title: Anti-coagulation assessment with prothrombin time and anti-Xa assays in real-world patients on treatment with rivaroxaban.
abstract: Monitoring of anti-coagulation with the direct factor Xa inhibitor rivaroxaban is considered unnecessary in a routine clinical setting. However, assessment of its anti-coagulant effect may be desirable in certain clinical situations. We assessed prothrombin time (PT) reagents and commercially available anti-Xa assays (Biophen) calibrated for rivaroxaban and heparin in comparison to liquid chromatography-mass spectrometry (LC-MS/MS) measurements of rivaroxaban concentration in samples from patients on treatment with rivaroxaban for stroke prevention in atrial fibrillation. Citrate plasma samples were obtained from 30 randomly selected patients on uninterrupted treatment with rivaroxaban for a minimum of 1 month. The anti-Xa assays, direct Xa inhibitor (DiXa-I®), and Heparin LRT® were conducted for both wide and low calibrations for rivaroxaban. Measurements were compared to LC-MS/MS using correlation, linear regression, intra-class correlation, and Bland-Altman analysis. In 30 patients (9 female) of median age 71.5 years and BMI 26.5 kg/m(2), rivaroxaban concentrations between 2.4 and 625 ng/ml (median 82 ng/ml) were measured by LC-MS/MS. PT reagents were poorly correlated with rivaroxaban concentrations (r (2) = 0.52 and 0.09). Anti-Xa assays DiXa-I (r (2) = 0.95) and Heparin LRT (r (2) = 0.97) were correlated with rivaroxaban in all concentrations, but especially in low concentrations with low calibrations (r (2) = 0.97 and 0.98, respectively). The highest agreement occurred between Heparin LRT and low rivaroxaban concentrations with a mean difference of -5.3 ng/ml (limits of agreement, 12.9 to 2.4 ng/ml). Anti-Xa assays can indirectly determine the concentration of rivaroxaban for a wide range of concentrations in real-world patients. An interpretation of anti-Xa and PT measurements in treatment with rivaroxaban requires knowledge of the local reagents.
authors.affiliation: Clinical Division of Hematology and Hemostaseology, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Königsbrügge
authors.forename: Peter
authors.initials: P
authors.lastname: Quehenberger
authors.forename: Sabine
authors.initials: S
authors.lastname: Belik
authors.forename: Günter
authors.initials: G
authors.lastname: Weigel
authors.forename: Christoph
authors.initials: C
authors.lastname: Seger
authors.forename: Andrea
authors.initials: A
authors.lastname: Griesmacher
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
authors.forename: Cihan
authors.initials: C
authors.lastname: Ay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000097:blood / Q000517:prevention & control; D015951:Factor Xa / Q000032:analysis / Q000378:metabolism*; D065427:Factor Xa Inhibitors / Q000008:administration & dosage*; D005260:Female; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D009025:Morpholines / Q000008:administration & dosage*; D011517:Prothrombin Time; D000069552:Rivaroxaban; D020521:Stroke / Q000097:blood / Q000517:prevention & control; D013876:Thiophenes / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D006493:Heparin; D000069552:Rivaroxaban; D015951:Factor Xa