title: Evaluation of a Heparin-Calibrated Antifactor Xa Assay for Measuring the Anticoagulant Effect of Oral Direct Xa Inhibitors.
abstract: The introduction of oral direct anti-Xa anticoagulants apixaban and rivaroxaban has significantly impacted the treatment and prevention of thromboembolic disease. Clinical scenarios exist in which a quantitative assessment for degree of anticoagulation due to these agents would aid management. The purpose of this work was to evaluate the chromogenic antifactor Xa assay calibrated with heparin standards at our institution for assessment of intensity of anticoagulation with rivaroxaban or apixaban in addition to its current use for unfractionated heparin or low-molecular-weight heparin. We also aimed to propose expected steady state peak and trough antifactor Xa activities for these agents based upon dosing regimens approved for nonvalvular atrial fibrillation. Antifactor Xa activity correlated very strongly with apixaban and rivaroxaban concentration in both spiked samples and treated patient plasma samples (r (2) = .99, P < .001). This correlation was observed over a broad range (20-500 ng/mL) of drug concentrations, as sample dilution with pooled normal plasma significantly extended the range of quantitative assessment. Based on drug concentrations previously published in pharmacokinetic studies, the expected steady state peak and trough antifactor Xa activity ranges for apixaban are 1.80 to 2.20 IU/mL and 0.70 to 1.10 IU/mL, respectively. For rivaroxaban, these ranges are 3.80 to 6.20 IU/mL and 0.60 to 1.00 IU/mL, respectively. In conclusion, our findings demonstrate that heparin-calibrated antifactor Xa activity correlates strongly with apixaban and rivaroxaban concentration. The dilution of samples allowed for this correlation to be extended over the majority of on-therapy drug concentrations.
authors: Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
authors: Jacob
authors: J
authors: Beyer
authors: Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
authors: Toby
authors: T
authors: Trujillo
authors: Clinical Laboratory, University of Colorado Hospital, Aurora, CO, USA.
authors: Sheila
authors: S
authors: Fisher
authors: Clinical Laboratory, University of Colorado Hospital, Aurora, CO, USA.
authors: Ann
authors: A
authors: Ko
authors: Department of Medicine and Pathology, University of Colorado School of Medicine, Aurora, CO, USA.
authors: Stuart E
authors: SE
authors: Lind
authors: Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA ty.kiser@ucdenver.edu.
authors: Tyree H
authors: TH
authors: Kiser
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000379:methods* / Q000592:standards; D002138:Calibration; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006493:Heparin / Q000592:standards; D006801:Humans; D011720:Pyrazoles / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology; D000069552:Rivaroxaban / Q000494:pharmacology; D013923:Thromboembolism / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D006493:Heparin; D000069552:Rivaroxaban
keywords: anticoagulants; clinical pharmacology; factor Xa inhibitors