Impact Factor 3.845 | CiteScore 3.92
More on impact ›

Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.01177

International normalized ratio as a screening test for assessment of anticoagulant activity for patients treated with rivaroxaban or apixaban: A pilot study

 Fanny Ofek1, 2*,  Dana Barchel3, Ahmad Mahajna3, Talia Filipovich-Rimon4, Osnat Garach-Jehoshua4, Maya Berlin5, Matitiahu Berkovitch6,  Nofar Perets7 and  Tomer Ziv-Baran8
  • 1Sackler School of Medicine, Tel-Aviv University, Tel-Aviv., Assaf Harofeh Medical Center, Israel
  • 2Other, Israel
  • 3Department of Internal Medicine, Assaf Harofeh Medical Center, Israel
  • 4Department of Hematology, Sackler School of Medicine, Sackler Faculty of Medicine, Tel Aviv University, Israel
  • 5Unit for Clinical Pharmacology and Toxicology, Assaf Harofeh Medical Center, Israel
  • 6Assaf Harofeh Medical Center, Israel
  • 7Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem., Israel
  • 8Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler School of Medicine, Tel-Aviv University, Israel

In patients treated with direct oral anti activated factor X (anti-FXa) anticoagulants such as apixaban and rivaroxaban, there are several emergency and non-emergency conditions in which anticoagulation activity should be measured. The validity of the common global clotting tests, Prothrombin time and International Normalized Ratio (PT/INR) for determination of blood levels of these drugs has been widely investigated. As the anticoagulation activity evaluation "calibrated anti-FXa" of these drugs, is relatively more expensive and less available, we aimed to build a prediction model for anticoagulation activity assessment based on INR values.

Methods and findings
160 samples from 80 hospitalized patients treated with apixaban or rivaroxaban, were tested using PT/INR, and Anti-FXa chromogenic assay. Two blood samples, trough and peak, were collected from each subject. Participants were randomly divided into two equal groups. One group (n=40) was used to build the model, which was validated by the second group (n=40). There was a strong correlation between anti-FXa concentrations and INR in rivaroxaban treated patients (r = 0.899, p<0.001). Therefore, we were able to build a formula for rivaroxaban patient group which reliably represent the relationship between these two parameters. The correlation in apixaban treated patients was less predictive (r = 0.798, p<0.001) and the formula suggested could not be validated.

In our study, we developed a formula that estimates the anticoagulant activity of rivaroxaban by obtaining INR values. Where anti-FXa assay is unavailable our proposed formula may be considered as a screening test for rivaroxaban.

Keywords: rivaroxaban, apixaban, INR, anti-FXa activity, Direct oral anti- FXa anticoagulants, Anti-FXa chromogenic assay.

Received: 26 Jun 2019; Accepted: 13 Sep 2019.

Copyright: © 2019 Ofek, Barchel, Mahajna, Filipovich-Rimon, Garach-Jehoshua, Berlin, Berkovitch, Perets and Ziv-Baran. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Fanny Ofek, Assaf Harofeh Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv., Tel Aviv, Israel,