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: 10710221
• 负责人: Anahita Dua
• 金额: $ 26.62万
• 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 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10710221
• 关键词: Address; Age; Amputation; Anticoagulants; Anticoagulation; Arteries; Automobile Driving; Biological Assay; Blood Coagulation Factor; Blood Platelets; Blood coagulation; Blood flow; Blood specimen; Bypass; 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; Life; Limb structure; Long-Term Care for Elderly; Lower Extremity; Maps; Measures; Modeling; Operative Surgical Procedures; Patients; Pattern; Peripheral arterial disease; Pharmaceutical Preparations; Pilot Projects; Population; Postoperative Period; Prevalence; Procedures; Research; Risk; Risk Factors; Sampling; Stents; Testing; Thrombelastography; Thrombin; Thrombophilia; Thrombosis; Time; Time trend; Vascularization; Vulnerable Populations; Whole Blood; aged; artery occlusion; 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; predictive tools; 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.

旁路移植物和/或支架血栓形成导致下肢血流丧失是导致下肢血流减少的主要原因 老年患者（年龄≥60岁）截肢的发生率高达17%。 患者的 1 年死亡率高达 50%；因此，预防移植物/支架血栓形成至关重要。 导致移植物/支架血栓形成的常见病因是高凝状态（凝血倾向增加）。 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，但是 管理老年患者的血栓预防具有挑战性，因为他们的生命和健康风险都很高 威胁血栓和出血；因此，有针对性的、及时的抗凝治疗尤其重要。 对于血流受损的四肢进行血运重建手术后，这些患者的高凝状态很重要。 可能是暂时的，因此目前的标准做法是开始抗凝治疗以对抗暂时性血栓 倾向会增加术后几个月内出血的风险，目前尚无办法。 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 指导有针对性的、安全的抗凝治疗因此，该提案的目标是定义客观的、个体化的。 识别血栓形成高风险老年患者并指导血栓预防策略以改善的指标 我们的初步数据显示，护理点凝血测试可以识别短暂的情况。 凝血状态的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）和血小板图（PM）确定了 这些发现超越了先前的研究，表明血栓事件之前的高凝状态。 纵向获取个人的多个自动测量值（每个时间点的单个血液样本） 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 存在移植物血栓形成风险，以及当风险最高时，以改善长期临床护理。 结合临床变量，这样的工具可以实现早期、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。 研究结果表明，我们结合纵向凝血测定（TEG/血小板图谱/凝血酶 一代）与风险预测模型中的临床变量将能够识别哪些老年患者 该项目的目的是： (1) 确定个体的高凝状态模式。 有肢体移植物/支架血栓形成风险的老年患者，以描绘出凝血功能亢进的成分 (2) 开发并验证一种新颖的个性化肢体移植/支架风险预测工具 研究结果将产生一种新型的、个体化的风险预测工具，可以识别老年患者的血栓形成。 移植物/支架肢体血栓高危老年患者并指导临床决策以改善 针对这一弱势群体的安全有效的血栓预防策略。

项目成果

Atorvastatin Effect on Clopidogrel Efficacy in Patients with Peripheral Artery Disease.

阿托伐他汀对周围动脉疾病患者氯吡格雷疗效的影响。

• 发表时间: 2023-09
• 影响因子: 1.5
• 作者: Suarez Ferreira, Sasha P;Hall, Ryan P;Majumdar, Monica;Goudot, Guillaume;Jessula, Samuel;Bellomo, Tiffany;Lee, Ivy;Kukreja, Navi;Parmar, Gaurav;Boada, Ana E;Dua, Anahita
• 通讯作者: Dua, Anahita

Predicting Arterial Thrombotic Events Following Peripheral Revascularization Using Objective Viscoelastic Data.

使用客观粘弹性数据预测外周血运重建后的动脉血栓事件。

• 发表时间: 2023-01-03
• 影响因子: 5.4
• 作者: Majumdar, Monica;Hall, Ryan P;Feldman, Zachary;Goudot, Guillaume;Sumetsky, Natalie;Jessula, Samuel;Kirshkaln, Amanda;Bellomo, Tiffany;Chang, David;Cardenas, Jessica;Patell, Rushad;Eagleton, Matthew;Dua, Anahita
• 通讯作者: Dua, Anahita