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THROMBOGENESIS IN BLOOD PUMPING DEVICES

泵血装置中的血栓形成

基本信息

批准号：
2459953
负责人：
SYED F MOHAMMAD
金额：
$ 31.11万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-08-01 至 1999-07-31
项目状态：
已结题

项目摘要

The risk of thrombosis and thromboembolization remains a major postimplant concern with all devices that contact blood. Attempts to control thromboembolism with drugs are not always successful because the thromboembolic process involves a number of factors, many of which are not well understood. Contributing factors include the device design and resulting flow patterns, the materials used, and the coagulation state of the blood. A major problem with device-associated thromboembolization is the lack of available methods to monitor the course of thromboembolic events in real time. Currently, treatments are based on clinical experience and the circulating levels of fibrin degradation products; the latter appear in blood only after thrombosis has occurred. Proper use of anticoagulants/antiplatelet agents is critical for successful postimplant patient management; using inadequate amounts fails to control thrombosis, and using excessive amounts leads to bleeding, a frequent postimplant problem. Real-time detection of thromboemboli would make it possible to adjust the dose of antithrombotic agents to the most effective level, thus greatly facilitating proper patient management. It would also make it possible to directly evaluate therapeutic strategies for controlling device-related thromboembolism. With the help of a laser light-scattering device that can detect microemboli in circulating blood in real time and a blood-filtration method to assess microemboli occlusiveness, the applicants have demonstrated the feasibility of microemboli detection in blood pumps in an ex-vivo animal model. They have noted that microemboli are released immediately after a device comes in contact with circulating blood. Initially, the emboli released are minimally-occlusive, but the emboli released later in the time course of blood-material contact are more occlusive, even though the number of emboli released may decrease. The presence of therapeutic concentrations of heparin during initial blood- material contact fails to stop the embolic process. Whether the device exhibits decreasing embolization over the next several hours (perhaps due to surface passivation) or continues to be thrombogenic appears to depend on the device design (the presence of areas of stases or other flow disturbances) and surface-related blood-material interactions. The applicants propose to employ a set of tools capable of directly monitoring thromboemboli to investigate thrombogenesis in blood pumps under clinically-relevant conditions and to evaluate the effectiveness of various available approaches to minimize (or prevent) thrombogenesis. After completing important in-vitro calibration studies, they will use a calf ex-vivo LVAD model to determine the antithromboembolic effectiveness of three commonly-used antithrombotic pharmacologic agents - heparin, aspirin with heparin, and coumadin - and one commonly-used - The results will provide important and immediate clinical benefits in post-implant patient management and will contribute to the understanding of thromboembolism to aid long-term development of blood-contacting devices.

血栓形成和血栓栓塞术的风险仍然是术后的主要因素与所有接触血液的设备有关。试图控制药物血栓栓塞症并不总是成功的，因为血栓形成过程涉及许多因素，其中许多因素并不是很好理解。促成因素包括设备设计和由此产生的流型、所使用的材料和凝聚状态鲜血。设备相关血栓栓塞术的一个主要问题是缺乏可用于实时监测血栓栓塞症事件进程的方法时间到了。目前，治疗方法是根据临床经验和循环中纤维蛋白降解产物的水平；后者出现在只有在血栓形成后才能用血。正确使用抗凝剂/抗血小板药是术后成功的关键病人管理；使用不足的剂量无法控制血栓形成，过量使用会导致出血，这是一种常见的术后出血有问题。血栓栓子的实时检测将使其能够将抗血栓药物的剂量调整到最有效的水平，因此极大地方便了适当的病人管理。它也会让它成为可以直接评估控制疾病的治疗策略设备相关血栓栓塞症。在激光散射装置的帮助下，可以检测到实时循环血液中的微栓子和血液滤过评估微栓子闭塞的方法，申请人有论证了血泵中微栓子检测的可行性体外动物模型。他们注意到微栓子被释放在设备接触到循环中的血液之后。最初，释放的栓子是最小闭塞的，但栓子较晚释放的血液与物质接触的时间进程更多闭塞，即使释放的栓子数量可能会减少。这个初始血液中存在治疗性浓度的肝素- 物质接触不能阻止栓塞过程。该设备是否显示在接下来的几个小时内栓塞率减少(可能是由于表面钝化)或持续血栓形成似乎取决于关于设备设计(堆场或其他流动区域的存在扰动)和与表面有关的血液-材料相互作用。申请人建议使用一套工具，能够直接监测血栓栓子以研究血泵的血栓形成在临床相关条件下，并评估其疗效减少(或防止)血栓形成的各种可用方法。在完成重要的体外校准研究后，他们将使用小牛体外LVAD模型测定抗血栓栓塞剂的疗效三种常用的抗血栓药物--肝素，阿司匹林、肝素和香豆素--以及一种常用的--结果将在植入后提供重要和直接的临床益处患者管理，将有助于理解血栓栓塞症，以帮助血液接触设备的长期发展。