Downloaded from http://journals.lww.com/drug-monitoring by BhDMf5ePHKbH4TTImqenVIdHfOa5cT8d0MW97pzEYFJXaKqSbNykfxCZ/aSXqfWMZLhxYpeNRuc= on 10/07/2020 ORIGINAL ARTICLE Perils of Antithrombotic Transitions: Effect of Oral Factor Xa Inhibitors on the Heparin Antifactor Xa Assay Tania Ahuja, PharmD, AACC, BCCP, BCPS, CACP, Irene Yang, PharmD, Quy Huynh, PharmD, BCPS, John Papadopoulos, BS, PharmD, FCCM, BCCCP, and David Green, MD, PhD Background: Oral factor Xa inhibitors (OFXais) may interfere with the heparin antifactor Xa (antiXa) assay. The best method to measure heparin activity during the transition from an OFXai to intravenous (IV) unfractionated heparin (UFH) remains unknown. This study aimed to assess the safety and effectiveness of transitioning from an OFXai to UFH. Methods: A retrospective analysis was conducted of patients with supratherapeutic antiXa levels on UFH who received either apixaban or rivaroxaban within 72 hours before UFH initiation at NYU Langone Health. The primary objective was to identify the incidence of interference on the heparin antiXa assay due to OFXai exposure in the previous 72 hours. The secondary outcomes included the indication for transition to UFH and the rate of thromboembolic and bleeding events. Results: A total of 93 patients with supratherapeutic antiXa activity levels with prior OFXai use were reviewed. Moderate renal impairment, defined as creatinine clearance less than 49 mL/min, was present in 67 (72%) patients. The primary indication for transition from OFXai to UFH was in anticipation for a procedure, and it occurred in 37 (40%) patients. There were 3 major bleeding events and 3 clinically relevant nonmajor bleeding events. No thromboembolic events occurred. Conclusions: This study assessed the prevalence of suprathera- peutic antiXa levels and clinical outcomes during the transition from OFXais to UFH. Health care systems should develop guidelines to assist clinicians in monitoring antiXa activity in patients undergoing a transition from an OFXai to UFH. It is also important to assess the patient’s underlying thromboembolic and bleeding risks. Key Words: anticoagulants, factor Xa inhibitors, unfractionated heparin, transition, antiXa (Ther Drug Monit 2020;42:737–743) INTRODUCTION Unfractionated heparin (UFH) was discovered in 1916 and first used clinically in 1937; however, the optimal coagulation laboratory assay to monitor the safety and effectiveness of heparin remains unknown. 1 The activated partial thromboplastin time (aPTT) is often used as a global test to reflect the ability of the heparin–antithrombin complex to inactivate thrombin and factor Xa. Given the variations in reagents and recommendations from the American College of Chest Physicians and the College of American Pathologists, aPTT tests should be calibrated annually, or a more specific heparin assay, such as the antiXa heparin activity test, should be used to monitor a safe therapeutic range. 1 Unlike aPTT, the antiXa heparin assay is not affected by coagulation factors, such as factor VIII or IX deficiency, underlying thrombo- philia, lupus anticoagulants, or liver diseases. 2 In one single- center, prospective, cohort pilot study of 85 patients, moni- toring of heparin concentrations using an antiXa assay re- sulted in a therapeutic range more frequently than that using an aPTT-based assay. 3 An antiXa-based protocol also ach- ieved therapeutic values sooner and showed no difference in the rates of thrombosis or bleeding compared with an aPTT-based protocol. 3 In 2012, NYU Langone Health (NYULH) transitioned from an aPTT assay to an antiXa heparin assay for monitoring UFH. At NYULH, UFH is monitored, and doses are adjusted by a nurse-driven titration protocol. The initial bolus and continuous infusion dose, goal antiXa activity, and titration parameters vary based on the indication for UFH. The protocol at NYULH considers antiXa activity levels between 0.3 and 0.7 IU/mL to be therapeutic for venous clots, and levels between 0.3 and 0.5 IU/mL for arterial indications, with subtherapeutic levels below 0.3 IU/mL and supratherapeutic levels above 0.7 IU/ mL. AntiXa activity levels greater than 0.9 IU/mL are con- sidered critical, requiring temporary holding of UFH, further monitoring, and subsequent dose reduction. The antithrombotic therapy team oversight group (ATTOG) at the NYULH monitors compliance to the UFH protocol by assessing the time in therapeutic range for antiXa activity levels of 0.3–0.7 IU/mL. In 2017, there was an Received for publication November 25, 2019; accepted April 28, 2020. From the Department of Pharmacy, NYU Langone Health, New York, NY. T. Ahuja designed the research, interpreted the data, and provided vital review and oversight of the research and the manuscript. I. Yang performed the research, analyzed and interpreted the data, and wrote the first draft of the manuscript. Q. Huynh interpreted the data and reviewed the manuscript. D. Green and J. Papadopoulos provided vital review of the manuscript. All authors were responsible for and approved the final version of the manuscript. The authors declare no conflict of interest. Contents of this manuscript have been presented in the form of a poster at the American Society of Health-System Pharmacists (ASHP) 2018 Midyear Clinical Meeting, Anaheim, CA. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Correspondence: Tania Ahuja, PharmD, AACC, BCCP, BCPS, CACP, Department of Pharmacy, NYU Langone Health, 550 First Avenue, New York, NY 10016 (e-mail: Tania.Ahuja@nyulangone.org). Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. Ther Drug Monit  Volume 42, Number 5, October 2020 737 Copyright © 2020 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.