Preventing Graft Thrombosis in the Elderly through Development of a Risk Prediction Tool

旁路移植物和/或支架血栓形成导致流向下肢的血流损失是导致下肢缺血的主要原因。 老年患者（年龄≥60岁）截肢率高达17%。这些被截肢的老人 患者的1年死亡率高达50%;因此，预防移植物/支架血栓形成是至关重要的。最 驱动移植物/支架血栓形成的常见病因是高凝性（增加的血液凝固倾向）。 目前预防移植物/支架血栓形成的策略依赖于抗血小板和抗凝药物，但 在老年患者中进行血栓预防是具有挑战性的，因为他们具有高的相反的生命风险， 威胁血栓形成和出血;因此，有针对性的，及时的抗凝剂处方，特别是 重要.这些患者在血流受损的肢体血运重建手术后的高凝状态 可能是短暂的，因此目前开始抗凝治疗以对抗暂时性血栓形成的标准做法是 倾向增加了术后数月内出血的风险。目前还没有办法 准确预测哪些老年患者在肢体血运重建后的某个时间点有血栓形成的风险， 指导靶向、安全的抗凝治疗。因此，本提案的目标是确定客观、个性化的 识别血栓形成高风险老年患者的指标，并指导血栓预防策略， 照顾老年病人。我们的初步数据显示，即时凝血试验可以识别短暂的 凝血状态升高，在发生移植物血栓形成的老年患者中尤为明显。 此外，全血血栓弹力图（TEG）和血小板绘图（PM）确定了 血栓形成事件之前的高凝状态。这些发现超越了先前的研究，表明， 纵向采集个体的多个自动测量（在每个时间点的单个血液样本中）， 凝血参数并将其纳入风险评分工具可以帮助预测哪些老年患者 在移植物血栓形成的风险，当他们处于最高风险，以改善和长期的临床护理。当 结合临床变量，这种工具可以实现早期，有针对性的抗凝干预， 预防凝血并发症，从而降低截肢和死亡的风险。根据这些小说 研究结果，我们假设结合纵向凝血试验（TEG/血小板绘图/凝血酶 风险预测模型中的临床变量将能够识别 移植物血栓形成的风险。本研究的目的是：（1）识别个体高凝模式， 有肢体移植物/支架血栓形成风险的老年患者，以描述凝血的高活性成分 级联;和（2）开发并验证肢体移植物/支架的新型个性化风险预测工具 老年患者血栓形成。研究结果将产生一种新颖的、个性化的风险预测工具， 移植物/支架肢体血栓形成高风险的老年患者，并指导临床决策，以改善 安全有效的血栓预防策略。

Bypass graft and/or stent thrombosis resulting in loss of blood flow to the lower extremity is a leading cause of amputation in elderly patients (aged ≥60 years), with an incidence of up to 17%. These amputated elderly patients suffer 1-year mortality as high as 50%; hence, preventing graft/stent thrombosis is critical. The most common etiology driving graft/stent thrombosis is hypercoagulability (increased blood clotting propensity). Current strategies to prevent graft/stent thrombosis rely on anti-platelet and anticoagulant medications, but managing thromboprophylaxis in elderly patients is challenging as they have high opposing risks of both life- threatening thrombosis and hemorrhage; therefore, targeted, timely anticoagulant-prescribing is especially important. Hypercoagulability in these patients after surgery to revascularize extremities with impaired blood flow can be transient, so the current standard practice of starting anticoagulation to combat temporary thrombotic propensity increases the risk of hemorrhage during the months post-procedure. There is presently no way to accurately predict which elderly patients are at risk of thrombosis at a point in time post-limb revascularization to guide targeted, safe anticoagulation therapy. Hence, the goal of this proposal is to define objective, individualized metrics to identify elderly patients at high risk of thrombosis and guide thromboprophylaxis strategies to improve the care of elderly patients. Our preliminary data reveal that point-of-care coagulation tests can identify transient elevations of coagulation status that are uniquely amplified among elderly patients who develop graft thrombosis. Furthermore, whole-blood thromboelastography (TEG) and platelet mapping (PM) identified the onset of hypercoagulability prior to a thrombotic event. These findings advance beyond prior research by showing that longitudinally acquiring multiple automated measures (in a single blood sample per time point) of individuals' coagulation parameters and incorporating them into risk-scoring tools can help predict which elderly patients are at risk of graft thrombosis, and when they are at highest risk, to improve and long-term clinical care. When combined with clinical variables, such a tool could enable early, targeted anticoagulant intervention that can prevent clotting complications, thereby reducing the risks of amputation and death. Based on these novel findings, we hypothesize that combining longitudinal coagulation assays (TEG/platelet mapping/thrombin generation) with clinical variables in a risk-prediction model will enable identification of elderly patients who are risk of graft thrombosis. The aims of this project are to: (1) Identify individual hypercoagulability patterns among elderly patients at risk of extremity graft/stent thrombosis to delineate hyperactive components of the coagulation cascade; and (2) Develop and validate a novel and personalized risk prediction tool for extremity graft/stent thrombosis in elderly patients. The results will yield a novel, individualized risk-prediction tool that can identify elderly patients at high risk for graft/stent extremity thrombosis and guide clinical decision-making to improve safe and effective thromboprophylaxis strategies for this vulnerable population.