The effect of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers

Abstract

The new oral anticoagulants (NOACs) reduce stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF), but dabigatran may increase risk of coronary ischemic events for unclear reasons. Thus, this study assessed the effects of dabigatran and rivaroxaban on platelet reactivity and inflammatory markers in patients with non-valvular AF. Patients with non-valvular AF planned to begin treatment with NOACs were included. Seventeen patients were prescribed dabigatran and ten rivaroxaban. Platelet function (as assessed by multiple-electrode aggregometry, Impact-R shear-induced platelet deposition, P-selectin expression and plasma RANTES levels) and high-sensitivity C-reactive protein (hs-CRP) were measured at enrollment (prior to initiation of NOAC treatment) and at least 7 days into treatment with either dabigratran or rivaroxaban. Seventeen patients treated with dabigatran (mean age 69 ± 7 years, 35 % women, mean CHADS2 score 2.6 ± 1.2), and ten patients treated with rivaroxaban (mean age 73 ± 9 years, 20 % women, mean CHADS2 score 2.7 ± 1.6) completed the study. In both groups, there were no significant differences in platelet reactivity between the baseline and on-anticoagulant treatment time-points, as measured by each of the platelet-specific assays. There was a trend towards increased platelet reactivity in response to arachidonic acid from baseline to on-treatment in both groups, probably as a result of aspirin discontinuation in 33 % of patients. No significant differences were noted between baseline and on-treatment in hs-CRP in both anticoagulant groups. Treatment with dabigatran and rivaroxaban does not appear to be associated with changes in markers of platelet reactivity or systemic inflammation.

Effect of the FXa inhibitors Rivaroxaban and Apixaban on platelet activation in patients with atrial fibrillation

“…Our data are in line with a report of Zemer-Wassercug et al who also failed to demonstrate any significant changes in platelet reactivity measured by multiplate-aggregation, platelet P-Selectin expression and plasma RANTES levels from baseline to at least 7 days on Rivaroxaban or dabigatran therapy [18]. Since the average life span of circulating platelets is 8-9 days, effects on megakaryocytes and mRNA derived platelet protein synthesis in response to cellular activation might have been missed in this study.…”

Inhibitory mechanisms of very low–dose rivaroxaban in non–ST-elevation myocardial infarction

“…32,33 HMGB-1 is highly expressed in platelet-rich human coronary artery thrombi 34 and a key mediator of reciprocal communication between platelet and neutrophils, as well as monocytes facilitating formation of prothrombotic neutrophil extracellular traps and production of monocyte-derived tissue factor. 33 We found that P-selectin exposure was not affected by VLD rivaroxaban treatment, findings that are in line with previous studies 35,36 that both found no significant effect of rivaroxaban on platelet P-selectin expression and release. However, in the present study, we could show that platelet surface abundance of HMGB-1 was significantly reduced after treatment with VLD rivaroxaban pointing to a potential effect on thrombo-inflammatory processes triggered by platelets in patients with coronary artery disease.…”

Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer

“…Quercetin does not affect P-gp-mediated efflux, as reflected by a lack of effect on digoxin pharmacokinetics (39). We observed that isoquercetin significantly lowers soluble P selectin levels and that this is an activity not shared by other anticoagulants, such as warfarin, dabigatran, or rivaroxaban (40)(41)(42). P selectin binds to P selectin glycoprotein ligand-1 on the surface of leukocytes to promote the generation of tissue factor bearing microparticles and thrombus formation (43).…”