title: Ex vivo  effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions.
abstract: Global coagulation assays display variable effects at different concentrations of rivaroxaban. The aim of this study is to quantify the  ex vivo  effects of low-dose rivaroxaban on thrombophilia screening assays and coagulation factor activities  based on the administration time, and to show how to mask possible interferences. Plasma samples from 40 patients receiving rivaroxaban 10 mg daily were investigated to measure activities of clotting factor II, V, VII, VIII, IX, XI, XII and XIII; protein C- and protein S-levels; lupus anticoagulants; anticardiolipin IgG and IgM; D-dimer, heparin-platelet factor 4 (HPF4) antibodies and screening tests for von Willebrand disease (VWD). Two hours after  rivaroxaban administration, the activities of clotting factors were significantly decreased to different extents, except for factor XIII. Dilution of plasma samples resulted in neutralisation of these interferences. The chromogenic protein C activity assay was not affected by rivaroxaban. Depending on the timing of tablet intake in relation to blood sampling protein S activity was measured falsely high when a clotting assay was used. False-positive results for lupus anticoagulants were observed depending on the assay system used and the administration time of rivaroxaban. ELISA-based assays such as anticardiolipin IgG and IgM, D-dimer, HPF4-antibodies and the turbidimetric assays for VWD were not affected by rivaroxaban. Specific haemostasis clotting tests should be performed directly prior to rivaroxaban intake. Assay optimisation in the presence of rivaroxaban can be achieved by plasma dilution. Immunologic assays are not influenced by rivaroxaban, while chromogenic assays can be used, when they do not depend on factor Xa.
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine, Johann Wolfgang Goethe-University Hospital Frankfurt/Main, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Helen.Mani@kgu.de
authors.forename: Helen
authors.initials: H
authors.lastname: Mani
authors.forename: Christian
authors.initials: C
authors.lastname: Hesse
authors.forename: Gertrud
authors.initials: G
authors.lastname: Stratmann
authors.forename: Edelgard
authors.initials: E
authors.lastname: Lindhoff-Last
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001780:Blood Coagulation Tests / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D002863:Chromogenic Compounds; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005189:False Positive Reactions; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage*; D009391:Nephelometry and Turbidimetry; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D000069552:Rivaroxaban; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013876:Thiophenes / Q000008:administration & dosage*; D019851:Thrombophilia / Q000097:blood / Q000175:diagnosis*; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D001779:Blood Coagulation Factors; D002863:Chromogenic Compounds; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013607:Tablets; D013876:Thiophenes; D000069552:Rivaroxaban; D015951:Factor Xa