Standard coagulation assays alone are not sufficient to exclude surgically relevant rivaroxaban plasma concentrations

Abstract

Background: While mainly larger hospitals have introduced routine anti-Xa assays for rivaroxaban (RXA), these are not readily available to smaller hospitals often relying on routine coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT).The aim of our study was to investigate the effect of RXA plasma concentration on the standard coagulation tests PT (Quick test and INR) and aPTT in a large group of real-life patients. We further assessed whether normal results of these standard coagulation assays are sufficient to exclude surgically relevant RXA plasma concentration, defined as > 50 mcg/l.; Methods: This retrospective study included all patients between 2012 and 2016 where anti-Xa (calibrated for RXA), PT (Quick test and INR), and/or aPTT were determined from the same sample. PT is expressed as Quick value (% of normal plasma pool). In total, 1027 measurements in 622 patients were eligible for analysis: 752 measurements of 505 patients for Quick/INR and 594 measurements of 417 patients for aPTT.; Results: A moderate correlation of PT/Quick (Pearson's correlation coefficient - 0.59; p < 0.001), INR (Pearson's correlation coefficient 0.5; p < 0.001), and aPTT (Pearson's correlation coefficient 0.53; p < 0.001) with RXA plasma concentration was observed. However, in 50% of all samples with a normal PT/Quick, in 25% of all samples with a normal INR and in 80% of all samples with a normal aPTT residual RXA plasma concentration was surgically relevant.; Conclusion: Although a moderate correlation of RXA plasma concentration with PT/Quick, INR, and aPTT was observed, standard coagulation assays are not sufficient to exclude surgically relevant RXA plasma concentrations.; Competing Interests: Competing interestsDS’ academic department is receiving grant support from the Swiss National Science Foundation, Berne, Switzerland, the Ministry of Health (Gesundheitsdirektion) of the Canton of Zurich, Switzerland for Highly Specialized Medicine, the Swiss Society of Anesthesiology and Reanimation (SGAR), Berne, Switzerland, the Swiss Foundation for Anesthesia Research, Zurich, Switzerland, CSL Behring, Berne, Switzerland, Vifor SA, Villars-sur-Glâne, Switzerland. DS is co-chair of the ABC-Trauma Faculty, sponsored by unrestricted educational grants from Novo Nordisk Health Care AG, Zurich, Switzerland, CSL Behring GmbH, Marburg, Germany, LFB Biomédicaments, Courtaboeuf Cedex, France and Octapharma AG, Lachen, Switzerland. DS has received honoraria or travel support for consulting or lecturing from: Danube University of Krems, Austria, US Department of Defense, WA, USA, European Society of Anesthesiology, Brussels, BE, Korea, Korean Society for Patient Blood Management, Seoul, Korea, Korean Society of Anesthesiologists, Seoul, Baxter AG, Volketswil, Switzerland, Baxter S.p.A., Roma, Italy, Bayer AG, Zürich, Switzerland, Bayer Pharma AG, Berlin, Germany, B. Braun Melsungen AG, Melsungen, Germany, Boehringer Ingelheim GmbH, Basel, Switzerland, Bristol-Myers-Squibb, Rueil-Malmaison Cedex, France and Baar, Switzerland, CSL Behring GmbH, Hattersheim am Main, Germany and Berne, Switzerland, Celgene International II Sàrl, Couvet, Switzerland, Curacyte AG, Munich, Germany, Daiichi Sankyo AG, Thalwil, Switzerland, GlaxoSmithKline GmbH & Co. KG, Hamburg, Germany, Haemonetics, Braintree, MA, USA, Instrumentation Laboratory (Werfen), Bedford, MA, USA, LFB Biomédicaments, Courtaboeuf Cedex, France, Merck Sharp & Dohme, Kenilworth, NJ, USA, Octapharma AG, Lachen, Switzerland, Organon AG, Pfäffikon/SZ, Switzerland, PAION Deutschland GmbH, Aachen, Germany, Pharmacosmos A/S, Holbaek, Denmark, Photonics Healthcare B.V., Utrecht, Netherlands, Roche Diagnostics International Ltd, Reinach, Switzerland, Roche Pharma AG, Reinach, Switzerland, Sarstedt AG & Co., Sevelen, Switzerland and Nümbrecht, Germany Schering-Plough International, Inc., Kenilworth, NJ, USA, Tem International GmbH, Munich, Germany, Verum Diagnostica GmbH, Munich, Germany, Vifor Pharma, Munich, Germany, Vienna, Austria and Villars-sur-Glâne, Switzerland, Vifor (International) AG, St. Gallen. JS received lecture honoraria and advisory honoraria from Baxter (Switzerland), Bayer (Switzerland), BMS Pfizer (Switzerland), Boehringer-Ingelheim (Switzerland), CSL Behring (Switzerland), Janssen-Cilag (Switzerland), Mitsubishi Pharma, Novo Nordisk (Switzerland), Octapharma (Switzerland), Siemens Healthineers (Switzerland). PS received honoraria for lecturing by Vifor Pharma (Munich, Germany). All other authors declare that they have no competing interests. (© The Author(s). 2019.)