title: Prothrombin Time Tests for the Monitoring of Direct Oral Anticoagulants and Their Evaluation as Indicators of the Reversal Effect.
abstract: BACKGROUND
  The prompt assessment and the reversal of direct oral anticoagulants (DOACs) are urgent matters in the emergency care setting. Thus, we planned to elucidate the adequate prothrombin time (PT) test for the evaluation of the anticoagulant effects of various DOACs.
  
  
  METHODS
  The anticoagulant effects of rivaroxaban, apixaban, and edoxaban were measured with 3 PT tests (Triniclot PT Excel S, Neoplastin R, and Thromborel S). Human plasma was spiked with each DOAC at a range of 0 to 1000 ng/mL, and the PT was measured using each PT test. In another series, the reversal effect of either 4-factor prothrombin complex concentrate (PCC) or activated PCC (aPCC) was evaluated with each PT test.
  
  
  RESULTS
  All PT reagents correlated with the concentrations of each DOAC, however, the reactivity was considerably different between the DOACs and the PT tests. A prolonged PT with DOACs was reversed both by PCC and aPCC in a dose-dependent manner; however, Triniclot PT Excel S showed reprolongation of the PT with a higher dose of PCC.
  
  
  CONCLUSIONS
  The proper choice of PT test is necessary for the assessments of the anticoagulant activity of DOACs. It is also important to understand the different characteristics of each PT test for the assessment of the reversal effects of PCC.
authors.affiliation: 1 Department of Surgery, Juntendo University Urayasu Hospital, Urayasu, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nagakari
authors.affiliation: 2 Scientific and Technical Support Department, Kyowa Medex Co, Ltd, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Emmi
authors.affiliation: 3 Department of Emergency and Disaster Medicine, Juntendo University School of Medicine, Bunkyo-ku, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Iba
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000494:pharmacology; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D011517:Prothrombin Time; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D000069552:Rivaroxaban / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; C025667:prothrombin complex concentrates; C522181:apixaban; D000069552:Rivaroxaban; C552171:edoxaban
keywords: antifactor Xa activity; apixaban; edoxaban; prothrombin time; rivaroxaban