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

描述(由申请人提供)：在美国每年接受体外循环(CPB)手术的60万名患者中，超过60%的患者经历了术中和术后出血。有多种治疗方案可供选择，每种方案对应于一种特定的止血缺陷：(A)新鲜冰冻血浆(FFP)用于纠正血浆凝血蛋白；(B)浓缩血小板用于恢复血小板；(C)冷沉淀用于恢复纤维蛋白原；以及(D)抗纤溶药物用于减缓溶解血栓的蛋白的活性。然而，临床证据有力地表明，有针对性地使用这些产品可以将死亡率降低2.5倍，心肌梗死减少3倍，肾功能衰竭减少13倍，中风事件减少3.6倍，同时为每家医院每年节省高达400万美元。不幸的是，在护理点(POC)没有可用的全球止血测试，它能够提供关于最佳治疗方案的快速结果。POC提供的测试无法提供所需信息，即使组合使用也是如此。因此，目前的临床实践是反复输血和主观评估出血。这个过程很慢，而且容易过度输血，导致免疫反应、感染和不必要的费用增加的风险。建议的解决方案：HemoSonics LLC正在开发一种POC仪器--HemoSonics全球止血分析仪(HS-GHA)，该仪器可以直接量化四种止血成分的功能，使适当的治疗选择成为可能。HS-GHA基于超声流变仪(SR)，这是一项基于超声的新技术，不仅能够评估凝块形成时间(取决于血浆凝血蛋白)，还能够评估凝块形成率(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(取决于溶解凝块的蛋白)。如果证明成功，HS-GHA将帮助：(I)外科团队实施正确的治疗，(Ii)医院通过减少不必要的输血来节省成本，(Iii)血库保存血液产品，以及(Iv)改善患者的护理。如果证明SR可以测量止血的4种成分的功能，则该方法的可行性将被证实。这项研究是HemoSonics，LLC和弗吉尼亚大学生物医学工程系和医学院的合作成果。 与公共卫生相关：临床证据有力地表明，通过有针对性地使用血液产品来改善出血管理，可以将一年死亡率降低2.5倍，心肌梗死减少3倍，肾功能衰竭减少13倍，中风事件减少3.6倍，同时每家医院每年可节省高达400万美元的成本。不幸的是，由于目前诊断测试的局限性，出血的处理仍然不是最理想的。这项提议的目标是开发一种新型的护理点(POC)诊断仪器，该仪器将改善目前对出血和血液产品使用的管理，从而改善患者的预后并节省大量成本。

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.