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.

Key Words::

• Arachidonic acid
• ADP
• circadian rhythm
• platelet aggregation
• ristocetin
• rivaroxaban
• TRAP peptide
• von Willebrand Factor
• factor Xa

Acknowledgements

The study was supported by the Bürgermeisterfonds of the city Vienna. C.S. and M.S. were supported by the FWF (Fonds zur Förderung der wissenschaftlichen Forschung), grant number 14005. The authors would like to thank the laboratory technicians Christa Drucker and Karin Petroczi for technical assistance and study nurse Edith Lackner for her contribution to the conduct of the study.

Declaration of interest: Bernd Jilma has been acting as the principal investigator of several studies sponsored by Bayer AG. The authors report no other conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Appendix Figure I to be found online at http://informahealthcare.com/doi/abs/10.3109/00365513.2015.1057896.