ORIGINAL ARTICLESEffects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillationPetkovic, Anicaa,b; Al-Khalili, Farisc; Antovic, Aleksandrad; Ammar, Majeede,f,g; Pruner, Ivab,h; Vranic, Aleksandraa; Soutari, Nidab,i; Zdravkovic, Nebojsaj; Malmström, Rickard E.k; Jakovljevic, Vladimirl,m; Antovic, Jovan P.b,iAuthor Information aDepartment of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia bDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden cDepartment of Clinical Sciences, Danderyds Hospital, Karolinska Insitutet, Stockholm, Sweden dDivision of Rheumatology, Department of Medicine, Karolinska Institutet and Academic Specialist Center, Center for Rheumatology, Stockholm Health Services, Stockholm, Sweden eCentral Clinical School, Monash University fDepartment of Gastroenterology, The Alfred, Melbourne, Victoria, Australia gDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden hInstitute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia iClinical Chemistry, Karolinska University Hospital, Stockholm, Sweden jDepartment of Medical Statistics and Informatics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia kDepartment of Medicine Solna, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden lDepartment of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia mDepartment of Human Pathology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia Correspondence to Anica Petkovic, MPharm, Teaching Assistant, Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac Svetozara Markovica 69, Kragujevac 34000, Serbia; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden Tel: +381 306 800/+381 66 315 255; fax: +381 306 800x112; e-mail: firstname.lastname@example.org Received 11 November, 2019 Revised 25 January, 2020 Accepted 18 February, 2020 Blood Coagulation & Fibrinolysis: June 2020 - Volume 31 - Issue 4 - p 243-252 doi: 10.1097/MBC.0000000000000907 Buy Metrics Abstract The study was aimed to evaluate the effects of two standard doses of rivaroxaban and dabigatran on global hemostatic assays in patients with atrial fibrillation. The study included 52 patients treated with rivaroxaban (15/20 mg), 50 on dabigatran (110/150 mg) and 20 healthy individuals. Platelet-poor plasma was used for determination of three global hemostatic assays, namely endogenous thrombin potential (ETP), calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP). Rivaroxaban and dabigatran reduced ETP (P < 0.01) although OHP (P < 0.05) was diminished only by dabigatran. Strong correlations were noticed between ETP parameters and the plasma concentrations of rivaroxaban (ETP, r = −0.51; c-max, r = −0.85; t-lag, r = 0.83; t-max, r = 0.66) as well as with plasma concentration of dabigatran (ETP, r = −0.75; c-max, r = −0.74; t-lag, r = 0.73; t-max, r = 0.52). Analysis of dabigatran concentrations under 50 ng/ml showed that ETP parameter has area under the concentration–time curve-receiver operating characteristic value of 0.879 (95% confidence interval 0.776–0.980). Dabigatran treatment paradoxically increased area under the concentration–time curve and peak values although rivaroxaban decreased peak values (P < 0.01). However, significant correlation between CAT parameters and plasma concentration of both direct oral anticoagulants was not observed. We confirmed that the CAT assay is inappropriate for estimation of dabigatran effects and is not fully sensitive as regards rivaroxaban. The ETP assay can potentially be the appropriate method for estimation of global hemostatic capacity as regards both direct oral anticoagulants. The role of OHP needs to be confirmed in additional studies. ETP parameter of chromogenic assay has promising potential in exclusion of high plasma concentrations of dabigatran. Copyright © 2020 YEAR Wolters Kluwer Health, Inc. All rights reserved.