Development of a point of care diagnostic to guide efficient usage of blood produ

描述（由申请人提供）：在美国每年接受心肺旁路（CPB）手术的60万患者中，超过60%的患者经历手术内和术后出血。治疗方案可供选择，每种治疗方案对应于特定的止血缺陷：(a)新鲜冷冻血浆（FFP）纠正血浆凝血蛋白，(b)血小板浓缩物（血小板）恢复血小板，(c)冷冻沉淀恢复纤维蛋白原，(d)抗纤溶药物（减缓溶凝蛋白的活性）。然而，临床证据强烈表明，有针对性地使用这些产品可将死亡率降低2.5倍，心肌梗死降低3倍，肾功能衰竭降低13倍，中风事件降低3.6倍，同时每家医院每年可节省高达400万美元。不幸的是，目前在护理点（POC）还没有全面的止血测试，无法提供关于最佳治疗方案的快速结果。POC提供的测试即使组合使用也不能提供所需的信息。因此，目前的临床实践是反复输血血液制品和主观评价出血。这一过程缓慢且容易输血过量，导致免疫反应、感染和不必要费用的风险增加。建议的解决方案：HemoSonics LLC正在开发一种POC仪器，即HemoSonics全球止血分析仪（HS-GHA），它可以直接量化四种止血成分的功能，从而实现适当的治疗选择。HS-GHA基于超声流变法（SR），这是一种基于超声的新型技术，不仅能够评估凝块时间（取决于血浆凝血蛋白），还能够评估凝块形成速率（取决于纤维蛋白原）、凝块硬度（取决于纤维蛋白原和血小板）和溶解时间（取决于溶块蛋白）。如果证明是成功的，HS-GHA将有助于：(i)外科小组实施正确的治疗；（ii）医院通过减少不必要的输血节省成本；（iii）血库保存血液制品；（iv）改善病人的护理。如果证明SR可以测量止血的4种成分的功能，将建立这种方法的可行性。这项研究是HemoSonics有限责任公司与弗吉尼亚大学生物医学工程系和医学院的合作成果。

DESCRIPTION (provided by applicant): Over 60% of the 600,000 patients undergoing cardio-pulmonary bypass (CPB) procedures in the US each year experience intra- and post-operative bleeding. Treatment options are available, each corresponding to a specific hemostatic defect: (a) fresh frozen plasma (FFP) to correct the plasma coagulation proteins, (b) platelet concentrate to restore platelets, (c) cryoprecipitate to restore fibrinogen, and (d) antifibrinolytics to slow the activity of the clot-dissolving proteins. However, clinical evidence strongly indicates that targeted use of these products can reduce mortality by 2.5X, myocardial infarction by 3X, renal failure by 13X, and stroke events by 3.6X, while producing savings of up to $4M/year per hospital. Unfortunately, there is no global test of hemostasis available at the point of care (POC), which is able to provide rapid results about the best treatment option. The tests that are available at POC can't provide the required information, even if used in combination. Thus, current clinical practice is iterative transfusion of blood products and subjective evaluation of bleeding. This process is slow and prone to over transfusions, resulting in increased risk of immunological reactions, infections, and unnecessary expenses. Proposed Solution: HemoSonics LLC is developing a POC instrument, the HemoSonics Global Hemostasis Analyzer (HS-GHA) that can directly quantify the function of the four hemostatic components, enabling appropriate selection of treatment. The HS-GHA is based on sonorheometry (SR), a novel ultrasound-based technology able to assess not only time to clot (dependent upon the plasma coagulation proteins) but also clot formation rate (dependent upon fibrinogen), clot stiffness (dependent upon fibrinogen and platelets), and time to lysis (dependent upon clot-dissolving proteins). If proven successful, the HS-GHA will help: (i) the surgical team administer the correct treatment, (ii) the hospital save costs by reducing unnecessary transfusions, (iii) the blood bank save blood products, and (iv) improve patient's care. Feasibility of this approach will be established if it is demonstrated that SR can measure the function of the 4 components of hemostasis. This research is a collaborative effort between HemoSonics, LLC and the University of Virginia Department of Biomedical Engineering and School of Medicine. PUBLIC HEALTH RELEVANCE: Clinical evidence strongly indicates that improved management of bleeding with targeted use of blood products can reduce one-year mortality by 2.5X, myocardial infarction by 3X, renal failure by 13X, and stroke events by 3.6X, while producing cost savings of up to $4M/year per hospital. Unfortunately, management of bleeding remains suboptimal due to the limitations of current diagnostic tests. The goal of this proposal is to develop a novel point-of-care (POC) diagnostic instrument that will improve the current management of bleeding and usage of blood products, thus improving patients' outcomes and generating substantial cost savings.