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

描述(申请人提供)：问题：在美国每年接受体外循环(CPB)手术的60万名患者中，超过60%的患者经历了大量出血，这需要输血产品。有四种治疗方法可供选择，每一种都对应于一种特定的止血缺陷：(A)新鲜冰冻血浆(FFP)以纠正血浆凝血因子，(B)浓缩血小板以恢复血小板，(C) 冷沉淀以恢复纤维蛋白原，以及(D)抗纤溶药物以减缓溶解血栓的蛋白质的活性。然而，临床文献强烈表明，随着血液制品使用的增加，发病率和死亡风险以剂量依赖的方式增加。据估计，每输血一次，术后严重感染的几率增加76%，心脏发病率增加55%，神经系统发病率增加39%，住院总死亡率增加77%。此外，术后每单位输血的住院天数增加0.82天。与此同时，有针对性地使用这些产品可以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，即 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。这一过程缓慢，而且容易过度输血，导致结果恶化和不必要费用的风险增加。HemoSonics提出的解决方案：HemoSonics LLC正在开发一种POC仪器，即全球止血分析仪(GHA)，该仪器可以量化四种止血成分的功能，使正确选择治疗成为可能。GHA基于超声流变仪(SR)，这是一项新技术，不仅能够评估凝块形成时间(取决于血浆凝血因子)，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(取决于溶解血栓的蛋白)。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) 血库可以保存血液产品，最重要的是(Iv)改善病人护理。建议的SBIR工作：在第一阶段，我们成功地完成了SR测量四种止血成分功能的可行性论证。在第二阶段，我们打算最终完成原型开发并评估其在CPB中的表现，以检验SR可以提供有助于将不必要的输血降至最低、减少总体医疗支出和改善患者预后的信息这一假设。此外，这些研究中获得的数据将用于FDA的监管批准。这项研究是一项合作努力。 血液超音速，弗吉尼亚大学生物医学工程系和医学院，以及弗吉尼亚医学院(弗吉尼亚联邦大学)。

DESCRIPTION (provided by applicant): The Problem: Over 60% of the 600,000 patients undergoing cardio-pulmonary bypass (CPB) procedures in the US each year experience excessive bleeding, which requires transfusions of blood products. There are four treatment options available, each corresponding to a specific hemostatic defect: (a) fresh frozen plasma (FFP) to correct the plasma coagulation factors, (b) platelet concentrate to restore platelets, (c) cryoprecipitate to restore fibrinogen, and (d) anti-fibrinolytics to slow the activity of the clot-dissolving proteins. However, clinical literature strongly indicates that morbidity and mortality risks increase in a dose-dependent way with increased use of blood products. It has been estimated that each unit transfused increases the post-operative odds of severe infection by 76%, cardiac morbidity by 55%, neurological morbidity by 39%, and overall in- hospital mortality by 77%. Furthermore post-operative length of stay increases by 0.82 days per unit transfused. Meanwhile, targeted use of these products can produce 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 worsened outcomes and unnecessary expenses. HemoSonics' Proposed Solution: HemoSonics LLC is developing a POC instrument, the Global Hemostasis Analyzer (GHA) that can quantify the function of the four hemostatic components, enabling correct selection of treatment. The GHA is based on sonorheometry (SR), a novel technology able to assess not only time to clot (dependent upon the plasma coagulation factors) but also clot formation rate (dependent upon fibrinogen), clot stiffness (dependent upon fibrinogen and platelets), and time to lysis (dependent upon clot-dissolving proteins). The 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, most importantly, (iv) improve patient care. Proposed SBIR Work: In Phase I, we successfully completed demonstration of the feasibility of SR to measure the function of the four hemostatic components. In Phase II, we intend to finalize prototype development and evaluate its performance in CPB, in order to test the hypothesis that SR can provide information that will aid in minimizing unnecessary transfusions, reducing overall healthcare spending and improving patient outcomes. Furthermore, data obtained in these studies will be utilized for FDA regulatory approval. This research is a collaborative effort between HemoSonics, the University of Virginia Department of Biomedical Engineering and School of Medicine, and Medical College of Virginia (Virginia Commonwealth University).