Lopez-Castaneda Sandra, Valencia-Hernández Ignacio, Arean Carlos, Godínez-Hernández Daniel, Viveros-Sandoval Martha Eva
1 Laboratorio de Hemostasia y Biología Vascular, Facultad de Ciencias Médicas y Biológicas "Dr. Ignacio Chávez", Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacán, México.
2 Laboratory of Pharmacodynamics, Section of Postgraduate Studies, Escuela Superior de Medicina, Instituto Politécnico Nacional CDMX, Mexico City, Mexico.
Clin Appl Thromb Hemost. 2018 May;24(4):647-654. doi: 10.1177/1076029617711803. Epub 2017 Jun 15.
von Willebrand factor (vWF) is a multimeric glycoprotein present in blood plasma. It is synthesized in megakaryocytes and endothelial cells, secreted into circulation in the form of high-molecular-weight multimers (HMWMs), and cleaved into shorter, less active multimers by ADAMTS13. It is essential for platelet adhesion and aggregation. Previous studies have investigated the relationship between vWF levels and thromboembolic events with little regard to vWF multimeric structure. Patients with atrial fibrillation (AF) exhibit higher plasma vWF and lower ADAMTS13 levels. One hundred seven patients with AF, 51 anticoagulated and 56 nonanticoagulated, were eligible for the study. Plasma samples were analyzed for vWF antigen, vWF activity, and ADAMTS13; vWF multimers were analyzed by Western blot in 1% to 1.3% sodium dodecyl sulfate agarose gel electrophoresis. Patients with AF without oral anticoagulation (OAC) had significantly higher vWF plasma levels (154.00 [75-201] UI/dL) and vWF activity (60.00% [20%-210%]) compared to patients with OAC (133.50 [90-192] UI/dL, P = <.001; 50.00% [20%-160%], P = .02). Both were specially decreased in patients treated with acenocumarin. Patients without OAC also showed lower ADAMTS13 levels and presence of vWF HMWMs. Patients with AF show higher plasma levels and vWF activity. Moreover, treatment with traditional OAC (acenocumarin) significantly reduced vWF levels. Patients without OAC might have an increased risk of thrombotic events showing lower ADAMTS13 and higher vWF levels. Patients with stroke had higher plasma levels, vWF activity, and HMWMs. Our study suggests that increased vWF levels and presence of HMWMs could be related to cerebrovascular disease and may represent useful biomarkers for stroke in AF.
血管性血友病因子（vWF）是一种存在于血浆中的多聚体糖蛋白。它在巨核细胞和内皮细胞中合成，以高分子量多聚体（HMWMs）的形式分泌到循环系统中，并被ADAMTS13切割成较短且活性较低的多聚体。它对血小板黏附和聚集至关重要。以往的研究调查了vWF水平与血栓栓塞事件之间的关系，但很少关注vWF多聚体结构。心房颤动（AF）患者的血浆vWF水平较高，而ADAMTS13水平较低。107例AF患者符合研究条件，其中51例接受抗凝治疗，56例未接受抗凝治疗。对血浆样本进行vWF抗原、vWF活性和ADAMTS13分析；通过1%至1.3%十二烷基硫酸钠琼脂糖凝胶电泳的Western印迹法分析vWF多聚体。与接受口服抗凝药（OAC）治疗的患者相比，未接受OAC治疗的AF患者的血浆vWF水平（154.00[75 - 201]UI/dL）和vWF活性（60.00%[20% - 210%]）显著更高（接受OAC治疗的患者分别为133.50[90 - 192]UI/dL，P = <.001；50.00%[20% - 160%]，P = .02）。两者在接受醋硝香豆素治疗的患者中均特别降低。未接受OAC治疗的患者还表现出较低的ADAMTS13水平和vWF HMWMs的存在。AF患者表现出较高的血浆水平和vWF活性。此外，传统OAC（醋硝香豆素）治疗可显著降低vWF水平。未接受OAC治疗的患者可能因ADAMTS13水平较低和vWF水平较高而有增加的血栓形成事件风险。中风患者的血浆水平、vWF活性和HMWMs更高。我们的研究表明，vWF水平升高和HMWMs的存在可能与脑血管疾病有关，并且可能代表AF患者中风的有用生物标志物。
