POTENTIAL OF A NOVEL ANTI-PLATELET APTAMER IN OPTIMIZING ANTITHROMBOTIC

在许多临床手术中，包括经皮和外科血管重建术(PCI和CABG)、主动脉手术和其他血管干预，深入和可控的抗凝是必不可少的。各种血栓性疾病也需要立即抗凝治疗，如急性冠脉综合征、肺栓塞或深静脉血栓形成。所有这些干预和治疗的重大风险和副作用包括严重出血或血栓形成，导致脑血管或心血管损害。这些结果的临床和财务影响可能是深远的，并与延长住院时间、降低生活质量和增加卫生保健资源有关 利用率。这项拟议的工作扩展了新型治疗性抗凝剂适配子/解毒剂对的基本发现。我们认为，将这些药物转化为临床实践的关键下一步是在体外和动物模型中进行预测测试，例如我们将在该项目中使用的模型。这项拟议的工作将揭示这一创新的治疗策略是否能够在血栓前环境中提供优越的抗凝，同时避免诸如出血、血小板功能障碍、全身炎症和伤口愈合受损等不良影响。

Profound and controllable anticoagulation is essential during a large number of clinical procedures including percutaneous and surgical revascularization procedures (PCI and CABG), aortic surgery and other vascular interventions. Immediate anticoagulation therapy is also required in a variety of thrombotic diseases such as acute coronary syndromes, pulmonary embolism or deep vein thrombosis. Significant risks and side effects of all of these interventions and therapies include profound bleeding or thrombosis leading to cerebrovascular or cardiovascular compromise. The clinical and financial implications of these outcomes can be profound and are associated with prolonged hospitalization, reduced quality of life, and increased health-care resource utilization. The proposed work extends the basic discoveries of novel therapeutic anticoagulant aptamer/antidote pairs. We believe that a crucial next step in the translation of these agents to clinical practice is the testing in predictive in vitro and animal models such as those we will employ in this project. The proposed work will reveal whether this innovative therapeutic strategy can provide superior anticoagulation in prothrombotic environments, while avoiding undesired effects such as bleeding, platelet dysfunction, systemic inflammation and impaired wound healing.