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

通过开发风险预测工具预防老年人移植物血栓形成

• 批准号: 10590991
• 负责人: Anahita Dua
• 金额: $ 21万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10590991
• 关键词: Address; Amputation; Anticoagulants; Anticoagulation; Arteries; Automobile Driving; Biological Assay; Blood Coagulation Factor; Blood Platelets; Blood coagulation; Blood flow; Blood specimen; Bypass; Caring; Cessation of life; Chronic; Clinical; Coagulation Process; Dangerousness; Data; Data Set; Development; Elderly; Etiology; Event; Fibrinolysis; Generations; Goals; Hemorrhage; Hyperactivity; Impairment; Incidence; Individual; Intervention; Intrinsic factor; Lead; Life; Limb structure; Lower Extremity; Measures; Medication Management; Modeling; Operative Surgical Procedures; Patients; Pattern; Peripheral arterial disease; Pharmaceutical Preparations; Pilot Projects; Population; Postoperative Period; Prevalence; Procedures; Research; Risk; Risk Factors; Stents; Testing; Thrombelastography; Thrombin; Thrombophilia; Thrombosis; Time; Time trend; Vulnerable Populations; Whole Blood; aged; artery occlusion; base; blood perfusion; clinical care; clinical decision-making; cohort; combat; high risk; improved; limb amputation; mortality; novel; novel strategies; older patient; overtreatment; personalized risk prediction; point of care; prevent; prospective; revascularization surgery; risk prediction; risk prediction model; stent thrombosis; targeted treatment; thrombotic; thrombotic complications; tool

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.

绕过移植物和/或支架血栓形成导致血液流失到下肢是主要原因 古老的患者（≥60岁）的截肢术，其事件高达17％。这些截肢 患者的死亡率高达50％；因此，防止移植物/支架血栓形成至关重要。最多 常见的病因驱动移植物/支架血栓形成是高凝性（增加血液凝结的希望）。 当前预防移植物/支架血栓形成的策略依赖于抗血小板和抗凝药物，但 在古老的患者中管理血栓预防是具有挑战性的 威胁血栓形成和出血；因此，尤其是针对性的及时抗凝剂处方 重要的。手术后这些患者的高凝性使血流量受损的四肢血流 可以是短暂的，因此目前开始抗凝抗凝以应对临时血栓形成的标准做法 倾向增加了后期几个月的出血风险。目前没有办法 准确预测哪些老年患者在limb血运重建后的某个时间点有血栓形成风险 指南有针对性的，安全的抗凝治疗。因此，该提议的目的是定义目标，个性化 指标可以识别老年患者的血栓形成风险高，并指导血栓预防策略以改善 老患者的照顾。我们的初步数据表明，护理点凝血测试可以识别瞬态 凝血状态的升高在发生移植血栓形成的老年患者中被唯一放大。 此外，全血栓塑料学（TEG）和血小板映射（PM）确定了 血栓事件之前的高凝性。这些发现通过证明 纵向获得个体的多个自动措施（以单个时间点为单一的血液样本） 凝血参数并将其纳入风险评分工具中可以帮助预测哪些老年患者是 有接枝血栓形成的风险，以及它们处于最高风险时，可以改善和长期临床护理。什么时候 结合临床变量，这种工具可以使早期的，有针对性的抗凝干预措施可以 防止衣服并发症，从而降低截肢和死亡的风险。基于这些小说 调查结果，我们假设结合纵向凝血测定法（TEG/血小板映射/凝血酶 在风险预测模型中具有临床变量的生成）可以鉴定老年患者 移植血栓形成的风险。该项目的目的是：（1）确定个人超凝性模式 具有肢体移植物/支架血栓形成风险的老年患者描绘凝结的多动成分 级联; （2）开发和验证一种新颖和个性化的风险预测工具，用于极端移植/支架 老患者的血栓形成。结果将产生一种新颖的个性化风险预测工具，可以识别 老年患者患有移植物/支架肢体血栓形成和指导临床决策以改善的老年患者 为这一脆弱人群的安全有效的血栓预防策略。