Division of Cardiology, Department of Cardiothoracic and Respiratory Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy.
Department of Cardiology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark.
Semin Thromb Hemost. 2018 Apr;44(3):249-260. doi: 10.1055/s-0037-1605564. Epub 2017 Sep 12.
Venous thromboembolism (VTE) is a frequent cause of disability and mortality worldwide. Von Willebrand factor (VWF) is a major determinant of hemostasis and clot formation, in both arteries and veins. Although VWF is mainly known for its role in arterial thrombosis, several studies suggest a pathogenic role for VWF and its regulator ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) in venous thrombosis. Nongenetic and genetic factors, including gene mutations and polymorphisms, aging, hormone status, ABO blood groups, and systemic inflammation, have been involved in the modulation of both VTE predisposition and plasma levels of VWF. In several clinical settings, including inflammatory disease and cancer, VWF and ADAMTS-13 are currently investigated as possible determinants of vein thrombosis. These data indicate VWF as a potential therapeutic target in the management of VTE. Several studies report unselective antagonism of VWF for drugs used in daily clinical practice, including heparin and statins. Selective inhibition of VWF pathway has recently been tested in animal models of arterial and venous thrombosis as a novel therapeutic strategy to prevent platelet aggregation and thrombosis, promote vein lumen recanalization, and improve vein valve competency with excellent safety profile. In this review, we summarize the role of VWF in VTE, focusing on clinical and potential therapeutic implications.
静脉血栓栓塞症（VTE）是全球范围内导致残疾和死亡的常见原因。血管性血友病因子（VWF）是止血和血栓形成的主要决定因素，无论是在动脉还是静脉中。尽管 VWF 主要因其在动脉血栓形成中的作用而为人所知，但有几项研究表明 VWF 及其调节剂 ADAMTS-13（一种带有血小板反应蛋白 1 型基序的解整合素金属蛋白酶 13）在静脉血栓形成中具有致病作用。非遗传和遗传因素，包括基因突变和多态性、衰老、激素状态、ABO 血型和全身炎症，都参与了 VTE 易感性和 VWF 血浆水平的调节。在包括炎症性疾病和癌症在内的几种临床情况下，VWF 和 ADAMTS-13 目前被作为静脉血栓形成的可能决定因素进行研究。这些数据表明 VWF 是管理 VTE 的潜在治疗靶点。几项研究报告称，在日常临床实践中使用的药物（包括肝素和他汀类药物）对 VWF 进行非选择性拮抗。最近，在动脉和静脉血栓形成的动物模型中测试了 VWF 途径的选择性抑制，作为一种预防血小板聚集和血栓形成、促进静脉腔再通以及改善静脉瓣功能的新型治疗策略，具有极好的安全性。在这篇综述中，我们总结了 VWF 在 VTE 中的作用，重点关注临床和潜在的治疗意义。
