Increased Levels of Platelets and Endothelial-Derived Microparticles in Patients With Non-Valvular Atrial Fibrillation During Rivaroxaban Therapy

Abstract

It is known that atrial fibrillation (AF) is associated with the procoagulant state. Several studies have reported an increase of circulating microparticles in AF, which may be linked to a hypercoagulable state, atrial thrombosis and thromboembolism. We evaluated in our study alterations in both platelet (PMP, CD42b) and endothelial-derived (EMP, CD144) microparticle levels on anticoagulant therapy with rivaroxaban in nonvalvular AF. After administration of rivaroxaban, PMP levels were increased (median, [IQR] 35.7 [28.8-47.3] vs. 48.4 [30.9-82.8] cells/µL; P = 0.012), along with an increase in EMP levels (14.6 [10.0-18.6] vs. 18.3 [12.9-37.1] cells/µL, P < 0.001). In the multivariable regression analysis, the independent predictor of post-dose change in PMPs was statin therapy (HR −0.43; 95% CI −0.75,−0.10, P = 0.011). The post-dose change in EMPs was also predicted by statin therapy (HR −0.34; 95% CI −0.69, −0.01, P = 0.046). This study showed an increase in both EMPs and PMPs at the peak plasma concentration of rivaroxaban. Statins have promising potential in the prevention of rivaroxaban-related PMP and EMP release. The pro-thrombotic role of PMPs and EMPs during rivaroxaban therapy requires further study.

Shape-specific microfabricated particles for biomedical applications: a review

“…Moreover, the size is critical in determining the hemocompatibility of microparticles when administered parenterally. The human body naturally produces microparticles under pathologic conditions (e.g., cancer, endothelial alterations, inflammation) [59][60][61], resulting from membrane blebbing as part of cell apoptosis [62]. Artificial microparticles (e.g., DPNs) can mitigate this risk by minimizing protein adsorption (e.g., through their materials) and by tuning the particle materials properties (i.e., particle deformability and size).…”

The dark side of foetal bovine serum in extracellular vesicle studies

“…EVs have been investigated as biomarkers in cancer because they are shed into the circulation from primary tumors (Melo et al, 2015;Zhang et al, 2017), because they can potentially be used for the early detection of metastasis (Guan et al, 2015;Saugstad et al, 2017), and because they can provide information about the disease through a easily obtained biological fluid like blood, urine, or saliva (Poulet et al, 2019). The cargo of EVs can also be used as biomarkers for neurodegenerative diseases (Hornung et al, 2020;Saugstad et al, 2017), as was demonstrated for Alzheimer's (Lee et al, 2019) and Parkinson's diseases (Russo et al, 2012), and for cardiovascular diseases (Huang et al, 2021;Lenart-Migdalska et al, 2021).…”

Extracellular Vesicles and Thrombogenicity in Atrial Fibrillation

“…The authors also noticed that the levels of circulating MVs enriched in pro-coagulant lipids (phosphatidylserine) did not significantly differ between the AF patients and healthy volunteers. On the contrary, there is a large amount of evidence regarding the fact that circulating pro-coagulant MVs were found in abundance in patients with persistent and/or permanent AF who were not receiving anticoagulant therapy compared to age-matched control subjects [76][77][78]. It is interesting to note that a number of platelet-derived MVs and endothelial cell-derived MVs were not distinguished in patients with non-valvular AF and control subjects with CV risk factors, but the total amount of EVs was significantly higher in the AF patients than it was in in healthy volunteers without known CV risk factors [76][77][78].…”

“…On the contrary, there is a large amount of evidence regarding the fact that circulating pro-coagulant MVs were found in abundance in patients with persistent and/or permanent AF who were not receiving anticoagulant therapy compared to age-matched control subjects [76][77][78]. It is interesting to note that a number of platelet-derived MVs and endothelial cell-derived MVs were not distinguished in patients with non-valvular AF and control subjects with CV risk factors, but the total amount of EVs was significantly higher in the AF patients than it was in in healthy volunteers without known CV risk factors [76][77][78]. However, the presence of AF was found to be a solid predictor of the annexin V(+) MVs level, which seems to be a marker for hypercoagulation and a risk of both atrial thrombosis and systemic thromboembolism.…”