of prothrombin time tests used in the monitoring of edoxaban and their evaluation as indicators of the reversal effect.
abstract: Clinical demand for the prompt assessment of the activity of direct-acting factor Xa inhibitors in the emergency care setting is increasing. In the present study, we examined whether prothrombin time (PT) tests can serve as a clinically useful indicator of anti-factor Xa activity. In the first series, the in vitro effect of edoxaban on PT was evaluated by spiking human plasma with edoxaban and measuring PT using three different commercial PT tests. In the second series, the reversal effect of prothrombin complex concentrates (PCC) and activated PCC (aPCC) in edoxaban-spiked plasma was evaluated. In the third series, PT of plasma samples from patients administered either 15 or 30 mg/day of edoxaban was assessed, and the results were compared with edoxaban concentrations determined by a calibrated anti-factor Xa activity assay. The spike test revealed that all PT reagents positively correlated with edoxaban. The sensitivity to edoxaban varied among the three reagents and Triniclot(®) Excel S showed the best performance. Prolonged PT by edoxaban was reversed by PCC and aPCC in a dose-dependent manner; however, complete reversal was not achieved. Positive correlation between anti-factor Xa activity and PT was shown in the clinical samples at the edoxaban range from 0 to >300 ng/mL.
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan. toshiiba@juntendo.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Iba
authors.affiliation: Scientific and Technical Support Department, Kyowa Medex Co., Ltd., Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Emmi
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hiki
authors.affiliation: Department of Orthopaedics, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nagayama
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Aihara
authors.affiliation: Department of Clinical Laboratory Medicine, Juntendo University School Medicine, Tokyo, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tabe
authors.affiliation: Division of Clinical Laboratory, Juntendo University Hospital, Tokyo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Yuri
authors.affiliation: Division of Clinical Laboratory, Juntendo University Hospital, Tokyo, Japan.
authors.forename: Akimichi
authors.initials: A
authors.lastname: Ohsaka
mesh_terms: D001779:Blood Coagulation Factors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D065427:Factor Xa Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D011517:Prothrombin Time; D011725:Pyridines / Q000097:blood* / Q000494:pharmacology; D013844:Thiazoles / Q000097:blood* / Q000494:pharmacology
chemical_list: D001779:Blood Coagulation Factors; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; C025667:prothrombin complex concentrates; C552171:edoxaban
keywords: Anti-factor Xa activity; Edoxaban; Prothrombin complex concentrates, activated prothrombin complex concentrates; Prothrombin time