Department of Clinical Biochemistry, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark; Aalborg AF Study Group, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark; EVsearch.dk, Denmark.
Department of Cardiothoracic Surgery, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Søndre Skovvej 15, 9000 Aalborg, Denmark; Aalborg AF Study Group, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark.
Thromb Res. 2019 Jan;173:141-150. doi: 10.1016/j.thromres.2018.11.026. Epub 2018 Dec 2.
The risk of thrombus formation in the left atrial appendage (LAA) in patients with atrial fibrillation (AF) may result from blood stasis, local endocardial changes, and/or changed blood composition. Extracellular vesicles (EVs), especially subtypes exposing tissue factor (TF), have procoagulant capacity. We hypothesized that blood concentrations of TF-bearing EVs and other procoagulant biomarkers are elevated in AF patients, particularly in the LAA lumen.
From 13 AF patients and 12 controls a venous blood sample was drawn prior to cardiac surgery. Intraoperatively, venous blood and blood directly from the LAA was drawn. Plasma levels of EVs, including TF- and cell type specific antigen-bearing EVs, were measured using a protein microarray platform. Plasma levels of TF, von Willebrand factor (vWF), cell free deoxyribonucleic acid (cf-DNA), procoagulant phospholipids (PPLs), and total submicron particles were also evaluated.
Significantly higher EV levels, including a several-fold higher median level of TF-bearing EVs were measured in AF patients compared with controls. Median concentrations of TF and vWF were approximately 40% and 30% higher, respectively, in the AF group than in the control group, while no significant differences in levels of cf-DNA, PPLs, or total submicron particles were observed. No significant differences in levels of any of the measured analytes were observed between intraoperative venous and LAA samples.
Increased plasma concentrations of TF in AF patients are accompanied and probably at least partly explained by increased levels of TF-bearing EVs, which may be mechanistically involved in increased thrombogenicity in AF patients.
房颤（AF）患者左心耳（LAA）血栓形成的风险可能源于血液淤滞、局部心内膜变化和/或血液成分改变。细胞外囊泡（EVs），尤其是暴露组织因子（TF）的亚型，具有促凝能力。我们假设 AF 患者，尤其是 LAA 管腔内的 TF 阳性 EVs 和其他促凝生物标志物的血液浓度升高。
从 13 名 AF 患者和 12 名对照者在心脏手术前抽取静脉血样。术中，从静脉和 LAA 直接抽取静脉血。使用蛋白质微阵列平台测量 EVs，包括 TF 和细胞类型特异性抗原阳性 EVs 的血浆水平。还评估了 TF、血管性血友病因子（vWF）、游离脱氧核糖核酸（cf-DNA）、促凝血磷脂（PPLs）和总亚微米颗粒的血浆水平。
与对照组相比，AF 患者的 EV 水平明显升高，包括 TF 阳性 EVs 的中位数水平高出数倍。AF 组 TF 和 vWF 的中位数浓度分别比对照组高约 40%和 30%，而 cf-DNA、PPLs 或总亚微米颗粒的水平无显著差异。术中静脉和 LAA 样本之间观察到任何测量分析物的水平均无显著差异。
AF 患者血浆中 TF 浓度升高，同时伴有并可能至少部分解释为 TF 阳性 EVs 水平升高，这可能与 AF 患者血栓形成增加的机制有关。
