The Role of Coagulation Factor XII in Medical Device-induced Thrombosis

凝血因子 XII 在医疗器械引起的血栓形成中的作用

• 批准号: 10311464
• 负责人: Novella Bates
• 金额: $ 3.7万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-20 至 2022-06-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311464
• 关键词: Role; Coagulation; Factor; XII; Medical

Project Summary Blood-contacting medical devices, such as catheters, vascular grafts, and stents, are often required to treat cardiovascular diseases. A major cause of device failure is intraluminal blood clot formation, also known as thrombus formation or thrombosis. Thrombosis hinders blood flow and can lead to myocardial infarction or stroke, due to tissue death. Anticoagulants are used to prevent and reduce the incidence of thrombosis on medical devices. However, current therapies target important hemostatic factors, which often leads to detrimental bleeding side effects. Factor (F) XII is a coagulation factor that has been implicated in thrombosis, but has no known role in hemostasis. Therefore, it has been suggested FXII could be a safe target for the next-generation of anticoagulants and this has been supported by early studies. Despite the promise of FXII-targeted therapies, the mechanisms of FXII activation that lead to thrombosis on cardiovascular medical devices remain unknown. I hypothesize that thrombosis on medical devices is dependent on FXIIa-fibrin and FXII-platelet interactions at the blood-device interface. The proposed work aims to (1) determine the role of FXIIa in the modulation of fibrin formation and structure in medical device-induced thrombosis and (2) determine the role of device-activated platelets on FXII activation in medical device-induced thrombosis. Determining how FXII activation promotes thrombosis on medical devices will aid in the development of effective and safe FXII-targeted anticoagulants. FXII specific anticoagulants could reduce or eliminate morbidity and mortality in patients suffering from medical device-related thrombosis. The proposed work will investigate interactions between FXII and major components of a thrombus on medical device materials.

项目摘要 通常需要接触血液的医疗器械，如导管、血管移植物和支架来治疗 心血管疾病器械失效的主要原因是腔内血凝块形成，也称为血栓形成。 血栓形成或血栓形成。血栓形成阻碍血液流动并可导致心肌梗塞或中风， 因为组织死亡。抗凝剂用于预防和减少血栓形成的发生， 装置.然而，目前的疗法靶向重要的止血因子，这通常导致有害的止血作用。 出血的副作用因子（F）XII是一种与血栓形成有关的凝血因子，但不具有 已知止血作用。因此，有人建议FXII可能是下一代的安全目标 这一点得到了早期研究的支持。尽管FXII靶向治疗有希望， 导致心血管医疗装置上血栓形成的FXII激活机制仍然未知。 我假设医疗器械上的血栓形成依赖于FXIIa-纤维蛋白和FXII-血小板相互作用， 血液设备接口本研究的目的是：（1）确定FXIIa在调节纤维蛋白中的作用， 形成和结构在医疗器械引起的血栓形成和（2）确定设备激活的作用 血小板对医疗器械诱导血栓形成中FXII活化的影响。确定FXII激活如何促进 在医疗器械上预防血栓形成将有助于开发有效和安全的靶向FXII的抗凝剂。 FXII特异性抗凝剂可以减少或消除患有医学疾病的患者的发病率和死亡率。 器械相关血栓形成。拟议的工作将调查FXII和主要成分之间的相互作用 医疗器械材料上的血栓。