COMMENTARY

Does atrial fibrillation confer a hypercoagulable state?

Acute ischemic stroke (AIS) is the most common type of stroke and requires immediate reperfusion. Current acute reperfusion therapies comprise the administration of intravenous thrombolysis and/or endovascular thrombectomy. Although these acute reperfusion therapies are increasingly successful, optimized secondary antithrombotic treatment remains warranted, specifically to reduce the risk of major bleeding complications. In the development of AIS, coagulation and platelet activation play crucial roles by driving occlusive clot formation. Recent studies implicated that the intrinsic route of coagulation plays a more prominent role in this development, however, this is not fully understood yet. Next to the acute treatments, antithrombotic therapy, consisting of anticoagulants and/or antiplatelet therapy, is successfully used for primary and secondary prevention of AIS but at the cost of increased bleeding complications. Therefore, better understanding the interplay between the different pathways involved in the pathophysiology of AIS might provide new insights that could lead to novel treatment strategies. This narrative review focuses on the processes of platelet activation and coagulation in AIS, and the most common antithrombotic agents in primary and secondary prevention of AIS. Furthermore, we provide an overview of promising novel antithrombotic agents that could be used to improve in both acute treatment and stroke prevention.

Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti‐inflammatory and cardiovascular‐protective effects besides its well‐established anticoagulant properties; however, these remain poorly characterized. Extracellular vesicles (EVs) are important circulating messengers regulating a myriad of biological and pathological processes and may be highly relevant to the pathophysiology of atrial fibrillation as they reflect alterations in platelet and endothelial biology. However, the effects of rivaroxaban on circulating pro‐inflammatory EVs remain unknown.

We hypothesized that rivaroxaban’s anti‐inflammatory properties are reflected upon differential molecular profiles of circulating EVs.

Differences in circulating EV profiles were assessed using a combination of single vesicle analysis by Nanoparticle Tracking Analysis and flow cytometry, and proteomics.

We demonstrate, for the first time, that rivaroxaban‐treated non‐valvular atrial fibrillation (NVAF) patients (n=8) exhibit attenuated inflammation compared with matched warfarin controls (n=15). Circulating EV profiles were fundamentally altered. Moreover, quantitative proteomic analysis of enriched plasma EVs from six pooled biological donors per treatment group revealed a profound decrease in highly pro‐inflammatory protein expression and complement factors, together with increased expression of negative regulators of inflammatory pathways. Crucially, a reduction in circulating levels of soluble P‐selectin was observed in rivaroxaban‐treated patients (compared with warfarin controls), which negatively correlated with the patient’s time on treatment.

Collectively, these data demonstrate that NVAF patients anticoagulated with rivaroxaban (compared with warfarin) exhibit both a reduced pro‐inflammatory state and evidence of reduced endothelial activation. These findings are of translational relevance toward characterizing the anti‐inflammatory and cardiovascular‐protective mechanisms associated with rivaroxaban therapy.

The purpose of this study is to investigate the incidence and timing of postoperative, symptomatic pulmonary embolism (PE) in patients receiving nonwarfarin treatment following primary total joint arthroplasty (TJA), to clarify the appropriate duration of postoperative VTE prophylaxis.

We retrospectively reviewed the medical records of 11,148 patients who underwent primary TJA, including total knee arthroplasty and total hip arthroplasty at our institution between January 2012 and March 2019. The median postoperative day of diagnosis of symptomatic PE and the interquartile range for day of diagnosis were determined. Multivariate Cox proportional hazards modeling was used to test the difference of timing for PE based on demographics and comorbidities.

The overall 90-day rate of symptomatic PE was 0.71%. The median day of diagnosis for symptomatic PE was 3 days postoperatively (interquartile range, 2-7 days). Factors showed statistical significance on multivariate analysis in association with earlier timing of PE occurrence in patients with atrial fibrillation, diabetes mellitus, coronary heart disease, and history of stroke.

The vast majority of symptomatic PE occurs in the early postoperative period after TJA, and atrial fibrillation, diabetes mellitus, coronary heart disease, and history of stroke were independent factors affecting the timing of symptomatic PE.