title: Assessing the influence of diurnal variations and selective Xa inhibition on whole blood aggregometry.
abstract: A biological rhythm in platelet function is well known. Multiple electrode aggregometry (MEA) is a widely used assay to measure platelet aggregability. Rivaroxaban is a new oral anticoagulant frequently used in an increasing number of indications. In this randomized, crossover trial we investigated whether a biological rhythm exists in MEA measurements and potential effects of rivaroxaban on platelet aggregation. Sixteen healthy volunteers were included in the study and blood samples were obtained at 08:00, 12:00, 16:00 and 20:00 h. Each subject was tested without rivaroxaban intake first and randomly assigned to 3 days of rivaroxaban intake at 08:00 or 3 days of rivaroxaban intake at 20:00 h and vice versa. In MEA measurements, a significant increase in platelet aggregation after addition of ristocetin at 12:00 h compared to other investigated time-points (122 ± 8 AU at 12:00 h vs. 109 ± 9 AU at 08:00 h, 114 ± 10 AU at 16:00 h and 103 ± 8 AU at 20:00 h, p = 0.027) could be detected. There was no biological rhythm detectable using other agonists (ADP, arachidonic acid, thrombin-receptor activating peptide-6). After rivaroxaban intake at 08:00 h an increased ristocetin-induced platelet aggregation was measured in the next morning (126 ± 4 AU (rivaroxaban at 08:00 h) vs. 109 ± 9 AU (no rivaroxaban), 111 ± 6 AU (rivaroxaban at 20:00 h; p = 0.002). No other effects of rivaroxaban on platelet function were found. We detected a biological rhythm in ristocetin-induced platelet aggregation with a peak at 12:00 h (noon). No influence of selective Xa inhibition on platelet aggregation was detected.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna , Vienna , Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Schoergenhofer
authors.forename: Michael
authors.initials: M
authors.lastname: Schwameis
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Felix
authors.initials: F
authors.lastname: Winkler
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.forename: Sophie
authors.initials: S
authors.lastname: Brunner-Ziegler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D015951:Factor Xa / Q000032:analysis; D065427:Factor Xa Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests / Q000379:methods; D000069552:Rivaroxaban / Q000494:pharmacology*; D055815:Young Adult; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D065427:Factor Xa Inhibitors; D014841:von Willebrand Factor; D000069552:Rivaroxaban; D015951:Factor Xa
keywords: ADP; Arachidonic acid; TRAP peptide; circadian rhythm; factor Xa; platelet aggregation; ristocetin; rivaroxaban; von Willebrand Factor