The impact of rivaroxaban on primary hemostasis in patients with venous thrombosis

Abstract

Factor Xa inhibitors are safe and effective alternatives to warfarin, but several studies indicate that rivaroxaban may cause a different risk profile for bleeding. For instance, while the risk of major bleeding in general may be lower with rivaroxaban than for warfarin, the risk of gastrointestinal bleeding or abnormal uterine bleeding may be higher. The underlying mechanisms for these differences are not known, and the effect of rivaroxaban on primary hemostasis is poorly understood. The aim of this study was to investigate the effect of rivaroxaban on platelet function, P-selectin and von Willebrand factor (VWF) antigen and activity. Patients with venous thrombosis assigned to 3 months of treatment due to temporary risk factors were included. Blood was collected both during (on-treatment) and 4–6 weeks after end of treatment (without treatment). The platelet reactivity was assessed by light transmission aggregometry. P-selectin was measured by an enzyme-linked immunosorbent assay and vWF antigen and activity by latex immunoagglutination assays. Platelet reactivity during on-treatment (trough- and peak concentration) was similar to values without treatment. There was a trend toward a reduction of P-selectin during rivaroxaban treatment (peak concentration) compared to value without treatment (p = 0.06). There were no differences in vWF antigen and activity between the different time-points. We found no difference in platelet reactivity or vWF antigen/activity during rivaroxaban treatment compared with values without treatment. Apart from possibly causing a reduction of P-selectin, rivaroxaban seems not to influence primary hemostasis.

Keywords:

• Platelet aggregation
• P-selectin
• rivaroxaban
• von Willebrand factor

Acknowledgements

We are grateful to Marie Skogstad Le at the department of Medical Biochemistry, Oslo University Hospital for performing the VWF measurements, and Jeanette Konstanse Steen and Ingebjørg Seljeflot at the Center for Clinical Heart Research, Oslo University Hospital for performing the P-selectin measurements. We are also grateful for the statistical support provided by Lien My Diep at Oslo Centre for Biostatistics and Epidemiology (OCBE), Oslo University Hospital.

Declaration of interest

The study was financially supported by an unrestricted research grant from Bayer, Germany.

Statement of Contribution

N.H. Schultz has conducted the laboratory work and written the manuscript. P.A. Holme has designed and planned the study, analyzed the results and contributed to the manuscript. S. Bjørnsen has performed the platelet aggregation. C.E. Henriksson, PM Sandset and E.M. Jacobsen have planned the study, analyzed the results and contributed to the manuscript.