International Journal of Hematology

, Volume 103, Issue 6, pp 665–672 | Cite as

Comparison of prothrombin time tests used in the monitoring of edoxaban and their evaluation as indicators of the reversal effect

  • Toshiaki Iba
  • Mari Emmi
  • Makoto Hiki
  • Masataka Nagayama
  • Koichiro Aihara
  • Yoko Tabe
  • Maiko Yuri
  • Akimichi Ohsaka
Original Article


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.


Prothrombin time Anti-factor Xa activity Edoxaban Prothrombin complex concentrates, activated prothrombin complex concentrates 


Compliance with ethical standard

Conflict of interest

Emmi M. works for Kyowa Medex Co. Ltd. The other authors state that they have no conflict of interests.


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Copyright information

© The Japanese Society of Hematology 2016

Authors and Affiliations

  • Toshiaki Iba
    • 1
  • Mari Emmi
    • 2
  • Makoto Hiki
    • 1
  • Masataka Nagayama
    • 3
  • Koichiro Aihara
    • 1
  • Yoko Tabe
    • 4
  • Maiko Yuri
    • 5
  • Akimichi Ohsaka
    • 5
  1. 1.Department of Emergency and Disaster MedicineJuntendo University School of MedicineTokyoJapan
  2. 2.Scientific and Technical Support DepartmentKyowa Medex Co., Ltd.TokyoJapan
  3. 3.Department of OrthopaedicsJuntendo University School of MedicineTokyoJapan
  4. 4.Department of Clinical Laboratory MedicineJuntendo University School MedicineTokyoJapan
  5. 5.Division of Clinical LaboratoryJuntendo University HospitalTokyoJapan

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