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

旁路移植和/或支架血栓形成导致血液流向下肢的损失是一个主要原因

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.