title: Evaluation of Factor Xa-Specific Chromogenic Substrate Assays and the Determination of Pharmacokinetics of Fondaparinux.
abstract: Fondaparinux (FPX), a synthesized factor Xa inhibitor, is one of the most popular anticoagulants for the prevention of postoperative venous thromboembolism (VTE). Although routine monitoring is not required, the bleeding adverse events cannot be neglected, and the measurement of anti-Xa activity is expected to be monitored. The primary purpose of this study is to evaluate the performances of 2 chromogenic assays for the detection of anti-Xa activity. Furthermore, the pharmacokinetics of FPX was examined using chromogenic assays. Anti-Xa activity was measured using 2 FPX-based chromogenic substrates (S2222 and STA-Liquid Anti-Xa). The reproducibility, detection limits, linearity, and correlations between the substrates were examined using normal plasma doped with low and high concentrations of FPX formulation. In addition, anti-Xa activity in 235 clinical samples from 164 cases treated was measured, and the pharmacokinetics of FPX was evaluated. Both of the tested substrates were capable of accurately measuring the anti-Xa activity of FPX, with a lower limit of 0.05 μg/mL and a coefficient of variation of less than 10%. The repeated administration of FPX induced a gradual but significant increase in the anti-Xa activity, which was negatively correlated with body weight and estimated glomerular filtration rate. No significant correlation between the anti-Xa activity and the occurrence of postoperative VTE or bleeding event was observed. Anti-Xa activity can be successfully determined using 2 chromogenic assays and automated biochemical analyzers. The clinical significance of anti-Xa activity monitoring should be examined in the future study.
authors.affiliation: Division of Clinical Laboratory, Juntendo University Hospital, Bunkyo-ku, Tokyo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Yuri
authors.affiliation: Department of Clinical Laboratory Medicine, Juntendo University School Medicine, Bunkyo-ku, Tokyo, Japan tabe@juntendo.ac.jp.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tabe
authors.affiliation: Division of Clinical Laboratory, Juntendo University Hospital, Bunkyo-ku, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Department of Orthopaedics, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sadatsuki
authors.affiliation: Department of Coloproctological Surgery, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Aoki
authors.affiliation: Division of Clinical Laboratory, Juntendo University Hospital, Bunkyo-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Horii
authors.affiliation: Department of Emergency and Disaster Medicine, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Iba
authors.affiliation: Division of Clinical Laboratory, Juntendo University Hospital, Bunkyo-ku, Tokyo, Japan.
authors.forename: Akimichi
authors.initials: A
authors.lastname: Ohsaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000493:pharmacokinetics; D001835:Body Weight; D002863:Chromogenic Compounds; D019963:Clinical Chemistry Tests / Q000379:methods / Q000592:standards*; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000493:pharmacokinetics; D005260:Female; D000077425:Fondaparinux; D005919:Glomerular Filtration Rate; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011183:Postoperative Complications / Q000517:prevention & control; D054556:Venous Thromboembolism / Q000517:prevention & control
chemical_list: D000925:Anticoagulants; D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D011134:Polysaccharides; D000077425:Fondaparinux
keywords: chromogenic substrate assay; factor Xa inhibitor; fondaparinux