THROMBOGENESIS IN BLOOD PUMPING DEVICES

血栓形成和血栓栓塞的风险仍然是主要的植入后 所有与血液接触的器械。试图控制 药物血栓栓塞并不总是成功的，因为 血栓栓塞过程涉及许多因素，其中许多不是 很好理解。影响因素包括器械设计和 所产生的流动模式，所使用的材料，以及 血 与装置相关的血栓栓塞的主要问题是缺乏 监测真实的血栓栓塞事件过程的可用方法 时间目前，治疗是基于临床经验， 纤维蛋白降解产物的循环水平;后者出现在 只有在血栓形成后才能止血。正确使用 抗凝剂/抗血小板剂是成功植入后的关键 患者管理;使用不足的量不能控制血栓形成， 使用过量会导致出血， 问题.血栓栓塞的实时检测将使人们有可能 调整抗血栓药物的剂量至最有效水平， 极大地促进了对患者的适当管理。这也将使 可以直接评估治疗策略， 器械相关血栓栓塞。 在激光散射装置的帮助下， 真实的时间内循环血液中的微栓子和血液过滤 为了评估微栓子闭塞性，申请人已经 证明了血泵中微栓子检测的可行性， 离体动物模型。他们注意到微栓子的释放 器械与循环血液接触后即刻。 最初，释放的栓子是最小闭塞的，但是栓子 在血液-物质接触的时间过程中， 闭塞，即使释放的栓子数量可能减少。的 初始血液中存在治疗浓度的肝素- 材料接触不能阻止栓塞过程。设备是否 在接下来的几个小时内表现出减少的栓塞（可能是由于 表面钝化）或继续形成血栓似乎取决于 在装置设计上（存在静态或其他流动区域 干扰）和表面相关的血液材料相互作用。 申请人提出采用一组能够直接 监测血栓栓塞以研究血泵中的血栓形成 在临床相关条件下，并评估 减少（或预防）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 小牛离体LVAD模型，以确定抗血栓栓塞有效性 三种常用的抗血栓形成药物-肝素， 阿司匹林与肝素，和香豆素-和一个常用的-结果 将在植入后提供重要和直接的临床受益 患者管理，并将有助于了解 血栓栓塞，以帮助血液接触装置的长期发展。

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.